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Migraines linked to higher risk of dementia
, according to research published online Sept. 4 in the International Journal of Geriatric Psychiatry.
In the Manitoba Study of Health and Aging, a population-based, prospective cohort study, 679 community-dwelling adults with a mean age of 75.9 years were followed for 5 years. Participants screened as cognitively intact at baseline had complete data on migraine history and all covariates at baseline and were assessed for cognitive outcomes 5 years later.
The study showed that a history of migraines was associated with a 2.97-fold greater likelihood of dementia, after adjustment for age, education, and a history of stroke, compared with individuals without a history of migraine. Individuals with Alzheimer’s disease were more than four times more likely to have a history of migraines (odds ratio 4.22).
However, researchers found no significant association between vascular dementia and a history of migraines, either before or after adjusting for confounders but particularly after incorporating a history of stroke into the model.
Lead investigator Suzanne L. Tyas, PhD, associate professor in the School of Public Health and Health Systems at the University of Waterloo, Ont., and coauthors suggested that the association between migraine and dementia was largely driven by the strong association between migraines and Alzheimer’s disease.
“This interpretation is supported by the weaker association for dementia than for Alzheimer’s disease, reflecting a dilution of the association with migraines across all types of dementia including vascular dementia, where a significant association was not found,” the researchers wrote.
The study population was 61.9% female, and no men reporting a history of migraine were diagnosed with dementia. While the study reflected a strong association between migraine and dementia in women, the researchers said they were unable to assess potential gender differences in this association.
Commenting on possible mechanisms behind the association, the authors wrote that there were overlaps underlying the biological mechanisms of migraine and dementia. Vascular risk factors such as diabetes, hypertension, heart attack, and stroke are associated with the development of dementia, and a relationship of these risk factors and migraine also has been seen.
“Many of the mechanisms involved in migraine neurophysiology, such as inflammation and reduced cerebral blood flow, are also underlying causes of dementia,” they wrote. “Repeated activation of these pathways in chronic migraineurs has been shown to cause permanent neurological and vascular damage.”
They also observed that the association could be influenced by genetic factors, as individuals with presenilin-1 mutations, which predispose them to Alzheimer’s disease, are more likely to experience migraines or recurrent headaches.
They suggested their findings could inform preventive strategies and treatments for Alzheimer’s disease, as well as interventions such as earlier screening for cognitive decline in individuals who experience migraines.
The study was funded by Manitoba Health and the National Health Research and Development Program of Health Canada. No conflicts of interest were declared.
SOURCE: Morton R et al. Int J Geriatr Psychiatry, 2019 Sep 4. doi: 10.1002/gps.5180.
, according to research published online Sept. 4 in the International Journal of Geriatric Psychiatry.
In the Manitoba Study of Health and Aging, a population-based, prospective cohort study, 679 community-dwelling adults with a mean age of 75.9 years were followed for 5 years. Participants screened as cognitively intact at baseline had complete data on migraine history and all covariates at baseline and were assessed for cognitive outcomes 5 years later.
The study showed that a history of migraines was associated with a 2.97-fold greater likelihood of dementia, after adjustment for age, education, and a history of stroke, compared with individuals without a history of migraine. Individuals with Alzheimer’s disease were more than four times more likely to have a history of migraines (odds ratio 4.22).
However, researchers found no significant association between vascular dementia and a history of migraines, either before or after adjusting for confounders but particularly after incorporating a history of stroke into the model.
Lead investigator Suzanne L. Tyas, PhD, associate professor in the School of Public Health and Health Systems at the University of Waterloo, Ont., and coauthors suggested that the association between migraine and dementia was largely driven by the strong association between migraines and Alzheimer’s disease.
“This interpretation is supported by the weaker association for dementia than for Alzheimer’s disease, reflecting a dilution of the association with migraines across all types of dementia including vascular dementia, where a significant association was not found,” the researchers wrote.
The study population was 61.9% female, and no men reporting a history of migraine were diagnosed with dementia. While the study reflected a strong association between migraine and dementia in women, the researchers said they were unable to assess potential gender differences in this association.
Commenting on possible mechanisms behind the association, the authors wrote that there were overlaps underlying the biological mechanisms of migraine and dementia. Vascular risk factors such as diabetes, hypertension, heart attack, and stroke are associated with the development of dementia, and a relationship of these risk factors and migraine also has been seen.
“Many of the mechanisms involved in migraine neurophysiology, such as inflammation and reduced cerebral blood flow, are also underlying causes of dementia,” they wrote. “Repeated activation of these pathways in chronic migraineurs has been shown to cause permanent neurological and vascular damage.”
They also observed that the association could be influenced by genetic factors, as individuals with presenilin-1 mutations, which predispose them to Alzheimer’s disease, are more likely to experience migraines or recurrent headaches.
They suggested their findings could inform preventive strategies and treatments for Alzheimer’s disease, as well as interventions such as earlier screening for cognitive decline in individuals who experience migraines.
The study was funded by Manitoba Health and the National Health Research and Development Program of Health Canada. No conflicts of interest were declared.
SOURCE: Morton R et al. Int J Geriatr Psychiatry, 2019 Sep 4. doi: 10.1002/gps.5180.
, according to research published online Sept. 4 in the International Journal of Geriatric Psychiatry.
In the Manitoba Study of Health and Aging, a population-based, prospective cohort study, 679 community-dwelling adults with a mean age of 75.9 years were followed for 5 years. Participants screened as cognitively intact at baseline had complete data on migraine history and all covariates at baseline and were assessed for cognitive outcomes 5 years later.
The study showed that a history of migraines was associated with a 2.97-fold greater likelihood of dementia, after adjustment for age, education, and a history of stroke, compared with individuals without a history of migraine. Individuals with Alzheimer’s disease were more than four times more likely to have a history of migraines (odds ratio 4.22).
However, researchers found no significant association between vascular dementia and a history of migraines, either before or after adjusting for confounders but particularly after incorporating a history of stroke into the model.
Lead investigator Suzanne L. Tyas, PhD, associate professor in the School of Public Health and Health Systems at the University of Waterloo, Ont., and coauthors suggested that the association between migraine and dementia was largely driven by the strong association between migraines and Alzheimer’s disease.
“This interpretation is supported by the weaker association for dementia than for Alzheimer’s disease, reflecting a dilution of the association with migraines across all types of dementia including vascular dementia, where a significant association was not found,” the researchers wrote.
The study population was 61.9% female, and no men reporting a history of migraine were diagnosed with dementia. While the study reflected a strong association between migraine and dementia in women, the researchers said they were unable to assess potential gender differences in this association.
Commenting on possible mechanisms behind the association, the authors wrote that there were overlaps underlying the biological mechanisms of migraine and dementia. Vascular risk factors such as diabetes, hypertension, heart attack, and stroke are associated with the development of dementia, and a relationship of these risk factors and migraine also has been seen.
“Many of the mechanisms involved in migraine neurophysiology, such as inflammation and reduced cerebral blood flow, are also underlying causes of dementia,” they wrote. “Repeated activation of these pathways in chronic migraineurs has been shown to cause permanent neurological and vascular damage.”
They also observed that the association could be influenced by genetic factors, as individuals with presenilin-1 mutations, which predispose them to Alzheimer’s disease, are more likely to experience migraines or recurrent headaches.
They suggested their findings could inform preventive strategies and treatments for Alzheimer’s disease, as well as interventions such as earlier screening for cognitive decline in individuals who experience migraines.
The study was funded by Manitoba Health and the National Health Research and Development Program of Health Canada. No conflicts of interest were declared.
SOURCE: Morton R et al. Int J Geriatr Psychiatry, 2019 Sep 4. doi: 10.1002/gps.5180.
FROM THE INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
Is serum serotonin level associated with risk of seizure-related breathing dysfunction?
, according to research published online Sept. 4 in Neurology. The change in serotonin level may reflect physiologic changes that protect against harmful processes that promote sudden unexpected death in epilepsy (SUDEP), the authors wrote.
“Our results give new insight into a possible link between serotonin levels and breathing during and after seizure,” Samden D. Lhatoo, MD, professor of neurology at McGovern Medical School at the University of Texas Health Science Center in Houston, said in a press release. “This may give hope that perhaps someday new therapies could be developed that may help prevent SUDEP. However, our study was small, and much more research is needed to confirm our findings in larger groups before any treatment decisions can be made. It is also important to note that excess serotonin can be harmful, so we strongly recommend against anyone trying to find ways to increase their serotonin levels in response to our study findings.”
Animal and human studies have indicated that breathing dysfunction related to SUDEP may involve serotonergic pathways. Compared with controls, patients with SUDEP have fewer midline serotonergic neurons. Furthermore, a 2018 study suggested an association between severe seizures and decreased serotonergic tone in the postictal state.
Dr. Lhatoo and colleagues examined a prospective cohort of patients with intractable epilepsy to understand the relationship between serum serotonin levels, ictal central apnea (ICA), and postconvulsive central apnea (PCCA). Patients were aged 18 years or older, were admitted to the epilepsy monitoring unit from January 2015 to April 2018, and agreed to take part in an investigation of SUDEP biomarkers. Dr. Lhatoo and colleagues evaluated video EEG, plethysmography, capillary oxygen saturation, and ECG for 49 patients. After a patient had a clinical seizure, the researchers collected postictal and interictal venous blood samples from him or her to measure serum serotonin levels. They classified seizures using the International League Against Epilepsy 2017 seizure classification. Dr. Lhatoo and colleagues analyzed 49 seizures with and without ICA and 27 generalized convulsive seizures with and without PCCA.
Of the 49 patients, 29 were female. Participants’ mean age was 42 years, mean age at epilepsy onset was 25.2 years, and mean epilepsy duration was 16.8 years. The population’s mean body mass index was 28.9. Dr. Lhatoo and colleagues observed ICA in 17 of 49 (34.7%) seizures and PCCA in 8 of 27 (29.6%) seizures.
Postictal serum serotonin levels were significantly higher than interictal levels for seizures without ICA, but not for seizures with ICA. Among patients with generalized convulsive seizures without PCCA, serum serotonin levels were significantly increased postictally, compared with interictal levels, but not among patients with seizures with PCCA. The change in postictal and interictal serotonin levels also differed significantly between participants with and without PCCA. In patients without PCCA, an increase in serotonin was associated with an increase in heart rate, but not in patients with PCCA.
“Large postictal increases in serum serotonin may play a role in modulation of respiration in these patients,” wrote Dr. Lhatoo and colleagues. “Alternatively, the increase in serum serotonin that we measured may be a surrogate for an increase in brain serotonin levels that may depend on similar physiologic mechanisms, rather than serum serotonin directly stimulating breathing.” Low levels of postictal serum serotonin are associated with potentially harmful breathing phenomena that should be investigated in larger studies, the investigators concluded.
The study was funded by a grant from the National Institutes of Health. One author received a laboratory research grant from Zogenix.
SOURCE: Murugesan A et al. Neurology. 2019 Sep 3. doi: 10.1212/WNL.0000000000008244.
, according to research published online Sept. 4 in Neurology. The change in serotonin level may reflect physiologic changes that protect against harmful processes that promote sudden unexpected death in epilepsy (SUDEP), the authors wrote.
“Our results give new insight into a possible link between serotonin levels and breathing during and after seizure,” Samden D. Lhatoo, MD, professor of neurology at McGovern Medical School at the University of Texas Health Science Center in Houston, said in a press release. “This may give hope that perhaps someday new therapies could be developed that may help prevent SUDEP. However, our study was small, and much more research is needed to confirm our findings in larger groups before any treatment decisions can be made. It is also important to note that excess serotonin can be harmful, so we strongly recommend against anyone trying to find ways to increase their serotonin levels in response to our study findings.”
Animal and human studies have indicated that breathing dysfunction related to SUDEP may involve serotonergic pathways. Compared with controls, patients with SUDEP have fewer midline serotonergic neurons. Furthermore, a 2018 study suggested an association between severe seizures and decreased serotonergic tone in the postictal state.
Dr. Lhatoo and colleagues examined a prospective cohort of patients with intractable epilepsy to understand the relationship between serum serotonin levels, ictal central apnea (ICA), and postconvulsive central apnea (PCCA). Patients were aged 18 years or older, were admitted to the epilepsy monitoring unit from January 2015 to April 2018, and agreed to take part in an investigation of SUDEP biomarkers. Dr. Lhatoo and colleagues evaluated video EEG, plethysmography, capillary oxygen saturation, and ECG for 49 patients. After a patient had a clinical seizure, the researchers collected postictal and interictal venous blood samples from him or her to measure serum serotonin levels. They classified seizures using the International League Against Epilepsy 2017 seizure classification. Dr. Lhatoo and colleagues analyzed 49 seizures with and without ICA and 27 generalized convulsive seizures with and without PCCA.
Of the 49 patients, 29 were female. Participants’ mean age was 42 years, mean age at epilepsy onset was 25.2 years, and mean epilepsy duration was 16.8 years. The population’s mean body mass index was 28.9. Dr. Lhatoo and colleagues observed ICA in 17 of 49 (34.7%) seizures and PCCA in 8 of 27 (29.6%) seizures.
Postictal serum serotonin levels were significantly higher than interictal levels for seizures without ICA, but not for seizures with ICA. Among patients with generalized convulsive seizures without PCCA, serum serotonin levels were significantly increased postictally, compared with interictal levels, but not among patients with seizures with PCCA. The change in postictal and interictal serotonin levels also differed significantly between participants with and without PCCA. In patients without PCCA, an increase in serotonin was associated with an increase in heart rate, but not in patients with PCCA.
“Large postictal increases in serum serotonin may play a role in modulation of respiration in these patients,” wrote Dr. Lhatoo and colleagues. “Alternatively, the increase in serum serotonin that we measured may be a surrogate for an increase in brain serotonin levels that may depend on similar physiologic mechanisms, rather than serum serotonin directly stimulating breathing.” Low levels of postictal serum serotonin are associated with potentially harmful breathing phenomena that should be investigated in larger studies, the investigators concluded.
The study was funded by a grant from the National Institutes of Health. One author received a laboratory research grant from Zogenix.
SOURCE: Murugesan A et al. Neurology. 2019 Sep 3. doi: 10.1212/WNL.0000000000008244.
, according to research published online Sept. 4 in Neurology. The change in serotonin level may reflect physiologic changes that protect against harmful processes that promote sudden unexpected death in epilepsy (SUDEP), the authors wrote.
“Our results give new insight into a possible link between serotonin levels and breathing during and after seizure,” Samden D. Lhatoo, MD, professor of neurology at McGovern Medical School at the University of Texas Health Science Center in Houston, said in a press release. “This may give hope that perhaps someday new therapies could be developed that may help prevent SUDEP. However, our study was small, and much more research is needed to confirm our findings in larger groups before any treatment decisions can be made. It is also important to note that excess serotonin can be harmful, so we strongly recommend against anyone trying to find ways to increase their serotonin levels in response to our study findings.”
Animal and human studies have indicated that breathing dysfunction related to SUDEP may involve serotonergic pathways. Compared with controls, patients with SUDEP have fewer midline serotonergic neurons. Furthermore, a 2018 study suggested an association between severe seizures and decreased serotonergic tone in the postictal state.
Dr. Lhatoo and colleagues examined a prospective cohort of patients with intractable epilepsy to understand the relationship between serum serotonin levels, ictal central apnea (ICA), and postconvulsive central apnea (PCCA). Patients were aged 18 years or older, were admitted to the epilepsy monitoring unit from January 2015 to April 2018, and agreed to take part in an investigation of SUDEP biomarkers. Dr. Lhatoo and colleagues evaluated video EEG, plethysmography, capillary oxygen saturation, and ECG for 49 patients. After a patient had a clinical seizure, the researchers collected postictal and interictal venous blood samples from him or her to measure serum serotonin levels. They classified seizures using the International League Against Epilepsy 2017 seizure classification. Dr. Lhatoo and colleagues analyzed 49 seizures with and without ICA and 27 generalized convulsive seizures with and without PCCA.
Of the 49 patients, 29 were female. Participants’ mean age was 42 years, mean age at epilepsy onset was 25.2 years, and mean epilepsy duration was 16.8 years. The population’s mean body mass index was 28.9. Dr. Lhatoo and colleagues observed ICA in 17 of 49 (34.7%) seizures and PCCA in 8 of 27 (29.6%) seizures.
Postictal serum serotonin levels were significantly higher than interictal levels for seizures without ICA, but not for seizures with ICA. Among patients with generalized convulsive seizures without PCCA, serum serotonin levels were significantly increased postictally, compared with interictal levels, but not among patients with seizures with PCCA. The change in postictal and interictal serotonin levels also differed significantly between participants with and without PCCA. In patients without PCCA, an increase in serotonin was associated with an increase in heart rate, but not in patients with PCCA.
“Large postictal increases in serum serotonin may play a role in modulation of respiration in these patients,” wrote Dr. Lhatoo and colleagues. “Alternatively, the increase in serum serotonin that we measured may be a surrogate for an increase in brain serotonin levels that may depend on similar physiologic mechanisms, rather than serum serotonin directly stimulating breathing.” Low levels of postictal serum serotonin are associated with potentially harmful breathing phenomena that should be investigated in larger studies, the investigators concluded.
The study was funded by a grant from the National Institutes of Health. One author received a laboratory research grant from Zogenix.
SOURCE: Murugesan A et al. Neurology. 2019 Sep 3. doi: 10.1212/WNL.0000000000008244.
FROM NEUROLOGY
Key clinical point: Significant increases in serum serotonin after a seizure are associated with lower risk of seizure-related breathing dysfunction.
Major finding: In patients without ictal central apnea, mean interictal serotonin level was 109.1 ng/mL, and postictal levels were 139.8 ng/mL.
Study details: A prospective cohort study of 49 patients with intractable epilepsy.
Disclosures: The study was funded by a grant from the National Institutes of Health. One author received a laboratory research grant from Zogenix.
Source: Murugesan A et al. Neurology. 2019 Sep 3. doi: 10.1212/WNL.0000000000008244.
Blood test may reveal brain injury
researchers reported Aug. 26 in BMJ Paediatrics Open.
“GFAP outperformed UCH-L1 in detecting concussion in both children and adults within 4 hours of injury,” reported lead author Linda Papa, MD, and collaborators. Dr. Papa is an emergency medicine doctor at Orlando Health. “UCH-L1 was expressed at much higher levels than GFAP in those with nonconcussive trauma, particularly in children. Elevations of these biomarkers in nonconcussive head trauma suggest possible subconcussive brain injury. GFAP could be potentially useful to detect concussion for up to a week post injury.”
In 2018 the Food and Drug Administration approved the use of these biomarkers to guide CT scan ordering in adults with mild to moderate traumatic brain injury, but investigators have not established their ability to detect concussion in children or adults. Clinicians lack an objective measure to diagnose concussion acutely.
To assess the ability of GFAP and UCH-L1 to detect concussion, Dr. Papa and colleagues conducted a prospective cohort study. The researchers enrolled trauma patients of all ages at three level I trauma centers in the United States. They included patients with and without head trauma who had a Glasgow Coma Scale score of 15 and who presented within 4 hours of injury. Investigators screened for concussion symptoms, obtained biomarker data from 712 trauma patients, and conducted repeated blood sampling in adults.
They grouped patients by those with concussion (n = 371), those with head trauma without overt signs of concussion (n = 149), and those with peripheral trauma without head trauma or concussion (n = 192). The study included 175 children. Injury mechanisms included car crashes, falls, bicycle accidents, and sports injuries.
Patients with concussion had significantly higher GFAP concentrations, compared with patients with body trauma and patients with nonconcussive head trauma. UCH-L1 levels did not significantly differ between patients with concussion and head trauma controls, however.
“Based on these results, the potential utility of GFAP to distinguish concussion from body trauma controls over 7 days postinjury was fair to excellent,” with area under the receiver operating characteristics curves (AUCs) of 0.75-0.89, the researchers said. “UCH-L1’s ability was guarded and variable with AUCs from poor to good depending on timing of samples.” UCH-L1 demonstrated AUCs that ranged from 0.54 to 0.78; earlier samples performed better.
GFAP elevations in head trauma controls “may represent milder forms of concussion that do not elicit typical signs or symptoms associated with concussion,” the authors wrote. “These injuries may be irrelevant, or they may represent important trauma that is just below the level of clinical detection and referred to as subconcussive trauma. ... Biomarkers (such as GFAP and UCH-L1) could provide a more objective measure of injury and potentially identify those at risk for neurocognitive problems.”
The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Papa is an unpaid scientific consultant for Banyan Biomarkers, which developed kits to measure the biomarkers, and coauthors receive contract research funding from Banyan Biomarkers.
SOURCE: Papa L et al. BMJ Paediatr Open. 2019 Aug 26. doi: 10.1136/bmjpo-2019-000473.
researchers reported Aug. 26 in BMJ Paediatrics Open.
“GFAP outperformed UCH-L1 in detecting concussion in both children and adults within 4 hours of injury,” reported lead author Linda Papa, MD, and collaborators. Dr. Papa is an emergency medicine doctor at Orlando Health. “UCH-L1 was expressed at much higher levels than GFAP in those with nonconcussive trauma, particularly in children. Elevations of these biomarkers in nonconcussive head trauma suggest possible subconcussive brain injury. GFAP could be potentially useful to detect concussion for up to a week post injury.”
In 2018 the Food and Drug Administration approved the use of these biomarkers to guide CT scan ordering in adults with mild to moderate traumatic brain injury, but investigators have not established their ability to detect concussion in children or adults. Clinicians lack an objective measure to diagnose concussion acutely.
To assess the ability of GFAP and UCH-L1 to detect concussion, Dr. Papa and colleagues conducted a prospective cohort study. The researchers enrolled trauma patients of all ages at three level I trauma centers in the United States. They included patients with and without head trauma who had a Glasgow Coma Scale score of 15 and who presented within 4 hours of injury. Investigators screened for concussion symptoms, obtained biomarker data from 712 trauma patients, and conducted repeated blood sampling in adults.
They grouped patients by those with concussion (n = 371), those with head trauma without overt signs of concussion (n = 149), and those with peripheral trauma without head trauma or concussion (n = 192). The study included 175 children. Injury mechanisms included car crashes, falls, bicycle accidents, and sports injuries.
Patients with concussion had significantly higher GFAP concentrations, compared with patients with body trauma and patients with nonconcussive head trauma. UCH-L1 levels did not significantly differ between patients with concussion and head trauma controls, however.
“Based on these results, the potential utility of GFAP to distinguish concussion from body trauma controls over 7 days postinjury was fair to excellent,” with area under the receiver operating characteristics curves (AUCs) of 0.75-0.89, the researchers said. “UCH-L1’s ability was guarded and variable with AUCs from poor to good depending on timing of samples.” UCH-L1 demonstrated AUCs that ranged from 0.54 to 0.78; earlier samples performed better.
GFAP elevations in head trauma controls “may represent milder forms of concussion that do not elicit typical signs or symptoms associated with concussion,” the authors wrote. “These injuries may be irrelevant, or they may represent important trauma that is just below the level of clinical detection and referred to as subconcussive trauma. ... Biomarkers (such as GFAP and UCH-L1) could provide a more objective measure of injury and potentially identify those at risk for neurocognitive problems.”
The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Papa is an unpaid scientific consultant for Banyan Biomarkers, which developed kits to measure the biomarkers, and coauthors receive contract research funding from Banyan Biomarkers.
SOURCE: Papa L et al. BMJ Paediatr Open. 2019 Aug 26. doi: 10.1136/bmjpo-2019-000473.
researchers reported Aug. 26 in BMJ Paediatrics Open.
“GFAP outperformed UCH-L1 in detecting concussion in both children and adults within 4 hours of injury,” reported lead author Linda Papa, MD, and collaborators. Dr. Papa is an emergency medicine doctor at Orlando Health. “UCH-L1 was expressed at much higher levels than GFAP in those with nonconcussive trauma, particularly in children. Elevations of these biomarkers in nonconcussive head trauma suggest possible subconcussive brain injury. GFAP could be potentially useful to detect concussion for up to a week post injury.”
In 2018 the Food and Drug Administration approved the use of these biomarkers to guide CT scan ordering in adults with mild to moderate traumatic brain injury, but investigators have not established their ability to detect concussion in children or adults. Clinicians lack an objective measure to diagnose concussion acutely.
To assess the ability of GFAP and UCH-L1 to detect concussion, Dr. Papa and colleagues conducted a prospective cohort study. The researchers enrolled trauma patients of all ages at three level I trauma centers in the United States. They included patients with and without head trauma who had a Glasgow Coma Scale score of 15 and who presented within 4 hours of injury. Investigators screened for concussion symptoms, obtained biomarker data from 712 trauma patients, and conducted repeated blood sampling in adults.
They grouped patients by those with concussion (n = 371), those with head trauma without overt signs of concussion (n = 149), and those with peripheral trauma without head trauma or concussion (n = 192). The study included 175 children. Injury mechanisms included car crashes, falls, bicycle accidents, and sports injuries.
Patients with concussion had significantly higher GFAP concentrations, compared with patients with body trauma and patients with nonconcussive head trauma. UCH-L1 levels did not significantly differ between patients with concussion and head trauma controls, however.
“Based on these results, the potential utility of GFAP to distinguish concussion from body trauma controls over 7 days postinjury was fair to excellent,” with area under the receiver operating characteristics curves (AUCs) of 0.75-0.89, the researchers said. “UCH-L1’s ability was guarded and variable with AUCs from poor to good depending on timing of samples.” UCH-L1 demonstrated AUCs that ranged from 0.54 to 0.78; earlier samples performed better.
GFAP elevations in head trauma controls “may represent milder forms of concussion that do not elicit typical signs or symptoms associated with concussion,” the authors wrote. “These injuries may be irrelevant, or they may represent important trauma that is just below the level of clinical detection and referred to as subconcussive trauma. ... Biomarkers (such as GFAP and UCH-L1) could provide a more objective measure of injury and potentially identify those at risk for neurocognitive problems.”
The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Papa is an unpaid scientific consultant for Banyan Biomarkers, which developed kits to measure the biomarkers, and coauthors receive contract research funding from Banyan Biomarkers.
SOURCE: Papa L et al. BMJ Paediatr Open. 2019 Aug 26. doi: 10.1136/bmjpo-2019-000473.
FROM BMJ PAEDIATRICS OPEN
Key clinical point: Levels of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) are lowest in patients with nonconcussive body trauma, higher in patients with nonconcussive head trauma, and highest in patients with concussion.
Major finding: GFAP was fair to excellent at distinguishing concussion from body trauma, with area under the receiver operating characteristics curves of 0.75-0.89.
Study details: A prospective cohort study of 712 trauma patients of all ages at three level I trauma centers in the United States. The study included patients with and without head trauma who had a Glasgow Coma Scale score of 15 and presented within 4 hours of injury.
Disclosures: The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Papa is an unpaid scientific consultant for Banyan Biomarkers, which developed kits to measure the biomarkers. Coauthors receive contract research funding from Banyan Biomarkers.
Source: Papa L et al. BMJ Paediatr Open. 2019 Aug 26. doi: 10.1136/bmjpo-2019-000473.
Two genetic variants modify risk of Alzheimer’s disease
according to research published online August 14 in Science Translational Medicine. The variants affect cerebrospinal fluid (CSF) concentrations of a soluble form of the TREM2 protein (sTREM2), which may be involved in Alzheimer’s disease pathology. “Increasing TREM2 or activating the TREM2 signaling pathway could offer a new therapeutic approach for treating Alzheimer’s disease,” wrote the researchers.
Yuetiva Deming, PhD, of the University of Wisconsin–Madison and colleagues conducted a genome-wide association study to identify genetic modifiers of CSF sTREM2. They analyzed CSF sTREM2 levels in 813 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Of this population, 172 participants had Alzheimer’s disease, 169 were cognitively normal, 183 had early mild cognitive impairment (MCI), 221 had late MCI, and 68 had significant memory concerns.
The rs1582763 single-nucleotide polymorphism (SNP) on chromosome 11 within the MS4A gene region was significantly associated with increased CSF levels of sTREM2. Conditional analyses of the MS4A locus indicated that rs6591561, a missense variant within MS4A4A, was associated with reduced CSF sTREM2. Analyzing 580 additional CSF sTREM2 samples, along with associated genetic data, from six other studies replicated these findings in an independent dataset.
Furthermore, Dr. Deming and colleagues found that rs1582763 was associated with reduced risk for Alzheimer’s disease and older age at Alzheimer’s disease onset. In addition, rs6591561 was associated with increased risk of Alzheimer’s disease and earlier onset of Alzheimer’s disease.
Subsequent analyses showed that rs1582763 modified the expression of the MS4A4A and MS4A6A genes in various tissues. This finding suggests that one or both of these genes are important for influencing the production of sTREM2, wrote Dr. Deming and colleagues. Using human macrophages as a proxy for microglia, the investigators observed that the MS4A4A and TREM2 proteins colocalized on lipid rafts at the plasma membrane. In addition, sTREM2 concentrations increased with MS4A4A overexpression, and silencing of MS4A4A reduced sTREM2 production.
These findings “provide a putative biological connection between the MS4A family, TREM2, and Alzheimer’s disease risk,” wrote the researchers. The data also suggest that MS4A4A is a potential therapeutic target in Alzheimer’s disease. Understanding the role of sTREM2 in Alzheimer’s disease will require additional research, but it may be involved in pathogenesis, wrote Dr. Deming and colleagues.
One of the study’s limitations is that the investigators included only common variants and thus could not determine the effect of genes that only harbor low-frequency or rare functional variants. Another limitation is that the data cannot support conclusions about whether other genes in the MS4A locus also modulate sTREM2, wrote Dr. Deming and colleagues.
Grants from the National Institutes of Health supported this study. The investigators disclosed consulting and other relationships with various pharmaceutical companies.
SOURCE: Deming Y et al. Sci Transl Med. 2019 Aug 14. doi: 10.1126/scitranslmed.aau2291.
according to research published online August 14 in Science Translational Medicine. The variants affect cerebrospinal fluid (CSF) concentrations of a soluble form of the TREM2 protein (sTREM2), which may be involved in Alzheimer’s disease pathology. “Increasing TREM2 or activating the TREM2 signaling pathway could offer a new therapeutic approach for treating Alzheimer’s disease,” wrote the researchers.
Yuetiva Deming, PhD, of the University of Wisconsin–Madison and colleagues conducted a genome-wide association study to identify genetic modifiers of CSF sTREM2. They analyzed CSF sTREM2 levels in 813 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Of this population, 172 participants had Alzheimer’s disease, 169 were cognitively normal, 183 had early mild cognitive impairment (MCI), 221 had late MCI, and 68 had significant memory concerns.
The rs1582763 single-nucleotide polymorphism (SNP) on chromosome 11 within the MS4A gene region was significantly associated with increased CSF levels of sTREM2. Conditional analyses of the MS4A locus indicated that rs6591561, a missense variant within MS4A4A, was associated with reduced CSF sTREM2. Analyzing 580 additional CSF sTREM2 samples, along with associated genetic data, from six other studies replicated these findings in an independent dataset.
Furthermore, Dr. Deming and colleagues found that rs1582763 was associated with reduced risk for Alzheimer’s disease and older age at Alzheimer’s disease onset. In addition, rs6591561 was associated with increased risk of Alzheimer’s disease and earlier onset of Alzheimer’s disease.
Subsequent analyses showed that rs1582763 modified the expression of the MS4A4A and MS4A6A genes in various tissues. This finding suggests that one or both of these genes are important for influencing the production of sTREM2, wrote Dr. Deming and colleagues. Using human macrophages as a proxy for microglia, the investigators observed that the MS4A4A and TREM2 proteins colocalized on lipid rafts at the plasma membrane. In addition, sTREM2 concentrations increased with MS4A4A overexpression, and silencing of MS4A4A reduced sTREM2 production.
These findings “provide a putative biological connection between the MS4A family, TREM2, and Alzheimer’s disease risk,” wrote the researchers. The data also suggest that MS4A4A is a potential therapeutic target in Alzheimer’s disease. Understanding the role of sTREM2 in Alzheimer’s disease will require additional research, but it may be involved in pathogenesis, wrote Dr. Deming and colleagues.
One of the study’s limitations is that the investigators included only common variants and thus could not determine the effect of genes that only harbor low-frequency or rare functional variants. Another limitation is that the data cannot support conclusions about whether other genes in the MS4A locus also modulate sTREM2, wrote Dr. Deming and colleagues.
Grants from the National Institutes of Health supported this study. The investigators disclosed consulting and other relationships with various pharmaceutical companies.
SOURCE: Deming Y et al. Sci Transl Med. 2019 Aug 14. doi: 10.1126/scitranslmed.aau2291.
according to research published online August 14 in Science Translational Medicine. The variants affect cerebrospinal fluid (CSF) concentrations of a soluble form of the TREM2 protein (sTREM2), which may be involved in Alzheimer’s disease pathology. “Increasing TREM2 or activating the TREM2 signaling pathway could offer a new therapeutic approach for treating Alzheimer’s disease,” wrote the researchers.
Yuetiva Deming, PhD, of the University of Wisconsin–Madison and colleagues conducted a genome-wide association study to identify genetic modifiers of CSF sTREM2. They analyzed CSF sTREM2 levels in 813 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Of this population, 172 participants had Alzheimer’s disease, 169 were cognitively normal, 183 had early mild cognitive impairment (MCI), 221 had late MCI, and 68 had significant memory concerns.
The rs1582763 single-nucleotide polymorphism (SNP) on chromosome 11 within the MS4A gene region was significantly associated with increased CSF levels of sTREM2. Conditional analyses of the MS4A locus indicated that rs6591561, a missense variant within MS4A4A, was associated with reduced CSF sTREM2. Analyzing 580 additional CSF sTREM2 samples, along with associated genetic data, from six other studies replicated these findings in an independent dataset.
Furthermore, Dr. Deming and colleagues found that rs1582763 was associated with reduced risk for Alzheimer’s disease and older age at Alzheimer’s disease onset. In addition, rs6591561 was associated with increased risk of Alzheimer’s disease and earlier onset of Alzheimer’s disease.
Subsequent analyses showed that rs1582763 modified the expression of the MS4A4A and MS4A6A genes in various tissues. This finding suggests that one or both of these genes are important for influencing the production of sTREM2, wrote Dr. Deming and colleagues. Using human macrophages as a proxy for microglia, the investigators observed that the MS4A4A and TREM2 proteins colocalized on lipid rafts at the plasma membrane. In addition, sTREM2 concentrations increased with MS4A4A overexpression, and silencing of MS4A4A reduced sTREM2 production.
These findings “provide a putative biological connection between the MS4A family, TREM2, and Alzheimer’s disease risk,” wrote the researchers. The data also suggest that MS4A4A is a potential therapeutic target in Alzheimer’s disease. Understanding the role of sTREM2 in Alzheimer’s disease will require additional research, but it may be involved in pathogenesis, wrote Dr. Deming and colleagues.
One of the study’s limitations is that the investigators included only common variants and thus could not determine the effect of genes that only harbor low-frequency or rare functional variants. Another limitation is that the data cannot support conclusions about whether other genes in the MS4A locus also modulate sTREM2, wrote Dr. Deming and colleagues.
Grants from the National Institutes of Health supported this study. The investigators disclosed consulting and other relationships with various pharmaceutical companies.
SOURCE: Deming Y et al. Sci Transl Med. 2019 Aug 14. doi: 10.1126/scitranslmed.aau2291.
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point: Two variants of MS4A are associated with the risk of Alzheimer’s disease.
Major finding: The rs1582763 SNP is associated with reduced risk for Alzheimer’s disease, and rs6591561 is associated with increased risk of Alzheimer’s disease.
Study details: A genome-wide association study of 813 participants in the Alzheimer’s Disease Neuroimaging Initiative.
Disclosures: Grants from the National Institutes of Health supported this study. The investigators disclosed consulting and other relationships with various pharmaceutical companies.
Source: Deming Y et al. Sci Transl Med. 2019 Aug 14. doi: 10.1126/scitranslmed.aau2291.
Serum neurofilament light chain level may indicate MS disease activity
according to an investigation published online August 12 in JAMA Neurology. Furthermore, changes in sNfL levels are associated with disability worsening, and sNfL levels may be influenced by treatment. These data support the potential of sNfL as an objective surrogate of ongoing MS disease activity, according to the researchers.
Neuronal and axonal loss increase levels of NfL in cerebrospinal fluid (CSF) in patients with MS. Previous research indicated that sNfL levels are correlated with CSF levels of NfL and are associated with clinical and imaging measures of disease activity. For the purpose of repeated sampling, collecting blood from patients would be more practical than performing lumbar punctures, said the investigators. No long-term studies of sNfL concentrations and their associations with MS disease outcomes had been performed, however.
Ester Cantó, PhD, of the University of California, San Francisco (UCSF), and colleagues examined data from the prospective Expression, Proteomics, Imaging, Clinical (EPIC) study to assess sNfL as a biomarker of MS disease activity and progression. The ongoing EPIC study is being conducted at UCSF. Dr. Cantó and colleagues analyzed data collected from July 1, 2004, through August 31, 2017, for 607 patients with MS. Participants underwent clinical examinations and serum sample collections annually for 5 years, then at various time points for as long as 12 years. The median follow-up duration was 10 years. The researchers measured sNfL levels with a sensitive single-molecule array platform and compared them with clinical and MRI variables using univariable and multivariable analyses. Dr. Cantó and colleagues chose disability progression, defined as clinically significant worsening on the Expanded Disability Status Scale (EDSS) score, and brain fraction atrophy as their primary outcomes.
The population’s mean age was 42.5 years. About 70% of participants were women, and all were of non-Hispanic European descent. At baseline, sNfL levels were significantly associated with EDSS score, MS subtype, and treatment status.
Dr. Cantó and colleagues found a significant interaction between EDSS worsening and change in levels of sNfL over time. Baseline sNfL levels were associated with approximately 11.6% of the variance in participants’ brain fraction atrophy at year 10. When the investigators controlled for sex, age, and disease duration, they found that baseline sNfL levels were associated with 18% of the variance in brain fraction atrophy at year 10. After 5 years’ follow-up, active treatment was associated with lower levels of sNfL. High-efficacy treatments were associated with greater decreases in sNfL levels, compared with platform therapies.
More frequent sample acquisition could provide greater detail about changes in sNfL levels, wrote Dr. Cantó and colleagues. They acknowledged that their study had insufficient power for the researchers to assess the outcomes of individual MS therapies. Other limitations included the lack of data on NfL stability and the lack of a group of healthy controls.
“For an individual patient, the biomarker prognostic power of sNfL level for clinical and MRI outcomes was limited,” said the investigators. “Further prospective studies are necessary to assess the assay’s utility for decision making in individual patients.”
The National Institutes of Health and the U.S. National MS Society supported the study. Several of the investigators received compensation from Novartis, which provided funds for the reagents needed for the single-molecule array assay.
SOURCE: Cantó E et al. JAMA Neurol. 2019 Aug. 12. doi: 10.1001/jamaneurol.2019.2137.
according to an investigation published online August 12 in JAMA Neurology. Furthermore, changes in sNfL levels are associated with disability worsening, and sNfL levels may be influenced by treatment. These data support the potential of sNfL as an objective surrogate of ongoing MS disease activity, according to the researchers.
Neuronal and axonal loss increase levels of NfL in cerebrospinal fluid (CSF) in patients with MS. Previous research indicated that sNfL levels are correlated with CSF levels of NfL and are associated with clinical and imaging measures of disease activity. For the purpose of repeated sampling, collecting blood from patients would be more practical than performing lumbar punctures, said the investigators. No long-term studies of sNfL concentrations and their associations with MS disease outcomes had been performed, however.
Ester Cantó, PhD, of the University of California, San Francisco (UCSF), and colleagues examined data from the prospective Expression, Proteomics, Imaging, Clinical (EPIC) study to assess sNfL as a biomarker of MS disease activity and progression. The ongoing EPIC study is being conducted at UCSF. Dr. Cantó and colleagues analyzed data collected from July 1, 2004, through August 31, 2017, for 607 patients with MS. Participants underwent clinical examinations and serum sample collections annually for 5 years, then at various time points for as long as 12 years. The median follow-up duration was 10 years. The researchers measured sNfL levels with a sensitive single-molecule array platform and compared them with clinical and MRI variables using univariable and multivariable analyses. Dr. Cantó and colleagues chose disability progression, defined as clinically significant worsening on the Expanded Disability Status Scale (EDSS) score, and brain fraction atrophy as their primary outcomes.
The population’s mean age was 42.5 years. About 70% of participants were women, and all were of non-Hispanic European descent. At baseline, sNfL levels were significantly associated with EDSS score, MS subtype, and treatment status.
Dr. Cantó and colleagues found a significant interaction between EDSS worsening and change in levels of sNfL over time. Baseline sNfL levels were associated with approximately 11.6% of the variance in participants’ brain fraction atrophy at year 10. When the investigators controlled for sex, age, and disease duration, they found that baseline sNfL levels were associated with 18% of the variance in brain fraction atrophy at year 10. After 5 years’ follow-up, active treatment was associated with lower levels of sNfL. High-efficacy treatments were associated with greater decreases in sNfL levels, compared with platform therapies.
More frequent sample acquisition could provide greater detail about changes in sNfL levels, wrote Dr. Cantó and colleagues. They acknowledged that their study had insufficient power for the researchers to assess the outcomes of individual MS therapies. Other limitations included the lack of data on NfL stability and the lack of a group of healthy controls.
“For an individual patient, the biomarker prognostic power of sNfL level for clinical and MRI outcomes was limited,” said the investigators. “Further prospective studies are necessary to assess the assay’s utility for decision making in individual patients.”
The National Institutes of Health and the U.S. National MS Society supported the study. Several of the investigators received compensation from Novartis, which provided funds for the reagents needed for the single-molecule array assay.
SOURCE: Cantó E et al. JAMA Neurol. 2019 Aug. 12. doi: 10.1001/jamaneurol.2019.2137.
according to an investigation published online August 12 in JAMA Neurology. Furthermore, changes in sNfL levels are associated with disability worsening, and sNfL levels may be influenced by treatment. These data support the potential of sNfL as an objective surrogate of ongoing MS disease activity, according to the researchers.
Neuronal and axonal loss increase levels of NfL in cerebrospinal fluid (CSF) in patients with MS. Previous research indicated that sNfL levels are correlated with CSF levels of NfL and are associated with clinical and imaging measures of disease activity. For the purpose of repeated sampling, collecting blood from patients would be more practical than performing lumbar punctures, said the investigators. No long-term studies of sNfL concentrations and their associations with MS disease outcomes had been performed, however.
Ester Cantó, PhD, of the University of California, San Francisco (UCSF), and colleagues examined data from the prospective Expression, Proteomics, Imaging, Clinical (EPIC) study to assess sNfL as a biomarker of MS disease activity and progression. The ongoing EPIC study is being conducted at UCSF. Dr. Cantó and colleagues analyzed data collected from July 1, 2004, through August 31, 2017, for 607 patients with MS. Participants underwent clinical examinations and serum sample collections annually for 5 years, then at various time points for as long as 12 years. The median follow-up duration was 10 years. The researchers measured sNfL levels with a sensitive single-molecule array platform and compared them with clinical and MRI variables using univariable and multivariable analyses. Dr. Cantó and colleagues chose disability progression, defined as clinically significant worsening on the Expanded Disability Status Scale (EDSS) score, and brain fraction atrophy as their primary outcomes.
The population’s mean age was 42.5 years. About 70% of participants were women, and all were of non-Hispanic European descent. At baseline, sNfL levels were significantly associated with EDSS score, MS subtype, and treatment status.
Dr. Cantó and colleagues found a significant interaction between EDSS worsening and change in levels of sNfL over time. Baseline sNfL levels were associated with approximately 11.6% of the variance in participants’ brain fraction atrophy at year 10. When the investigators controlled for sex, age, and disease duration, they found that baseline sNfL levels were associated with 18% of the variance in brain fraction atrophy at year 10. After 5 years’ follow-up, active treatment was associated with lower levels of sNfL. High-efficacy treatments were associated with greater decreases in sNfL levels, compared with platform therapies.
More frequent sample acquisition could provide greater detail about changes in sNfL levels, wrote Dr. Cantó and colleagues. They acknowledged that their study had insufficient power for the researchers to assess the outcomes of individual MS therapies. Other limitations included the lack of data on NfL stability and the lack of a group of healthy controls.
“For an individual patient, the biomarker prognostic power of sNfL level for clinical and MRI outcomes was limited,” said the investigators. “Further prospective studies are necessary to assess the assay’s utility for decision making in individual patients.”
The National Institutes of Health and the U.S. National MS Society supported the study. Several of the investigators received compensation from Novartis, which provided funds for the reagents needed for the single-molecule array assay.
SOURCE: Cantó E et al. JAMA Neurol. 2019 Aug. 12. doi: 10.1001/jamaneurol.2019.2137.
FROM JAMA NEUROLOGY
Key clinical point: Serum neurofilament light chain level has potential as a surrogate of ongoing MS disease activity.
Major finding: Serum neurofilament light chain level is associated with brain fraction atrophy.
Study details: An ongoing, prospective, observational study of 607 patients with MS.
Disclosures: The National Institutes of Health and the U.S. National MS Society supported the study. Several of the investigators received compensation from Novartis, which provided funds for the reagents needed for the single-molecule array assay.
Source: Cantó E et al. JAMA Neurol. 2019 Aug 12. doi: 10.1001/jamaneurol.2019.2137.
Vaccination is not associated with increased risk of MS
(MS), according to an analysis published July 30 in Neurology. Although the results suggest that vaccination is associated with a lower likelihood of incident MS within the following 5 years, “these data alone do not allow for any conclusion regarding a possible protective effect of vaccinations regarding the development of MS,” wrote Alexander Hapfelmeier, PhD, of the Technical University of Munich and colleagues.
In recent years, researchers have proposed and investigated various potential environmental risk factors for the development of MS. Vaccination is one proposed environmental risk factor, but case reports and small studies have yielded conflicting results about its association with incident MS.
To examine this question more closely, Dr. Hapfelmeier and colleagues performed a systematic retrospective analysis of ambulatory claims data held by the Bavarian Association of Statutory Health Insurance Physicians. They reviewed the data to identify patients with new-onset MS and at least two ICD-10 diagnoses of the disorder. They next identified two control cohorts of participants diagnosed with other autoimmune diseases: Crohn’s disease and psoriasis. Finally, they randomly selected a third control cohort of patients without any of these diagnoses and matched them by age, sex, and district to patients with MS in a 5:1 ratio. Eligible participants were younger than 70 years.
Dr. Hapfelmeier and colleagues reviewed the incidence and frequency of vaccinations (such as those targeting tick-borne encephalitis, human papillomavirus, and influenza virus) in all cohorts. They created unconditional logistic regression models to assess the association between vaccination and MS. They also created separate models to contrast the MS cohort with each of the control cohorts.
The researchers included 12,262 patients with MS, 19,296 patients with Crohn’s disease, 112,292 patients with psoriasis, and 79,185 participants without these autoimmune diseases in their analysis. They found 456 participants with Crohn’s disease and psoriasis, 216 participants with MS and psoriasis, 48 participants with Crohn’s disease and MS, and 2 participants with Crohn’s disease, psoriasis, and MS. Dr. Hapfelmeier and colleagues allocated these participants to each of the respective cohorts and did not analyze them differently because of the comparatively small sample sizes.
The investigators analyzed the occurrence of vaccination in all participants during the 5 years before first diagnosis. Among patients who received vaccination, the odds ratio of MS was 0.870 in participants without autoimmune disease, 0.919 in participants with Crohn’s disease, and 0.973 in participants with psoriasis. Decreased risk of MS was most notable for vaccinations against influenza and tick-borne encephalitis. The results were consistent regardless of time frame, control cohort, and definition of MS.
The subjective definition of the MS cohort was a limitation of the study, but the authors addressed it by also using several strict definitions of that cohort. Another limitation is that the source data may reflect entry errors and incorrect coding.
A grant from the German Federal Ministry of Education and Research Competence Network MS supported the study. The authors had no conflicts that were relevant to the topic of the study.
SOURCE: Hapfelmeier A et al. Neurology. 2019 Jul 30. doi: 10.1212/WNL.0000000000008012.
The analysis by Hapfelmeier et al. provides important evidence that vaccinations are not associated with multiple sclerosis (MS), said E. Ann Yeh, MD, a neurologist at the Hospital for Sick Children in Toronto, and Jennifer Graves, MD, PhD, a neurologist at the University of California, San Diego, in an accompanying editorial. On the contrary, the evidence supports a potential protective effect of vaccines on the risk of developing MS, they said.
“The reasons for this [finding] cannot be gleaned from this study and may range from biological to sociocultural/demographic reasons,” the authors added. “Infection, rather than vaccination, may be an MS trigger, or individuals obtaining vaccinations may be practicing other healthy behaviors protective for MS. These possibilities should be the subject of future studies.”
Until future studies are completed and their results published, the findings of Hapfelmeier et al. offer “strong evidence to share with worried patients and families when faced with the question of whether a vaccine in the recent or relatively distant past triggered the individual’s MS,” said Dr. Yeh and Dr. Graves.
The authors had various relationships with industry, including serving on advisory boards for and receiving funding from pharmaceutical companies.
The analysis by Hapfelmeier et al. provides important evidence that vaccinations are not associated with multiple sclerosis (MS), said E. Ann Yeh, MD, a neurologist at the Hospital for Sick Children in Toronto, and Jennifer Graves, MD, PhD, a neurologist at the University of California, San Diego, in an accompanying editorial. On the contrary, the evidence supports a potential protective effect of vaccines on the risk of developing MS, they said.
“The reasons for this [finding] cannot be gleaned from this study and may range from biological to sociocultural/demographic reasons,” the authors added. “Infection, rather than vaccination, may be an MS trigger, or individuals obtaining vaccinations may be practicing other healthy behaviors protective for MS. These possibilities should be the subject of future studies.”
Until future studies are completed and their results published, the findings of Hapfelmeier et al. offer “strong evidence to share with worried patients and families when faced with the question of whether a vaccine in the recent or relatively distant past triggered the individual’s MS,” said Dr. Yeh and Dr. Graves.
The authors had various relationships with industry, including serving on advisory boards for and receiving funding from pharmaceutical companies.
The analysis by Hapfelmeier et al. provides important evidence that vaccinations are not associated with multiple sclerosis (MS), said E. Ann Yeh, MD, a neurologist at the Hospital for Sick Children in Toronto, and Jennifer Graves, MD, PhD, a neurologist at the University of California, San Diego, in an accompanying editorial. On the contrary, the evidence supports a potential protective effect of vaccines on the risk of developing MS, they said.
“The reasons for this [finding] cannot be gleaned from this study and may range from biological to sociocultural/demographic reasons,” the authors added. “Infection, rather than vaccination, may be an MS trigger, or individuals obtaining vaccinations may be practicing other healthy behaviors protective for MS. These possibilities should be the subject of future studies.”
Until future studies are completed and their results published, the findings of Hapfelmeier et al. offer “strong evidence to share with worried patients and families when faced with the question of whether a vaccine in the recent or relatively distant past triggered the individual’s MS,” said Dr. Yeh and Dr. Graves.
The authors had various relationships with industry, including serving on advisory boards for and receiving funding from pharmaceutical companies.
(MS), according to an analysis published July 30 in Neurology. Although the results suggest that vaccination is associated with a lower likelihood of incident MS within the following 5 years, “these data alone do not allow for any conclusion regarding a possible protective effect of vaccinations regarding the development of MS,” wrote Alexander Hapfelmeier, PhD, of the Technical University of Munich and colleagues.
In recent years, researchers have proposed and investigated various potential environmental risk factors for the development of MS. Vaccination is one proposed environmental risk factor, but case reports and small studies have yielded conflicting results about its association with incident MS.
To examine this question more closely, Dr. Hapfelmeier and colleagues performed a systematic retrospective analysis of ambulatory claims data held by the Bavarian Association of Statutory Health Insurance Physicians. They reviewed the data to identify patients with new-onset MS and at least two ICD-10 diagnoses of the disorder. They next identified two control cohorts of participants diagnosed with other autoimmune diseases: Crohn’s disease and psoriasis. Finally, they randomly selected a third control cohort of patients without any of these diagnoses and matched them by age, sex, and district to patients with MS in a 5:1 ratio. Eligible participants were younger than 70 years.
Dr. Hapfelmeier and colleagues reviewed the incidence and frequency of vaccinations (such as those targeting tick-borne encephalitis, human papillomavirus, and influenza virus) in all cohorts. They created unconditional logistic regression models to assess the association between vaccination and MS. They also created separate models to contrast the MS cohort with each of the control cohorts.
The researchers included 12,262 patients with MS, 19,296 patients with Crohn’s disease, 112,292 patients with psoriasis, and 79,185 participants without these autoimmune diseases in their analysis. They found 456 participants with Crohn’s disease and psoriasis, 216 participants with MS and psoriasis, 48 participants with Crohn’s disease and MS, and 2 participants with Crohn’s disease, psoriasis, and MS. Dr. Hapfelmeier and colleagues allocated these participants to each of the respective cohorts and did not analyze them differently because of the comparatively small sample sizes.
The investigators analyzed the occurrence of vaccination in all participants during the 5 years before first diagnosis. Among patients who received vaccination, the odds ratio of MS was 0.870 in participants without autoimmune disease, 0.919 in participants with Crohn’s disease, and 0.973 in participants with psoriasis. Decreased risk of MS was most notable for vaccinations against influenza and tick-borne encephalitis. The results were consistent regardless of time frame, control cohort, and definition of MS.
The subjective definition of the MS cohort was a limitation of the study, but the authors addressed it by also using several strict definitions of that cohort. Another limitation is that the source data may reflect entry errors and incorrect coding.
A grant from the German Federal Ministry of Education and Research Competence Network MS supported the study. The authors had no conflicts that were relevant to the topic of the study.
SOURCE: Hapfelmeier A et al. Neurology. 2019 Jul 30. doi: 10.1212/WNL.0000000000008012.
(MS), according to an analysis published July 30 in Neurology. Although the results suggest that vaccination is associated with a lower likelihood of incident MS within the following 5 years, “these data alone do not allow for any conclusion regarding a possible protective effect of vaccinations regarding the development of MS,” wrote Alexander Hapfelmeier, PhD, of the Technical University of Munich and colleagues.
In recent years, researchers have proposed and investigated various potential environmental risk factors for the development of MS. Vaccination is one proposed environmental risk factor, but case reports and small studies have yielded conflicting results about its association with incident MS.
To examine this question more closely, Dr. Hapfelmeier and colleagues performed a systematic retrospective analysis of ambulatory claims data held by the Bavarian Association of Statutory Health Insurance Physicians. They reviewed the data to identify patients with new-onset MS and at least two ICD-10 diagnoses of the disorder. They next identified two control cohorts of participants diagnosed with other autoimmune diseases: Crohn’s disease and psoriasis. Finally, they randomly selected a third control cohort of patients without any of these diagnoses and matched them by age, sex, and district to patients with MS in a 5:1 ratio. Eligible participants were younger than 70 years.
Dr. Hapfelmeier and colleagues reviewed the incidence and frequency of vaccinations (such as those targeting tick-borne encephalitis, human papillomavirus, and influenza virus) in all cohorts. They created unconditional logistic regression models to assess the association between vaccination and MS. They also created separate models to contrast the MS cohort with each of the control cohorts.
The researchers included 12,262 patients with MS, 19,296 patients with Crohn’s disease, 112,292 patients with psoriasis, and 79,185 participants without these autoimmune diseases in their analysis. They found 456 participants with Crohn’s disease and psoriasis, 216 participants with MS and psoriasis, 48 participants with Crohn’s disease and MS, and 2 participants with Crohn’s disease, psoriasis, and MS. Dr. Hapfelmeier and colleagues allocated these participants to each of the respective cohorts and did not analyze them differently because of the comparatively small sample sizes.
The investigators analyzed the occurrence of vaccination in all participants during the 5 years before first diagnosis. Among patients who received vaccination, the odds ratio of MS was 0.870 in participants without autoimmune disease, 0.919 in participants with Crohn’s disease, and 0.973 in participants with psoriasis. Decreased risk of MS was most notable for vaccinations against influenza and tick-borne encephalitis. The results were consistent regardless of time frame, control cohort, and definition of MS.
The subjective definition of the MS cohort was a limitation of the study, but the authors addressed it by also using several strict definitions of that cohort. Another limitation is that the source data may reflect entry errors and incorrect coding.
A grant from the German Federal Ministry of Education and Research Competence Network MS supported the study. The authors had no conflicts that were relevant to the topic of the study.
SOURCE: Hapfelmeier A et al. Neurology. 2019 Jul 30. doi: 10.1212/WNL.0000000000008012.
FROM NEUROLOGY
Hemoglobin levels are associated with long-term dementia risk
This U-shaped association “may relate to differences in white matter integrity and cerebral perfusion,” the researchers wrote in Neurology.
“With around 10% of people over age 65 having anemia in the Americas and Europe and up to 45% in African and southeast Asian countries, these results could have important implications for the burden of dementia,” said study author M. Arfan Ikram, MD, PhD, in a news release. Dr. Ikram is a professor of epidemiology at Erasmus Medical Center in Rotterdam, the Netherlands.
Prior studies have found that low hemoglobin levels are associated with adverse health outcomes, such as coronary heart disease, stroke, and mortality, but data about the relationship between hemoglobin levels and dementia risk have been limited.
A population-based cohort study
To examine the long-term association of hemoglobin levels and anemia with risk of dementia, Dr. Ikram and coauthors analyzed data from the Rotterdam Study, an ongoing population-based cohort study in the Netherlands that started in 1990. Their analysis included data from 12,305 participants without dementia who had serum hemoglobin measured at baseline (mean age, 64.6 years; 57.7% women).
During a mean follow-up of 12.1 years, 1,520 participants developed dementia, 1,194 of whom had Alzheimer’s disease.
“Both low and high hemoglobin levels were associated with increased dementia risk,” the authors wrote. Compared with participants in the middle quintile of hemoglobin levels (8.57-8.99 mmol/L), participants in the lowest quintile (less than 8.11 mmol/L) had a hazard ratio of dementia of 1.29, and participants in the highest quintile (greater than 9.40 mmol/L) had an HR of 1.20.
About 6% of the participants had anemia – that is, a hemoglobin level of less than 8.1 mmol/L for men and less than 7.5 mmol/L for women. Anemia was associated with a 34% increased risk of dementia and a 41% increased risk of Alzheimer’s disease.
Of the 745 people with anemia, 128 developed dementia, compared with 1,392 of the 11,560 people who did not have anemia (17% vs. 12%).
A U-shaped association
The researchers also examined hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion among 5,267 participants without dementia who had brain MRI. White matter hyperintensity volume and hemoglobin had a U-shaped association, similar to that for dementia and hemoglobin. In addition, hemoglobin inversely correlated to cerebral perfusion.
The results remained consistent after adjustment for factors such as smoking, high blood pressure, high cholesterol, and alcohol use.
A limitation of the study is that the participants lived in the Netherlands and were primarily of European descent, so the results may not apply to other populations, the authors wrote.
Dr. Ikram noted that the study does not prove that low or high hemoglobin levels cause dementia. “More research is needed to determine whether hemoglobin levels play a direct role in this increased risk or whether these associations can be explained by underlying issues or other vascular or metabolic changes.”
The study was supported by the Netherlands Cardiovascular Research Initiative; Erasmus Medical Centre; Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomic Initiative; Dutch Ministry of Education, Culture, and Science; Dutch Ministry of Health, Welfare, and Sports; European Commission; Municipality of Rotterdam; Netherlands Consortium for Healthy Aging; and Dutch Heart Foundation. The authors reported no relevant disclosures.
SOURCE: Ikram MA et al. Neurology. 2019 Jul 31. doi: 10.1212/WNL.0000000000008003.
This U-shaped association “may relate to differences in white matter integrity and cerebral perfusion,” the researchers wrote in Neurology.
“With around 10% of people over age 65 having anemia in the Americas and Europe and up to 45% in African and southeast Asian countries, these results could have important implications for the burden of dementia,” said study author M. Arfan Ikram, MD, PhD, in a news release. Dr. Ikram is a professor of epidemiology at Erasmus Medical Center in Rotterdam, the Netherlands.
Prior studies have found that low hemoglobin levels are associated with adverse health outcomes, such as coronary heart disease, stroke, and mortality, but data about the relationship between hemoglobin levels and dementia risk have been limited.
A population-based cohort study
To examine the long-term association of hemoglobin levels and anemia with risk of dementia, Dr. Ikram and coauthors analyzed data from the Rotterdam Study, an ongoing population-based cohort study in the Netherlands that started in 1990. Their analysis included data from 12,305 participants without dementia who had serum hemoglobin measured at baseline (mean age, 64.6 years; 57.7% women).
During a mean follow-up of 12.1 years, 1,520 participants developed dementia, 1,194 of whom had Alzheimer’s disease.
“Both low and high hemoglobin levels were associated with increased dementia risk,” the authors wrote. Compared with participants in the middle quintile of hemoglobin levels (8.57-8.99 mmol/L), participants in the lowest quintile (less than 8.11 mmol/L) had a hazard ratio of dementia of 1.29, and participants in the highest quintile (greater than 9.40 mmol/L) had an HR of 1.20.
About 6% of the participants had anemia – that is, a hemoglobin level of less than 8.1 mmol/L for men and less than 7.5 mmol/L for women. Anemia was associated with a 34% increased risk of dementia and a 41% increased risk of Alzheimer’s disease.
Of the 745 people with anemia, 128 developed dementia, compared with 1,392 of the 11,560 people who did not have anemia (17% vs. 12%).
A U-shaped association
The researchers also examined hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion among 5,267 participants without dementia who had brain MRI. White matter hyperintensity volume and hemoglobin had a U-shaped association, similar to that for dementia and hemoglobin. In addition, hemoglobin inversely correlated to cerebral perfusion.
The results remained consistent after adjustment for factors such as smoking, high blood pressure, high cholesterol, and alcohol use.
A limitation of the study is that the participants lived in the Netherlands and were primarily of European descent, so the results may not apply to other populations, the authors wrote.
Dr. Ikram noted that the study does not prove that low or high hemoglobin levels cause dementia. “More research is needed to determine whether hemoglobin levels play a direct role in this increased risk or whether these associations can be explained by underlying issues or other vascular or metabolic changes.”
The study was supported by the Netherlands Cardiovascular Research Initiative; Erasmus Medical Centre; Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomic Initiative; Dutch Ministry of Education, Culture, and Science; Dutch Ministry of Health, Welfare, and Sports; European Commission; Municipality of Rotterdam; Netherlands Consortium for Healthy Aging; and Dutch Heart Foundation. The authors reported no relevant disclosures.
SOURCE: Ikram MA et al. Neurology. 2019 Jul 31. doi: 10.1212/WNL.0000000000008003.
This U-shaped association “may relate to differences in white matter integrity and cerebral perfusion,” the researchers wrote in Neurology.
“With around 10% of people over age 65 having anemia in the Americas and Europe and up to 45% in African and southeast Asian countries, these results could have important implications for the burden of dementia,” said study author M. Arfan Ikram, MD, PhD, in a news release. Dr. Ikram is a professor of epidemiology at Erasmus Medical Center in Rotterdam, the Netherlands.
Prior studies have found that low hemoglobin levels are associated with adverse health outcomes, such as coronary heart disease, stroke, and mortality, but data about the relationship between hemoglobin levels and dementia risk have been limited.
A population-based cohort study
To examine the long-term association of hemoglobin levels and anemia with risk of dementia, Dr. Ikram and coauthors analyzed data from the Rotterdam Study, an ongoing population-based cohort study in the Netherlands that started in 1990. Their analysis included data from 12,305 participants without dementia who had serum hemoglobin measured at baseline (mean age, 64.6 years; 57.7% women).
During a mean follow-up of 12.1 years, 1,520 participants developed dementia, 1,194 of whom had Alzheimer’s disease.
“Both low and high hemoglobin levels were associated with increased dementia risk,” the authors wrote. Compared with participants in the middle quintile of hemoglobin levels (8.57-8.99 mmol/L), participants in the lowest quintile (less than 8.11 mmol/L) had a hazard ratio of dementia of 1.29, and participants in the highest quintile (greater than 9.40 mmol/L) had an HR of 1.20.
About 6% of the participants had anemia – that is, a hemoglobin level of less than 8.1 mmol/L for men and less than 7.5 mmol/L for women. Anemia was associated with a 34% increased risk of dementia and a 41% increased risk of Alzheimer’s disease.
Of the 745 people with anemia, 128 developed dementia, compared with 1,392 of the 11,560 people who did not have anemia (17% vs. 12%).
A U-shaped association
The researchers also examined hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion among 5,267 participants without dementia who had brain MRI. White matter hyperintensity volume and hemoglobin had a U-shaped association, similar to that for dementia and hemoglobin. In addition, hemoglobin inversely correlated to cerebral perfusion.
The results remained consistent after adjustment for factors such as smoking, high blood pressure, high cholesterol, and alcohol use.
A limitation of the study is that the participants lived in the Netherlands and were primarily of European descent, so the results may not apply to other populations, the authors wrote.
Dr. Ikram noted that the study does not prove that low or high hemoglobin levels cause dementia. “More research is needed to determine whether hemoglobin levels play a direct role in this increased risk or whether these associations can be explained by underlying issues or other vascular or metabolic changes.”
The study was supported by the Netherlands Cardiovascular Research Initiative; Erasmus Medical Centre; Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomic Initiative; Dutch Ministry of Education, Culture, and Science; Dutch Ministry of Health, Welfare, and Sports; European Commission; Municipality of Rotterdam; Netherlands Consortium for Healthy Aging; and Dutch Heart Foundation. The authors reported no relevant disclosures.
SOURCE: Ikram MA et al. Neurology. 2019 Jul 31. doi: 10.1212/WNL.0000000000008003.
FROM NEUROLOGY
Key clinical point: Adults with low levels of hemoglobin and adults with high levels of hemoglobin may have an increased risk of dementia.
Major finding: Compared with participants in the middle quintile of hemoglobin levels (8.57-8.99 mmol/L), participants in the lowest quintile (less than 8.11 mmol/L) had a hazard ratio of dementia of 1.29, and participants in the highest quintile (greater than 9.40 mmol/L) had an HR of 1.20.
Study details: An analysis of data from 12,305 participants in the Rotterdam Study, a population-based cohort study in the Netherlands, who were followed up for an average of 12 years.
Disclosures: The study was supported by the Netherlands Cardiovascular Research Initiative; Erasmus Medical Centre; Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomic Initiative; Dutch Ministry of Education, Culture, and Science; Dutch Ministry of Health, Welfare, and Sports; European Commission; Municipality of Rotterdam; Netherlands Consortium for Healthy Aging; and Dutch Heart Foundation. The authors reported no relevant disclosures.
Source: Ikram MA et al. Neurology. 2019 Jul 31. doi: 10.1212/WNL.0000000000008003.
Obesity tied to relapse in young patients with multiple sclerosis
, results of a recent large, single-center study show. The rate of switching to second-line disease-modifying therapy was consequently about 50% higher among the obese children in the study, which included a total of 453 pediatric patients.
The link between obesity and treatment response suggests that the management of these younger patients with MS could be improved through weight loss or body mass index (BMI)-adjusted dosing, according to Peter Huppke, MD, of Georg August University in Göttingen, Germany, and co-investigators.
“The findings do not indicate that obesity promotes greater disease activity, but pharmacokinetic factors are more likely associated with treatment response,” Dr. Huppke and co-authors said in a report on their study, which was published online ahead of print July 15 in JAMA Neurology.
This is believed to be the first-ever study to find an association between BMI and treatment response in pediatric patients with MS, according to the authors, who said they also confirmed a link between obesity and MS.
Specifically, obesity increased MS susceptibility by two-fold as compared with healthy controls, a finding that they said adds to a small but growing body of evidence that high BMI is associated with increased risk of the disease in these younger individuals.
This retrospective study included 453 pediatric patients with MS treated at the Center for MS in Childhood and Adolescence in Göttingen, Germany between 1990 and 2016. About two-thirds were female and the mean age at MS diagnosis was about 14 years.
Of those patients, 126 (27.8%) were classified as obese based on a BMI greater than the 90th percentile, according to the report.
Dr. Huppke and co-investigators found that high BMI was linked to a significantly increased odds of pediatric MS, with odds ratios of 2.19 (95% CI, 1.5-3.1; P < 0.001) in girls and 2.14 (95% CI, 1.3-3.5; P = 0.003) in boys.
A total of 277 of these pediatric patients received a first-line disease-modifying therapy for 6 months or longer, including 249 treated with interferon beta and 51 treated with glatiramer.
Relapses were more common in obese patients, according to the report. with an annualized relapse rate of 1.29, compared to just 0.72 for those who were not overweight (P < 0.001).
Consequently, likelihood of receiving a second-line treatment was about 1.5 times higher in the obese or extremely obese patients, investigators said.
“A healthy weight may potentially optimize treatment outcomes and reduce disease-related burden and health care costs,” they concluded in the report, adding that BMI-adjusted dosing may “increase the value” of first-line disease-modifying therapies.
Dr. Huppke reported disclosures related to Bayer Health Care, Merck Serono, and Novartis not associated with the current study.
SOURCE: Huppke B, et al. JAMA Neurol. 2019 Jul 15. doi: 10.1001/jamaneurol.2019.1997
, results of a recent large, single-center study show. The rate of switching to second-line disease-modifying therapy was consequently about 50% higher among the obese children in the study, which included a total of 453 pediatric patients.
The link between obesity and treatment response suggests that the management of these younger patients with MS could be improved through weight loss or body mass index (BMI)-adjusted dosing, according to Peter Huppke, MD, of Georg August University in Göttingen, Germany, and co-investigators.
“The findings do not indicate that obesity promotes greater disease activity, but pharmacokinetic factors are more likely associated with treatment response,” Dr. Huppke and co-authors said in a report on their study, which was published online ahead of print July 15 in JAMA Neurology.
This is believed to be the first-ever study to find an association between BMI and treatment response in pediatric patients with MS, according to the authors, who said they also confirmed a link between obesity and MS.
Specifically, obesity increased MS susceptibility by two-fold as compared with healthy controls, a finding that they said adds to a small but growing body of evidence that high BMI is associated with increased risk of the disease in these younger individuals.
This retrospective study included 453 pediatric patients with MS treated at the Center for MS in Childhood and Adolescence in Göttingen, Germany between 1990 and 2016. About two-thirds were female and the mean age at MS diagnosis was about 14 years.
Of those patients, 126 (27.8%) were classified as obese based on a BMI greater than the 90th percentile, according to the report.
Dr. Huppke and co-investigators found that high BMI was linked to a significantly increased odds of pediatric MS, with odds ratios of 2.19 (95% CI, 1.5-3.1; P < 0.001) in girls and 2.14 (95% CI, 1.3-3.5; P = 0.003) in boys.
A total of 277 of these pediatric patients received a first-line disease-modifying therapy for 6 months or longer, including 249 treated with interferon beta and 51 treated with glatiramer.
Relapses were more common in obese patients, according to the report. with an annualized relapse rate of 1.29, compared to just 0.72 for those who were not overweight (P < 0.001).
Consequently, likelihood of receiving a second-line treatment was about 1.5 times higher in the obese or extremely obese patients, investigators said.
“A healthy weight may potentially optimize treatment outcomes and reduce disease-related burden and health care costs,” they concluded in the report, adding that BMI-adjusted dosing may “increase the value” of first-line disease-modifying therapies.
Dr. Huppke reported disclosures related to Bayer Health Care, Merck Serono, and Novartis not associated with the current study.
SOURCE: Huppke B, et al. JAMA Neurol. 2019 Jul 15. doi: 10.1001/jamaneurol.2019.1997
, results of a recent large, single-center study show. The rate of switching to second-line disease-modifying therapy was consequently about 50% higher among the obese children in the study, which included a total of 453 pediatric patients.
The link between obesity and treatment response suggests that the management of these younger patients with MS could be improved through weight loss or body mass index (BMI)-adjusted dosing, according to Peter Huppke, MD, of Georg August University in Göttingen, Germany, and co-investigators.
“The findings do not indicate that obesity promotes greater disease activity, but pharmacokinetic factors are more likely associated with treatment response,” Dr. Huppke and co-authors said in a report on their study, which was published online ahead of print July 15 in JAMA Neurology.
This is believed to be the first-ever study to find an association between BMI and treatment response in pediatric patients with MS, according to the authors, who said they also confirmed a link between obesity and MS.
Specifically, obesity increased MS susceptibility by two-fold as compared with healthy controls, a finding that they said adds to a small but growing body of evidence that high BMI is associated with increased risk of the disease in these younger individuals.
This retrospective study included 453 pediatric patients with MS treated at the Center for MS in Childhood and Adolescence in Göttingen, Germany between 1990 and 2016. About two-thirds were female and the mean age at MS diagnosis was about 14 years.
Of those patients, 126 (27.8%) were classified as obese based on a BMI greater than the 90th percentile, according to the report.
Dr. Huppke and co-investigators found that high BMI was linked to a significantly increased odds of pediatric MS, with odds ratios of 2.19 (95% CI, 1.5-3.1; P < 0.001) in girls and 2.14 (95% CI, 1.3-3.5; P = 0.003) in boys.
A total of 277 of these pediatric patients received a first-line disease-modifying therapy for 6 months or longer, including 249 treated with interferon beta and 51 treated with glatiramer.
Relapses were more common in obese patients, according to the report. with an annualized relapse rate of 1.29, compared to just 0.72 for those who were not overweight (P < 0.001).
Consequently, likelihood of receiving a second-line treatment was about 1.5 times higher in the obese or extremely obese patients, investigators said.
“A healthy weight may potentially optimize treatment outcomes and reduce disease-related burden and health care costs,” they concluded in the report, adding that BMI-adjusted dosing may “increase the value” of first-line disease-modifying therapies.
Dr. Huppke reported disclosures related to Bayer Health Care, Merck Serono, and Novartis not associated with the current study.
SOURCE: Huppke B, et al. JAMA Neurol. 2019 Jul 15. doi: 10.1001/jamaneurol.2019.1997
FROM JAMA NEUROLOGY
Key clinical point: Obese children and adolescents with MS had about twice as many relapses on first-line treatment as compared with their non-obese counterparts.
Major finding: The annualized relapse rate was 1.29 for obese pediatric patients, compared to 0.72 for those who were not overweight (P < 0.001).
Study details: Retrospective study including 453 patients with pediatric MS treated at a center in Göttingen, Germany between 1990 and 2016.
Disclosures: The senior author reported disclosures related to Bayer Health Care, Merck Serono, and Novartis unrelated to the this study.
Source: Huppke B, et al. JAMA Neurol. 2019 Jul 15.
Nerve transfer improves function after spinal cord injury
according to research published online July 4 ahead of print in the Lancet. Combining nerve transfer with tendon transfer may maximize the functional benefit of surgery.
The loss of upper extremity function after cervical spinal cord injury can reduce independence and social and vocational engagement. People with tetraplegia rank improvement in hand function as their most important goal. Tendon transfers have been the traditional method of restoring function, but interest in nerve transfers has been increasing with the publication of successful results. Nerve transfers can reanimate several muscles at once and require a smaller incision and shorter immobilization, compared with tendon transfers.
Injury had occurred less than 18 months previously
Natasha van Zyl, MBBS, a plastic and reconstructive surgeon at Austin Health in Melbourne, and colleagues conducted a prospective case series to examine the clinical and functional outcomes of nerve transfer surgery for the reanimation of upper limb function in patients with tetraplegia. The investigators also sought to compare these outcomes with published outcomes for tendon transfer surgery.
Between April 14, 2014, and Nov. 22, 2018, Dr. van Zyl and colleagues recruited consecutive patients of any age with early cervical spinal cord injury of motor level C5 and below. Injury was required to have occurred fewer than 18 months before enrollment. Eligible participants had been referred to a single center for upper extremity reanimation and were considered candidates for nerve transfer.
Every participant underwent single or multiple nerve transfers in one or both upper limbs, and some participants also underwent tendon transfers. The goal of surgery was the restoration of elbow extension, grasp, pinch, and hand opening. An independent assessor evaluated participants at baseline and at 12 months and 24 months after surgery. The primary outcome measures were the action research arm test (ARAT), the grasp release test (GRT), and the spinal cord independence measure (SCIM).
Grasp function improved significantly
Dr. van Zyl and colleagues recruited 16 participants with traumatic spinal cord injury who underwent 59 nerve transfers. Ten participants also underwent tendon transfers. The population’s mean age at time of injury was 27.3 years. Three patients were female. Motor vehicle accidents were the most common cause of injury (31%). Follow-up data at 24 months were unavailable for three patients.
Participants’ median ARAT total score significantly improved from 16.5 at baseline to 34.0 at 24 months. Median GRT total score significantly improved from 35.0 at baseline to 125.2 at 24 months. The population’s mean total SCIM score and mobility in the room and toilet SCIM score improved by more than the minimal detectable change and the minimal clinically important difference. The mean self-care SCIM score improved by more than the minimal detectable change between baseline and 24 months.
The researchers observed six adverse events related to the surgery, but none had sustained functional consequences. No patients had an increase in musculoskeletal or neuropathic pain. Four of the 50 nerve transfers with 24-month follow-up failed.
A novel technique
“This project is the first to comprehensively examine outcomes for early, multiple nerve transfer surgery in the upper limbs of people with tetraplegia following traumatic spinal cord injury and is the largest prospective series of nerve transfers reported in this population to date,” said Dr. van Zyl and colleagues. Study limitations included the small sample size, the high variability of spinal cord injury patterns, and the potential for the multiple procedures that each participant underwent to confound data analysis.
Future research could explore whether nerve transfers are beneficial at more than 24 months after spinal cord injury, wrote the authors. In addition, it is unclear whether function and strength continue to improve beyond 24 months after surgery.
The study was funded by the Institute for Safety, Compensation, and Recovery Research in Australia. The authors had no competing interests.
SOURCE: van Zyl N et al. Lancet. 2019 Jul 4. doi: 10.1016/S0140-6736(19)31143-2.
The data from van Zyl et al. suggest that nerve transfers restore more natural movement and finer motor control than tendon transfers do, said Elspeth J.R. Hill, MD, PhD, and Ida K. Fox, MD, plastic and reconstructive surgeons at Washington University in St. Louis, in an accompanying editorial. Patients can engage in light activity immediately after surgery, and cortical plasticity enables function to improve over time. Two disadvantages of nerve transfers, however, are that it takes months before new motion can be observed, and years before full strength can be regained.
The heterogeneity of cervical spinal cord injury requires an individualized approach to surgical assessment and management, they continued. Physicians and patients should make treatment decisions collaboratively. “We envisage a role for nerve transfers in settings where the intensive therapy and immobilization required to optimize complementary tendon transfers are unavailable,” wrote Dr. Hill and Dr. Fox.
Continuing research will be necessary to improve surgical technique and outcomes. “This research should include efforts to compare nerve transfer with tendon transfer, find the optimal timing of such surgeries, and determine which approach produces the greatest functional improvement,” they wrote. “Detailed study of the reasons for nerve transfer failure is also required, as is improving our understanding of the effects of biopsychosocial factors, including access to information and care, psychological readiness, and social support, on patient decision making and outcomes.”
Nerve transfers are a “huge advance” in the restoration of function after spinal cord injury, the authors added. “Surgeons who integrate nerve transfers into their spinal cord injury practice should take a careful and measured approach and rigorously study and disseminate their outcomes to advance this growing field,” they concluded.
The data from van Zyl et al. suggest that nerve transfers restore more natural movement and finer motor control than tendon transfers do, said Elspeth J.R. Hill, MD, PhD, and Ida K. Fox, MD, plastic and reconstructive surgeons at Washington University in St. Louis, in an accompanying editorial. Patients can engage in light activity immediately after surgery, and cortical plasticity enables function to improve over time. Two disadvantages of nerve transfers, however, are that it takes months before new motion can be observed, and years before full strength can be regained.
The heterogeneity of cervical spinal cord injury requires an individualized approach to surgical assessment and management, they continued. Physicians and patients should make treatment decisions collaboratively. “We envisage a role for nerve transfers in settings where the intensive therapy and immobilization required to optimize complementary tendon transfers are unavailable,” wrote Dr. Hill and Dr. Fox.
Continuing research will be necessary to improve surgical technique and outcomes. “This research should include efforts to compare nerve transfer with tendon transfer, find the optimal timing of such surgeries, and determine which approach produces the greatest functional improvement,” they wrote. “Detailed study of the reasons for nerve transfer failure is also required, as is improving our understanding of the effects of biopsychosocial factors, including access to information and care, psychological readiness, and social support, on patient decision making and outcomes.”
Nerve transfers are a “huge advance” in the restoration of function after spinal cord injury, the authors added. “Surgeons who integrate nerve transfers into their spinal cord injury practice should take a careful and measured approach and rigorously study and disseminate their outcomes to advance this growing field,” they concluded.
The data from van Zyl et al. suggest that nerve transfers restore more natural movement and finer motor control than tendon transfers do, said Elspeth J.R. Hill, MD, PhD, and Ida K. Fox, MD, plastic and reconstructive surgeons at Washington University in St. Louis, in an accompanying editorial. Patients can engage in light activity immediately after surgery, and cortical plasticity enables function to improve over time. Two disadvantages of nerve transfers, however, are that it takes months before new motion can be observed, and years before full strength can be regained.
The heterogeneity of cervical spinal cord injury requires an individualized approach to surgical assessment and management, they continued. Physicians and patients should make treatment decisions collaboratively. “We envisage a role for nerve transfers in settings where the intensive therapy and immobilization required to optimize complementary tendon transfers are unavailable,” wrote Dr. Hill and Dr. Fox.
Continuing research will be necessary to improve surgical technique and outcomes. “This research should include efforts to compare nerve transfer with tendon transfer, find the optimal timing of such surgeries, and determine which approach produces the greatest functional improvement,” they wrote. “Detailed study of the reasons for nerve transfer failure is also required, as is improving our understanding of the effects of biopsychosocial factors, including access to information and care, psychological readiness, and social support, on patient decision making and outcomes.”
Nerve transfers are a “huge advance” in the restoration of function after spinal cord injury, the authors added. “Surgeons who integrate nerve transfers into their spinal cord injury practice should take a careful and measured approach and rigorously study and disseminate their outcomes to advance this growing field,” they concluded.
according to research published online July 4 ahead of print in the Lancet. Combining nerve transfer with tendon transfer may maximize the functional benefit of surgery.
The loss of upper extremity function after cervical spinal cord injury can reduce independence and social and vocational engagement. People with tetraplegia rank improvement in hand function as their most important goal. Tendon transfers have been the traditional method of restoring function, but interest in nerve transfers has been increasing with the publication of successful results. Nerve transfers can reanimate several muscles at once and require a smaller incision and shorter immobilization, compared with tendon transfers.
Injury had occurred less than 18 months previously
Natasha van Zyl, MBBS, a plastic and reconstructive surgeon at Austin Health in Melbourne, and colleagues conducted a prospective case series to examine the clinical and functional outcomes of nerve transfer surgery for the reanimation of upper limb function in patients with tetraplegia. The investigators also sought to compare these outcomes with published outcomes for tendon transfer surgery.
Between April 14, 2014, and Nov. 22, 2018, Dr. van Zyl and colleagues recruited consecutive patients of any age with early cervical spinal cord injury of motor level C5 and below. Injury was required to have occurred fewer than 18 months before enrollment. Eligible participants had been referred to a single center for upper extremity reanimation and were considered candidates for nerve transfer.
Every participant underwent single or multiple nerve transfers in one or both upper limbs, and some participants also underwent tendon transfers. The goal of surgery was the restoration of elbow extension, grasp, pinch, and hand opening. An independent assessor evaluated participants at baseline and at 12 months and 24 months after surgery. The primary outcome measures were the action research arm test (ARAT), the grasp release test (GRT), and the spinal cord independence measure (SCIM).
Grasp function improved significantly
Dr. van Zyl and colleagues recruited 16 participants with traumatic spinal cord injury who underwent 59 nerve transfers. Ten participants also underwent tendon transfers. The population’s mean age at time of injury was 27.3 years. Three patients were female. Motor vehicle accidents were the most common cause of injury (31%). Follow-up data at 24 months were unavailable for three patients.
Participants’ median ARAT total score significantly improved from 16.5 at baseline to 34.0 at 24 months. Median GRT total score significantly improved from 35.0 at baseline to 125.2 at 24 months. The population’s mean total SCIM score and mobility in the room and toilet SCIM score improved by more than the minimal detectable change and the minimal clinically important difference. The mean self-care SCIM score improved by more than the minimal detectable change between baseline and 24 months.
The researchers observed six adverse events related to the surgery, but none had sustained functional consequences. No patients had an increase in musculoskeletal or neuropathic pain. Four of the 50 nerve transfers with 24-month follow-up failed.
A novel technique
“This project is the first to comprehensively examine outcomes for early, multiple nerve transfer surgery in the upper limbs of people with tetraplegia following traumatic spinal cord injury and is the largest prospective series of nerve transfers reported in this population to date,” said Dr. van Zyl and colleagues. Study limitations included the small sample size, the high variability of spinal cord injury patterns, and the potential for the multiple procedures that each participant underwent to confound data analysis.
Future research could explore whether nerve transfers are beneficial at more than 24 months after spinal cord injury, wrote the authors. In addition, it is unclear whether function and strength continue to improve beyond 24 months after surgery.
The study was funded by the Institute for Safety, Compensation, and Recovery Research in Australia. The authors had no competing interests.
SOURCE: van Zyl N et al. Lancet. 2019 Jul 4. doi: 10.1016/S0140-6736(19)31143-2.
according to research published online July 4 ahead of print in the Lancet. Combining nerve transfer with tendon transfer may maximize the functional benefit of surgery.
The loss of upper extremity function after cervical spinal cord injury can reduce independence and social and vocational engagement. People with tetraplegia rank improvement in hand function as their most important goal. Tendon transfers have been the traditional method of restoring function, but interest in nerve transfers has been increasing with the publication of successful results. Nerve transfers can reanimate several muscles at once and require a smaller incision and shorter immobilization, compared with tendon transfers.
Injury had occurred less than 18 months previously
Natasha van Zyl, MBBS, a plastic and reconstructive surgeon at Austin Health in Melbourne, and colleagues conducted a prospective case series to examine the clinical and functional outcomes of nerve transfer surgery for the reanimation of upper limb function in patients with tetraplegia. The investigators also sought to compare these outcomes with published outcomes for tendon transfer surgery.
Between April 14, 2014, and Nov. 22, 2018, Dr. van Zyl and colleagues recruited consecutive patients of any age with early cervical spinal cord injury of motor level C5 and below. Injury was required to have occurred fewer than 18 months before enrollment. Eligible participants had been referred to a single center for upper extremity reanimation and were considered candidates for nerve transfer.
Every participant underwent single or multiple nerve transfers in one or both upper limbs, and some participants also underwent tendon transfers. The goal of surgery was the restoration of elbow extension, grasp, pinch, and hand opening. An independent assessor evaluated participants at baseline and at 12 months and 24 months after surgery. The primary outcome measures were the action research arm test (ARAT), the grasp release test (GRT), and the spinal cord independence measure (SCIM).
Grasp function improved significantly
Dr. van Zyl and colleagues recruited 16 participants with traumatic spinal cord injury who underwent 59 nerve transfers. Ten participants also underwent tendon transfers. The population’s mean age at time of injury was 27.3 years. Three patients were female. Motor vehicle accidents were the most common cause of injury (31%). Follow-up data at 24 months were unavailable for three patients.
Participants’ median ARAT total score significantly improved from 16.5 at baseline to 34.0 at 24 months. Median GRT total score significantly improved from 35.0 at baseline to 125.2 at 24 months. The population’s mean total SCIM score and mobility in the room and toilet SCIM score improved by more than the minimal detectable change and the minimal clinically important difference. The mean self-care SCIM score improved by more than the minimal detectable change between baseline and 24 months.
The researchers observed six adverse events related to the surgery, but none had sustained functional consequences. No patients had an increase in musculoskeletal or neuropathic pain. Four of the 50 nerve transfers with 24-month follow-up failed.
A novel technique
“This project is the first to comprehensively examine outcomes for early, multiple nerve transfer surgery in the upper limbs of people with tetraplegia following traumatic spinal cord injury and is the largest prospective series of nerve transfers reported in this population to date,” said Dr. van Zyl and colleagues. Study limitations included the small sample size, the high variability of spinal cord injury patterns, and the potential for the multiple procedures that each participant underwent to confound data analysis.
Future research could explore whether nerve transfers are beneficial at more than 24 months after spinal cord injury, wrote the authors. In addition, it is unclear whether function and strength continue to improve beyond 24 months after surgery.
The study was funded by the Institute for Safety, Compensation, and Recovery Research in Australia. The authors had no competing interests.
SOURCE: van Zyl N et al. Lancet. 2019 Jul 4. doi: 10.1016/S0140-6736(19)31143-2.
FROM LANCET
Can serum inflammatory markers predict concussion recovery?
Levels of interleukin-6 (IL-6) and IL-1 receptor antagonist (IL-1RA) are significantly elevated 6 hours after concussion, and higher IL-6 levels are associated with slower recovery, according to a study of 41 high school and college football players with concussion. The findings were published online ahead of print July 3 in Neurology.
“With so many people sustaining concussions and a sizeable number of them having prolonged symptoms and recovery, any tools we can develop to help determine who would be at greater risk of problems would be very beneficial,” said study author Timothy B. Meier, PhD, assistant professor of neurosurgery at the Medical College of Wisconsin in Milwaukee, in a news release. “These results are a crucial first step.”
Symptoms of sport-related concussion typically resolve within 1-2 weeks but may last longer. Although prior studies have focused on biomarkers that are specific to brain injury, nonspecific inflammatory markers also may hold promise in predicting recovery after a mild traumatic brain injury, the authors said.
To examine whether acute elevations in serum inflammatory markers predict symptom recovery following sport-related concussion, Dr. Meier and his research colleagues enrolled 857 high school and college football players into a prospective cohort study. They included in their analyses 41 concussed athletes and 43 matched control athletes with an average age of 18 years. None of the concussed athletes lost consciousness, two had posttraumatic amnesia, and one had retrograde amnesia. The concussed athletes had a mean symptom duration of 8.86 days.
The researchers measured serum levels of IL-6, IL-1RA, IL-1 beta, IL-10, tumor necrosis factor, C-reactive protein, and interferon-gamma and recorded Sport Concussion Assessment Tool, 3rd edition, symptom severity scores.
Participants with concussion underwent testing at the start of the season, within 6 hours of injury, 24-48 hours after injury, and at 8, 15, and 45 days after injury. Control athletes underwent testing at similar times.
Among athletes with concussion, IL-1RA and IL-6 were elevated at 6 hours, compared with all other postinjury visits and with controls. IL-6 and IL-1RA significantly discriminated concussed from control athletes at 6 hours postconcussion with an area under the receiver operating characteristic curve of 0.79 for IL-6 and 0.79 for IL-1RA. Furthermore, IL-6 levels at 6 hours significantly correlated with symptom duration, “with a 1-unit increase in natural log-transformed IL-6 associated with 39% lower hazard of symptom recovery,” the researchers reported.
The extent to which these results generalize to females, youth athletes, or athletes who develop postconcussion syndrome is unclear, and larger studies may be needed to adequately assess inflammatory markers as clinical biomarkers of sport-related concussion, the authors noted.
“Eventually, these results may help us better understand the relationship between injury and inflammation and potentially lead to new treatments,” Dr. Meier said.
The research was supported by the U.S. Department of Defense, National Institute of Neurological Disorders and Stroke, National Institute of General Medical Sciences, National Institute of Mental Health, and the National Center for Advancing Translational Sciences. The authors had no relevant disclosures.
SOURCE: Nitta ME et al. Neurology. 2019 Jul 3. doi: 10.1212/WNL.0000000000007864.
Levels of interleukin-6 (IL-6) and IL-1 receptor antagonist (IL-1RA) are significantly elevated 6 hours after concussion, and higher IL-6 levels are associated with slower recovery, according to a study of 41 high school and college football players with concussion. The findings were published online ahead of print July 3 in Neurology.
“With so many people sustaining concussions and a sizeable number of them having prolonged symptoms and recovery, any tools we can develop to help determine who would be at greater risk of problems would be very beneficial,” said study author Timothy B. Meier, PhD, assistant professor of neurosurgery at the Medical College of Wisconsin in Milwaukee, in a news release. “These results are a crucial first step.”
Symptoms of sport-related concussion typically resolve within 1-2 weeks but may last longer. Although prior studies have focused on biomarkers that are specific to brain injury, nonspecific inflammatory markers also may hold promise in predicting recovery after a mild traumatic brain injury, the authors said.
To examine whether acute elevations in serum inflammatory markers predict symptom recovery following sport-related concussion, Dr. Meier and his research colleagues enrolled 857 high school and college football players into a prospective cohort study. They included in their analyses 41 concussed athletes and 43 matched control athletes with an average age of 18 years. None of the concussed athletes lost consciousness, two had posttraumatic amnesia, and one had retrograde amnesia. The concussed athletes had a mean symptom duration of 8.86 days.
The researchers measured serum levels of IL-6, IL-1RA, IL-1 beta, IL-10, tumor necrosis factor, C-reactive protein, and interferon-gamma and recorded Sport Concussion Assessment Tool, 3rd edition, symptom severity scores.
Participants with concussion underwent testing at the start of the season, within 6 hours of injury, 24-48 hours after injury, and at 8, 15, and 45 days after injury. Control athletes underwent testing at similar times.
Among athletes with concussion, IL-1RA and IL-6 were elevated at 6 hours, compared with all other postinjury visits and with controls. IL-6 and IL-1RA significantly discriminated concussed from control athletes at 6 hours postconcussion with an area under the receiver operating characteristic curve of 0.79 for IL-6 and 0.79 for IL-1RA. Furthermore, IL-6 levels at 6 hours significantly correlated with symptom duration, “with a 1-unit increase in natural log-transformed IL-6 associated with 39% lower hazard of symptom recovery,” the researchers reported.
The extent to which these results generalize to females, youth athletes, or athletes who develop postconcussion syndrome is unclear, and larger studies may be needed to adequately assess inflammatory markers as clinical biomarkers of sport-related concussion, the authors noted.
“Eventually, these results may help us better understand the relationship between injury and inflammation and potentially lead to new treatments,” Dr. Meier said.
The research was supported by the U.S. Department of Defense, National Institute of Neurological Disorders and Stroke, National Institute of General Medical Sciences, National Institute of Mental Health, and the National Center for Advancing Translational Sciences. The authors had no relevant disclosures.
SOURCE: Nitta ME et al. Neurology. 2019 Jul 3. doi: 10.1212/WNL.0000000000007864.
Levels of interleukin-6 (IL-6) and IL-1 receptor antagonist (IL-1RA) are significantly elevated 6 hours after concussion, and higher IL-6 levels are associated with slower recovery, according to a study of 41 high school and college football players with concussion. The findings were published online ahead of print July 3 in Neurology.
“With so many people sustaining concussions and a sizeable number of them having prolonged symptoms and recovery, any tools we can develop to help determine who would be at greater risk of problems would be very beneficial,” said study author Timothy B. Meier, PhD, assistant professor of neurosurgery at the Medical College of Wisconsin in Milwaukee, in a news release. “These results are a crucial first step.”
Symptoms of sport-related concussion typically resolve within 1-2 weeks but may last longer. Although prior studies have focused on biomarkers that are specific to brain injury, nonspecific inflammatory markers also may hold promise in predicting recovery after a mild traumatic brain injury, the authors said.
To examine whether acute elevations in serum inflammatory markers predict symptom recovery following sport-related concussion, Dr. Meier and his research colleagues enrolled 857 high school and college football players into a prospective cohort study. They included in their analyses 41 concussed athletes and 43 matched control athletes with an average age of 18 years. None of the concussed athletes lost consciousness, two had posttraumatic amnesia, and one had retrograde amnesia. The concussed athletes had a mean symptom duration of 8.86 days.
The researchers measured serum levels of IL-6, IL-1RA, IL-1 beta, IL-10, tumor necrosis factor, C-reactive protein, and interferon-gamma and recorded Sport Concussion Assessment Tool, 3rd edition, symptom severity scores.
Participants with concussion underwent testing at the start of the season, within 6 hours of injury, 24-48 hours after injury, and at 8, 15, and 45 days after injury. Control athletes underwent testing at similar times.
Among athletes with concussion, IL-1RA and IL-6 were elevated at 6 hours, compared with all other postinjury visits and with controls. IL-6 and IL-1RA significantly discriminated concussed from control athletes at 6 hours postconcussion with an area under the receiver operating characteristic curve of 0.79 for IL-6 and 0.79 for IL-1RA. Furthermore, IL-6 levels at 6 hours significantly correlated with symptom duration, “with a 1-unit increase in natural log-transformed IL-6 associated with 39% lower hazard of symptom recovery,” the researchers reported.
The extent to which these results generalize to females, youth athletes, or athletes who develop postconcussion syndrome is unclear, and larger studies may be needed to adequately assess inflammatory markers as clinical biomarkers of sport-related concussion, the authors noted.
“Eventually, these results may help us better understand the relationship between injury and inflammation and potentially lead to new treatments,” Dr. Meier said.
The research was supported by the U.S. Department of Defense, National Institute of Neurological Disorders and Stroke, National Institute of General Medical Sciences, National Institute of Mental Health, and the National Center for Advancing Translational Sciences. The authors had no relevant disclosures.
SOURCE: Nitta ME et al. Neurology. 2019 Jul 3. doi: 10.1212/WNL.0000000000007864.
FROM NEUROLOGY
Key clinical point: Serum biomarkers of inflammation may help identify which athletes will take longer to recover after a sport-related concussion.
Major finding: IL-6 and IL-1RA significantly discriminated concussed from control athletes at 6 hours postconcussion with an area under the receiver operating characteristic curve of 0.79 for IL-6 and 0.79 for IL-1RA. Furthermore, IL-6 levels at 6 hours significantly correlated with symptom duration.
Study details: A prospective cohort study of high school and college football players. The analyses included 41 concussed athletes and 43 matched control athletes with an average age of about 18 years.
Disclosures: The research was supported by the U.S. Department of Defense, National Institute of Neurological Disorders and Stroke, National Institute of General Medical Sciences, National Institute of Mental Health, and the National Center for Advancing Translational Sciences. The authors had no relevant disclosures.
Source: Nitta ME et al. Neurology. 2019 Jul 3. doi: 10.1212/WNL.0000000000007864.