Neurology

The odds of adulthood insomnia are significantly higher among those with childhood behavioral problems, according to research published in JAMA Network Open.

klebercordeiro/Getty Images

Yohannes Adama Melaku, MPH, PhD, of the Adelaide (Australia) Institute for Sleep Health at Flinders University and coauthors drew data from the 1970 UK Birth Cohort Study. This study followed an initial cohort of 16,571 babies who were born during a single week, with follow-up at ages 5, 10, 16, 26, 30, 38, 42, and 46 years. For the purposes of this study, the investigators looked at participants who, at 42 years of age, were alive and not lost to follow-up and who responded to an invitation to be interviewed; the sample sizes in the analysis were 8,050 participants aged 5 years, 9,090 participants aged 10 years, 9,653 participants aged 16 years, and 9,841 participants aged 42 years.

Behavior was measured at ages 5 years and 16 years using the Rutter Behavioral Scale (RBS) and at age 10 years using a visual analog scale, and insomnia symptoms were assessed through interviewing participants in adulthood about duration of sleep, difficulty initiating sleep, difficulty maintaining sleep, and not feeling rested on waking. Participants were organized into normal behavior (less than or equal to 80th percentile on RBS), moderate behavioral problems (greater than the 80th percentile but less than or equal to the 95th percentile), and severe behavioral problems (above 95th percentile). The investigators then devised two models for their analysis: Model 1 adjusted for sex, parent’s social class and educational level, marital status, educational status, and social class, and model 2 adjusted for physical activity level and body mass index (BMI) trajectory (from 10 to 42 years), perceived health status, and number of noncommunicable diseases, although this latter model yielded fewer statistically significant results in some analyses.

Odds for difficulty initiating or maintaining sleep as an adult was increased among participants with severe behavioral problems at age 5 years in model 1 (adjusted odds ratio, 1.50; 95% confidence interval, 1.14-1.96; P = .004), as well as for those with severe problems at 10 years (aOR, 1.30; 95% CI, 1.14-1.63; P = .001), and at 16 years (aOR, 2.17; 95% CI, 1.59-2.91; P less than .001). The aORs also were higher individually for difficulty initiating sleep and for difficulty maintaining sleep in all age groups.

The association with adulthood insomnia was stronger in participants with externalizing behavioral problems such as lying, bullying, restlessness, and fighting than it was in those with internalizing behavioral problems such as worry, fearfulness, and solitariness.

“Although early sleep problems should be identified, we should additionally identify children with moderate to severe behavioral problems that persist throughout childhood as potential beneficiaries of early intervention with a sleep health focus,” the authors wrote.

One of the study’s limitations was a lack of standardized insomnia measures in the cohort study; however, the researchers suggested that the symptoms included reflect those of standardized measures and diagnostic criteria.

“This study is the first, to our knowledge, to suggest an unfavorable association of early-life behavioral problems with adulthood sleep health, underlining the importance of treating behavioral problems in children and addressing insomnia from a life-course perspective,” they concluded.

No study sponsor was identified. The authors reported no relevant financial disclosures.
 

[email protected]

SOURCE: Melaku YA et al. JAMA Netw Open. 2019 Sep 6. doi: 10.1001/jamanetworkopen.2019.10861.

The odds of adulthood insomnia are significantly higher among those with childhood behavioral problems, according to research published in JAMA Network Open.

klebercordeiro/Getty Images

Yohannes Adama Melaku, MPH, PhD, of the Adelaide (Australia) Institute for Sleep Health at Flinders University and coauthors drew data from the 1970 UK Birth Cohort Study. This study followed an initial cohort of 16,571 babies who were born during a single week, with follow-up at ages 5, 10, 16, 26, 30, 38, 42, and 46 years. For the purposes of this study, the investigators looked at participants who, at 42 years of age, were alive and not lost to follow-up and who responded to an invitation to be interviewed; the sample sizes in the analysis were 8,050 participants aged 5 years, 9,090 participants aged 10 years, 9,653 participants aged 16 years, and 9,841 participants aged 42 years.

Behavior was measured at ages 5 years and 16 years using the Rutter Behavioral Scale (RBS) and at age 10 years using a visual analog scale, and insomnia symptoms were assessed through interviewing participants in adulthood about duration of sleep, difficulty initiating sleep, difficulty maintaining sleep, and not feeling rested on waking. Participants were organized into normal behavior (less than or equal to 80th percentile on RBS), moderate behavioral problems (greater than the 80th percentile but less than or equal to the 95th percentile), and severe behavioral problems (above 95th percentile). The investigators then devised two models for their analysis: Model 1 adjusted for sex, parent’s social class and educational level, marital status, educational status, and social class, and model 2 adjusted for physical activity level and body mass index (BMI) trajectory (from 10 to 42 years), perceived health status, and number of noncommunicable diseases, although this latter model yielded fewer statistically significant results in some analyses.

Odds for difficulty initiating or maintaining sleep as an adult was increased among participants with severe behavioral problems at age 5 years in model 1 (adjusted odds ratio, 1.50; 95% confidence interval, 1.14-1.96; P = .004), as well as for those with severe problems at 10 years (aOR, 1.30; 95% CI, 1.14-1.63; P = .001), and at 16 years (aOR, 2.17; 95% CI, 1.59-2.91; P less than .001). The aORs also were higher individually for difficulty initiating sleep and for difficulty maintaining sleep in all age groups.

The association with adulthood insomnia was stronger in participants with externalizing behavioral problems such as lying, bullying, restlessness, and fighting than it was in those with internalizing behavioral problems such as worry, fearfulness, and solitariness.

“Although early sleep problems should be identified, we should additionally identify children with moderate to severe behavioral problems that persist throughout childhood as potential beneficiaries of early intervention with a sleep health focus,” the authors wrote.

One of the study’s limitations was a lack of standardized insomnia measures in the cohort study; however, the researchers suggested that the symptoms included reflect those of standardized measures and diagnostic criteria.

“This study is the first, to our knowledge, to suggest an unfavorable association of early-life behavioral problems with adulthood sleep health, underlining the importance of treating behavioral problems in children and addressing insomnia from a life-course perspective,” they concluded.

No study sponsor was identified. The authors reported no relevant financial disclosures.
 

[email protected]

SOURCE: Melaku YA et al. JAMA Netw Open. 2019 Sep 6. doi: 10.1001/jamanetworkopen.2019.10861.

The odds of adulthood insomnia are significantly higher among those with childhood behavioral problems, according to research published in JAMA Network Open.

klebercordeiro/Getty Images

Yohannes Adama Melaku, MPH, PhD, of the Adelaide (Australia) Institute for Sleep Health at Flinders University and coauthors drew data from the 1970 UK Birth Cohort Study. This study followed an initial cohort of 16,571 babies who were born during a single week, with follow-up at ages 5, 10, 16, 26, 30, 38, 42, and 46 years. For the purposes of this study, the investigators looked at participants who, at 42 years of age, were alive and not lost to follow-up and who responded to an invitation to be interviewed; the sample sizes in the analysis were 8,050 participants aged 5 years, 9,090 participants aged 10 years, 9,653 participants aged 16 years, and 9,841 participants aged 42 years.

Behavior was measured at ages 5 years and 16 years using the Rutter Behavioral Scale (RBS) and at age 10 years using a visual analog scale, and insomnia symptoms were assessed through interviewing participants in adulthood about duration of sleep, difficulty initiating sleep, difficulty maintaining sleep, and not feeling rested on waking. Participants were organized into normal behavior (less than or equal to 80th percentile on RBS), moderate behavioral problems (greater than the 80th percentile but less than or equal to the 95th percentile), and severe behavioral problems (above 95th percentile). The investigators then devised two models for their analysis: Model 1 adjusted for sex, parent’s social class and educational level, marital status, educational status, and social class, and model 2 adjusted for physical activity level and body mass index (BMI) trajectory (from 10 to 42 years), perceived health status, and number of noncommunicable diseases, although this latter model yielded fewer statistically significant results in some analyses.

Odds for difficulty initiating or maintaining sleep as an adult was increased among participants with severe behavioral problems at age 5 years in model 1 (adjusted odds ratio, 1.50; 95% confidence interval, 1.14-1.96; P = .004), as well as for those with severe problems at 10 years (aOR, 1.30; 95% CI, 1.14-1.63; P = .001), and at 16 years (aOR, 2.17; 95% CI, 1.59-2.91; P less than .001). The aORs also were higher individually for difficulty initiating sleep and for difficulty maintaining sleep in all age groups.

The association with adulthood insomnia was stronger in participants with externalizing behavioral problems such as lying, bullying, restlessness, and fighting than it was in those with internalizing behavioral problems such as worry, fearfulness, and solitariness.

“Although early sleep problems should be identified, we should additionally identify children with moderate to severe behavioral problems that persist throughout childhood as potential beneficiaries of early intervention with a sleep health focus,” the authors wrote.

One of the study’s limitations was a lack of standardized insomnia measures in the cohort study; however, the researchers suggested that the symptoms included reflect those of standardized measures and diagnostic criteria.

“This study is the first, to our knowledge, to suggest an unfavorable association of early-life behavioral problems with adulthood sleep health, underlining the importance of treating behavioral problems in children and addressing insomnia from a life-course perspective,” they concluded.

No study sponsor was identified. The authors reported no relevant financial disclosures.
 

[email protected]

SOURCE: Melaku YA et al. JAMA Netw Open. 2019 Sep 6. doi: 10.1001/jamanetworkopen.2019.10861.

The early infusion of bone marrow cells could help patients recover from acute ischemic stroke, results from a single-arm, phase I trial demonstrated. Unlike autologous mesenchymal stem cells, mononuclear cells (MNCs) do not require passage in culture, which allows for testing in the early poststroke time therapy window.

Courtesy University of Texas, Houston

Bone marrow MNCs are attractive in regenerative medicine studies because they can be rapidly isolated; are enriched with hematopoietic, mesenchymal, and endothelial progenitor cells; and permit autologous applications. “The regenerative potential of bone marrow–derived MNCs is attributed to various mechanisms that impact stroke recovery,” researchers led by Sean I. Savitz, MD, wrote in a study published online Sept. 17 in Stem Cells. “These cells migrate to the site of injury, release cytokines and other trophic factors, decrease proinflammatory and upregulate anti-inflammatory pathways, and enhance angiogenesis, neurogenesis, and synaptogenesis.”

For the trial, Dr. Savitz, MD, director of the Institute for Stroke and Cerebrovascular Disease at UTHealth, Houston, and colleagues recruited 25 patients to receive an IV dose of their own bone marrow mononuclear cells within 72 hours after stroke onset, a time frame supported by previous preclinical studies. They followed the patients for 1 year and compared the results with a control group of 185 patients who received conventional poststroke treatment. Primary outcomes were study-related serious adverse events and the proportion of patients successfully completing study intervention.

The researchers reported results from 25 patients who received bone marrow MNCs. The mean age of patients in the MNC and control groups were 61 and 63 years, respectively, 53% were female, and 69% were white. No study-related adverse events were observed in the MNC group, but three (12%) had infarct expansion between enrollment and harvest and underwent elective hemicraniectomy after cell infusion.

Advanced magnetic resonance imaging revealed that the average mean fractional anisotropy (FA), a measure of structural integrity and directional coherence of axonal fibers, within the ipsilesional pons was decreased between 1 and 3 months after stroke, “which translated to a relative FA [rFA] comparable with prior reports at this time point,” the researchers wrote. “However, by 6 months, mean rFA began to increase and by 2 years it was significantly higher than at 1 month. This increasing trend in rFA may imply an increase in axonal and fiber coherence as well as thickness in myelin sheets, suggesting microstructural repair. However, without a comparable group of stroke patients not treated with MNCs, we cannot directly ascribe the white matter changes to MNC treatment.”

In light of the findings, the researchers concluded that MNCs “pose no additional harm in ischemic stroke patients when given during the acute phase, doses up to 10 million cells per kilogram are tolerated, and it is feasible to perform a bone marrow harvest and reinfusion of MNCs for a wide range of stroke patients. Well-designed RCTs are needed to further assess safety and efficacy of this novel investigational approach to enhance stroke recovery.”

The study was supported by grants from the National Institutes of Health. Dr. Savitz and many of his coauthors disclosed having numerous financial ties to the pharmaceutical and biotechnology industries.

[email protected]

SOURCE: Vahidy F et al. Stem Cells. 2019 Sept. 17.

The early infusion of bone marrow cells could help patients recover from acute ischemic stroke, results from a single-arm, phase I trial demonstrated. Unlike autologous mesenchymal stem cells, mononuclear cells (MNCs) do not require passage in culture, which allows for testing in the early poststroke time therapy window.

Courtesy University of Texas, Houston

Bone marrow MNCs are attractive in regenerative medicine studies because they can be rapidly isolated; are enriched with hematopoietic, mesenchymal, and endothelial progenitor cells; and permit autologous applications. “The regenerative potential of bone marrow–derived MNCs is attributed to various mechanisms that impact stroke recovery,” researchers led by Sean I. Savitz, MD, wrote in a study published online Sept. 17 in Stem Cells. “These cells migrate to the site of injury, release cytokines and other trophic factors, decrease proinflammatory and upregulate anti-inflammatory pathways, and enhance angiogenesis, neurogenesis, and synaptogenesis.”

For the trial, Dr. Savitz, MD, director of the Institute for Stroke and Cerebrovascular Disease at UTHealth, Houston, and colleagues recruited 25 patients to receive an IV dose of their own bone marrow mononuclear cells within 72 hours after stroke onset, a time frame supported by previous preclinical studies. They followed the patients for 1 year and compared the results with a control group of 185 patients who received conventional poststroke treatment. Primary outcomes were study-related serious adverse events and the proportion of patients successfully completing study intervention.

The researchers reported results from 25 patients who received bone marrow MNCs. The mean age of patients in the MNC and control groups were 61 and 63 years, respectively, 53% were female, and 69% were white. No study-related adverse events were observed in the MNC group, but three (12%) had infarct expansion between enrollment and harvest and underwent elective hemicraniectomy after cell infusion.

Advanced magnetic resonance imaging revealed that the average mean fractional anisotropy (FA), a measure of structural integrity and directional coherence of axonal fibers, within the ipsilesional pons was decreased between 1 and 3 months after stroke, “which translated to a relative FA [rFA] comparable with prior reports at this time point,” the researchers wrote. “However, by 6 months, mean rFA began to increase and by 2 years it was significantly higher than at 1 month. This increasing trend in rFA may imply an increase in axonal and fiber coherence as well as thickness in myelin sheets, suggesting microstructural repair. However, without a comparable group of stroke patients not treated with MNCs, we cannot directly ascribe the white matter changes to MNC treatment.”

In light of the findings, the researchers concluded that MNCs “pose no additional harm in ischemic stroke patients when given during the acute phase, doses up to 10 million cells per kilogram are tolerated, and it is feasible to perform a bone marrow harvest and reinfusion of MNCs for a wide range of stroke patients. Well-designed RCTs are needed to further assess safety and efficacy of this novel investigational approach to enhance stroke recovery.”

The study was supported by grants from the National Institutes of Health. Dr. Savitz and many of his coauthors disclosed having numerous financial ties to the pharmaceutical and biotechnology industries.

[email protected]

SOURCE: Vahidy F et al. Stem Cells. 2019 Sept. 17.

The early infusion of bone marrow cells could help patients recover from acute ischemic stroke, results from a single-arm, phase I trial demonstrated. Unlike autologous mesenchymal stem cells, mononuclear cells (MNCs) do not require passage in culture, which allows for testing in the early poststroke time therapy window.

Courtesy University of Texas, Houston

Bone marrow MNCs are attractive in regenerative medicine studies because they can be rapidly isolated; are enriched with hematopoietic, mesenchymal, and endothelial progenitor cells; and permit autologous applications. “The regenerative potential of bone marrow–derived MNCs is attributed to various mechanisms that impact stroke recovery,” researchers led by Sean I. Savitz, MD, wrote in a study published online Sept. 17 in Stem Cells. “These cells migrate to the site of injury, release cytokines and other trophic factors, decrease proinflammatory and upregulate anti-inflammatory pathways, and enhance angiogenesis, neurogenesis, and synaptogenesis.”

For the trial, Dr. Savitz, MD, director of the Institute for Stroke and Cerebrovascular Disease at UTHealth, Houston, and colleagues recruited 25 patients to receive an IV dose of their own bone marrow mononuclear cells within 72 hours after stroke onset, a time frame supported by previous preclinical studies. They followed the patients for 1 year and compared the results with a control group of 185 patients who received conventional poststroke treatment. Primary outcomes were study-related serious adverse events and the proportion of patients successfully completing study intervention.

The researchers reported results from 25 patients who received bone marrow MNCs. The mean age of patients in the MNC and control groups were 61 and 63 years, respectively, 53% were female, and 69% were white. No study-related adverse events were observed in the MNC group, but three (12%) had infarct expansion between enrollment and harvest and underwent elective hemicraniectomy after cell infusion.

Advanced magnetic resonance imaging revealed that the average mean fractional anisotropy (FA), a measure of structural integrity and directional coherence of axonal fibers, within the ipsilesional pons was decreased between 1 and 3 months after stroke, “which translated to a relative FA [rFA] comparable with prior reports at this time point,” the researchers wrote. “However, by 6 months, mean rFA began to increase and by 2 years it was significantly higher than at 1 month. This increasing trend in rFA may imply an increase in axonal and fiber coherence as well as thickness in myelin sheets, suggesting microstructural repair. However, without a comparable group of stroke patients not treated with MNCs, we cannot directly ascribe the white matter changes to MNC treatment.”

In light of the findings, the researchers concluded that MNCs “pose no additional harm in ischemic stroke patients when given during the acute phase, doses up to 10 million cells per kilogram are tolerated, and it is feasible to perform a bone marrow harvest and reinfusion of MNCs for a wide range of stroke patients. Well-designed RCTs are needed to further assess safety and efficacy of this novel investigational approach to enhance stroke recovery.”

The study was supported by grants from the National Institutes of Health. Dr. Savitz and many of his coauthors disclosed having numerous financial ties to the pharmaceutical and biotechnology industries.

[email protected]

SOURCE: Vahidy F et al. Stem Cells. 2019 Sept. 17.

Of eight recommended prevention strategies for repeat severe pneumonia in children with neurologic impairment, only one – dental care – was found to be effective, according to findings published in Pediatrics.

Five of the remaining seven strategies – gastrostomy tube placement, chest physiotherapy, outpatient antibiotics before hospitalization, and clinic visit before and after index hospitalization – were associated with increased recurrence, Jody L. Lin, MD, of the department of pediatrics at Stanford (Calif.) University, and colleagues reported. Oral secretion management and gastric acid suppression were associated with increased risk, but to a lesser extent.

The researchers examined the outcomes of the prevention strategies because, although children with neurologic impairment are more susceptible to community-acquired pneumonia, current guidelines are based mostly on expert opinion. The study included 3,632 children aged 21 years or younger with neurologic impairment and at least one hospitalization for pneumonia, who were enrolled in the California Children’s Services program between July 1, 2009, and June 30, 2014.

Propensity-score matching based on factors such as age, sex, household income, as well as characteristics of index hospitalization, showed decreased odds of recurrence only with receipt of dental care (adjusted odds ratio, 0.64; 95% confidence interval, 0.49-0.85), whereas increased odds were seen with other recommended prevention strategies, such as chest physiotherapy (aOR, 2.03; 95% CI, 1.29-3.20), receipt of antibiotics before hospitalization (aOR, 1.42; 95% CI, 1.06-1.92), and clinic visit before (aOR, 1.30; 95% CI, 1.11-1.52) and after index hospitalization (aOR, 1.72; 95% CI, 1.35-2.20).

The greatest increased odds, however, were seen with new gastrostomy tube placement (aOR, 2.15; 95% CI, 1.63-2.85).

The investigators noted that the biggest limitation of this study was the potential for residual confounding by indication even after adjustment, whereby certain interventions were provided to patients deemed more clinically severe to begin with. A strength of the study is its longitudinal nature.

“Our results suggest that more attention should be paid to dental health for children with [neurologic impairment],” the researchers wrote, although they noted that dental care “remains the most common unmet health care need” for children with special health care needs.

The findings also “support a clinical trial of dental care for prevention of severe pneumonia in children with [neurologic impairment] and do not support the widespread use of gastrostomy tubes for that purpose,” they added.

The study was funded by the National Institutes of Health. Dr. Lin received support from the NIH and the Clinical Excellence Research Center. The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Lin JL et al. Pediatrics. 2019 Sep 19. doi: 10.1542/peds.2019-0543.

Of eight recommended prevention strategies for repeat severe pneumonia in children with neurologic impairment, only one – dental care – was found to be effective, according to findings published in Pediatrics.

Five of the remaining seven strategies – gastrostomy tube placement, chest physiotherapy, outpatient antibiotics before hospitalization, and clinic visit before and after index hospitalization – were associated with increased recurrence, Jody L. Lin, MD, of the department of pediatrics at Stanford (Calif.) University, and colleagues reported. Oral secretion management and gastric acid suppression were associated with increased risk, but to a lesser extent.

The researchers examined the outcomes of the prevention strategies because, although children with neurologic impairment are more susceptible to community-acquired pneumonia, current guidelines are based mostly on expert opinion. The study included 3,632 children aged 21 years or younger with neurologic impairment and at least one hospitalization for pneumonia, who were enrolled in the California Children’s Services program between July 1, 2009, and June 30, 2014.

Propensity-score matching based on factors such as age, sex, household income, as well as characteristics of index hospitalization, showed decreased odds of recurrence only with receipt of dental care (adjusted odds ratio, 0.64; 95% confidence interval, 0.49-0.85), whereas increased odds were seen with other recommended prevention strategies, such as chest physiotherapy (aOR, 2.03; 95% CI, 1.29-3.20), receipt of antibiotics before hospitalization (aOR, 1.42; 95% CI, 1.06-1.92), and clinic visit before (aOR, 1.30; 95% CI, 1.11-1.52) and after index hospitalization (aOR, 1.72; 95% CI, 1.35-2.20).

The greatest increased odds, however, were seen with new gastrostomy tube placement (aOR, 2.15; 95% CI, 1.63-2.85).

The investigators noted that the biggest limitation of this study was the potential for residual confounding by indication even after adjustment, whereby certain interventions were provided to patients deemed more clinically severe to begin with. A strength of the study is its longitudinal nature.

“Our results suggest that more attention should be paid to dental health for children with [neurologic impairment],” the researchers wrote, although they noted that dental care “remains the most common unmet health care need” for children with special health care needs.

The findings also “support a clinical trial of dental care for prevention of severe pneumonia in children with [neurologic impairment] and do not support the widespread use of gastrostomy tubes for that purpose,” they added.

The study was funded by the National Institutes of Health. Dr. Lin received support from the NIH and the Clinical Excellence Research Center. The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Lin JL et al. Pediatrics. 2019 Sep 19. doi: 10.1542/peds.2019-0543.

Of eight recommended prevention strategies for repeat severe pneumonia in children with neurologic impairment, only one – dental care – was found to be effective, according to findings published in Pediatrics.

Five of the remaining seven strategies – gastrostomy tube placement, chest physiotherapy, outpatient antibiotics before hospitalization, and clinic visit before and after index hospitalization – were associated with increased recurrence, Jody L. Lin, MD, of the department of pediatrics at Stanford (Calif.) University, and colleagues reported. Oral secretion management and gastric acid suppression were associated with increased risk, but to a lesser extent.

The researchers examined the outcomes of the prevention strategies because, although children with neurologic impairment are more susceptible to community-acquired pneumonia, current guidelines are based mostly on expert opinion. The study included 3,632 children aged 21 years or younger with neurologic impairment and at least one hospitalization for pneumonia, who were enrolled in the California Children’s Services program between July 1, 2009, and June 30, 2014.

Propensity-score matching based on factors such as age, sex, household income, as well as characteristics of index hospitalization, showed decreased odds of recurrence only with receipt of dental care (adjusted odds ratio, 0.64; 95% confidence interval, 0.49-0.85), whereas increased odds were seen with other recommended prevention strategies, such as chest physiotherapy (aOR, 2.03; 95% CI, 1.29-3.20), receipt of antibiotics before hospitalization (aOR, 1.42; 95% CI, 1.06-1.92), and clinic visit before (aOR, 1.30; 95% CI, 1.11-1.52) and after index hospitalization (aOR, 1.72; 95% CI, 1.35-2.20).

The greatest increased odds, however, were seen with new gastrostomy tube placement (aOR, 2.15; 95% CI, 1.63-2.85).

The investigators noted that the biggest limitation of this study was the potential for residual confounding by indication even after adjustment, whereby certain interventions were provided to patients deemed more clinically severe to begin with. A strength of the study is its longitudinal nature.

“Our results suggest that more attention should be paid to dental health for children with [neurologic impairment],” the researchers wrote, although they noted that dental care “remains the most common unmet health care need” for children with special health care needs.

The findings also “support a clinical trial of dental care for prevention of severe pneumonia in children with [neurologic impairment] and do not support the widespread use of gastrostomy tubes for that purpose,” they added.

The study was funded by the National Institutes of Health. Dr. Lin received support from the NIH and the Clinical Excellence Research Center. The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Lin JL et al. Pediatrics. 2019 Sep 19. doi: 10.1542/peds.2019-0543.

“Fast MRI,” which allows scans to be taken quickly without sedation, is a “reasonable alternative” to screen certain younger children for traumatic brain injury, a new study found.

gorodenkoff/Getty Images

The fast MRI option has “the potential to eliminate ionizing radiation exposure for thousands of children each year,” the study authors wrote in Pediatrics. “The ability to complete imaging in about 6 minutes, without the need for anesthesia or sedation, suggests that fast MRI is appropriate even in acute settings, where patient throughput is a priority.”

Daniel M. Lindberg, MD, of the University of Colorado at Denver, Aurora, and associates wrote that children make between 600,000 and 1.6 million ED visits in the United States each year for evaluation of possible traumatic brain injury (TBI). While the incidence of clinically significant injury from TBI is low, 20%-70% of these children are exposed to potentially dangerous radiation as they undergo CT.

The new study focuses on fast MRI. Unlike traditional MRI, it doesn’t require children to remain motionless – typically with the help of sedation – to be scanned.

The researchers performed fast MRI in 223 children aged younger than 6 years (median age, 12.6 months; interquartile range, 4.7-32.6) who sought emergency care at a level 1 pediatric trauma center from 2015 to 2018. They had all had CT scans performed.

CT identified TBI in 111 (50%) of the subjects, while fast MRI identified it in 103 (sensitivity, 92.8%; 95% confidence interval, 86.3-96.8). Fast MRI missed six participants with isolated skull fractures and two with subarachnoid hemorrhage; CT missed five participants with subdural hematomas, parenchymal contusions, and subarachnoid hemorrhage.

While the researchers hoped for a higher sensitivity level, they wrote that “we feel that the benefit of avoiding radiation exposure outweighs the concern for missed injury.”

In a commentary, Brett Burstein, MDCM, PhD, MPH, and Christine Saint-Martin, MDCM, MSc, of Montreal Children’s Hospital and McGill University Health Center, also in Montreal, wrote that the study is “well conducted.”

However, they noted that “the reported feasibility reflects a highly selected cohort of stable patients in whom fast MRI is already likely to succeed. Feasibility results in a more generalizable population of head-injured children cannot be extrapolated.”

And, they added, “fast MRI was unavailable for 65 of 299 consenting, eligible patients because of lack of overnight staffing. Although not included among the outcome definitions of imaging time, this would be an important ‘feasibility’ consideration in most centers.”

Dr. Burstein and Dr. Saint-Martin wrote that “centers migrating toward this modality for neuroimaging children with head injuries should still use clinical judgment and highly sensitive, validated clinical decision rules when determining the need for any neuroimaging for head-injured children.”

The study was funded by the Colorado Traumatic Brain Injury Trust Fund (MindSource) and the Colorado Clinical and Translational Sciences Institute. The study and commentary authors reported no relevant financial disclosures.

SOURCES: Lindberg DM et al. Pediatrics. 2019 Sep 18. doi: 10.1542/peds.2019-0419; Burstein B, Saint-Martin C. Pediatrics. 2019 Sep 18. doi: 10.1542/peds.2019-2387.

“Fast MRI,” which allows scans to be taken quickly without sedation, is a “reasonable alternative” to screen certain younger children for traumatic brain injury, a new study found.

gorodenkoff/Getty Images

The fast MRI option has “the potential to eliminate ionizing radiation exposure for thousands of children each year,” the study authors wrote in Pediatrics. “The ability to complete imaging in about 6 minutes, without the need for anesthesia or sedation, suggests that fast MRI is appropriate even in acute settings, where patient throughput is a priority.”

Daniel M. Lindberg, MD, of the University of Colorado at Denver, Aurora, and associates wrote that children make between 600,000 and 1.6 million ED visits in the United States each year for evaluation of possible traumatic brain injury (TBI). While the incidence of clinically significant injury from TBI is low, 20%-70% of these children are exposed to potentially dangerous radiation as they undergo CT.

The new study focuses on fast MRI. Unlike traditional MRI, it doesn’t require children to remain motionless – typically with the help of sedation – to be scanned.

The researchers performed fast MRI in 223 children aged younger than 6 years (median age, 12.6 months; interquartile range, 4.7-32.6) who sought emergency care at a level 1 pediatric trauma center from 2015 to 2018. They had all had CT scans performed.

CT identified TBI in 111 (50%) of the subjects, while fast MRI identified it in 103 (sensitivity, 92.8%; 95% confidence interval, 86.3-96.8). Fast MRI missed six participants with isolated skull fractures and two with subarachnoid hemorrhage; CT missed five participants with subdural hematomas, parenchymal contusions, and subarachnoid hemorrhage.

While the researchers hoped for a higher sensitivity level, they wrote that “we feel that the benefit of avoiding radiation exposure outweighs the concern for missed injury.”

In a commentary, Brett Burstein, MDCM, PhD, MPH, and Christine Saint-Martin, MDCM, MSc, of Montreal Children’s Hospital and McGill University Health Center, also in Montreal, wrote that the study is “well conducted.”

However, they noted that “the reported feasibility reflects a highly selected cohort of stable patients in whom fast MRI is already likely to succeed. Feasibility results in a more generalizable population of head-injured children cannot be extrapolated.”

And, they added, “fast MRI was unavailable for 65 of 299 consenting, eligible patients because of lack of overnight staffing. Although not included among the outcome definitions of imaging time, this would be an important ‘feasibility’ consideration in most centers.”

Dr. Burstein and Dr. Saint-Martin wrote that “centers migrating toward this modality for neuroimaging children with head injuries should still use clinical judgment and highly sensitive, validated clinical decision rules when determining the need for any neuroimaging for head-injured children.”

The study was funded by the Colorado Traumatic Brain Injury Trust Fund (MindSource) and the Colorado Clinical and Translational Sciences Institute. The study and commentary authors reported no relevant financial disclosures.

SOURCES: Lindberg DM et al. Pediatrics. 2019 Sep 18. doi: 10.1542/peds.2019-0419; Burstein B, Saint-Martin C. Pediatrics. 2019 Sep 18. doi: 10.1542/peds.2019-2387.

“Fast MRI,” which allows scans to be taken quickly without sedation, is a “reasonable alternative” to screen certain younger children for traumatic brain injury, a new study found.

gorodenkoff/Getty Images

The fast MRI option has “the potential to eliminate ionizing radiation exposure for thousands of children each year,” the study authors wrote in Pediatrics. “The ability to complete imaging in about 6 minutes, without the need for anesthesia or sedation, suggests that fast MRI is appropriate even in acute settings, where patient throughput is a priority.”

Daniel M. Lindberg, MD, of the University of Colorado at Denver, Aurora, and associates wrote that children make between 600,000 and 1.6 million ED visits in the United States each year for evaluation of possible traumatic brain injury (TBI). While the incidence of clinically significant injury from TBI is low, 20%-70% of these children are exposed to potentially dangerous radiation as they undergo CT.

The new study focuses on fast MRI. Unlike traditional MRI, it doesn’t require children to remain motionless – typically with the help of sedation – to be scanned.

The researchers performed fast MRI in 223 children aged younger than 6 years (median age, 12.6 months; interquartile range, 4.7-32.6) who sought emergency care at a level 1 pediatric trauma center from 2015 to 2018. They had all had CT scans performed.

CT identified TBI in 111 (50%) of the subjects, while fast MRI identified it in 103 (sensitivity, 92.8%; 95% confidence interval, 86.3-96.8). Fast MRI missed six participants with isolated skull fractures and two with subarachnoid hemorrhage; CT missed five participants with subdural hematomas, parenchymal contusions, and subarachnoid hemorrhage.

While the researchers hoped for a higher sensitivity level, they wrote that “we feel that the benefit of avoiding radiation exposure outweighs the concern for missed injury.”

In a commentary, Brett Burstein, MDCM, PhD, MPH, and Christine Saint-Martin, MDCM, MSc, of Montreal Children’s Hospital and McGill University Health Center, also in Montreal, wrote that the study is “well conducted.”

However, they noted that “the reported feasibility reflects a highly selected cohort of stable patients in whom fast MRI is already likely to succeed. Feasibility results in a more generalizable population of head-injured children cannot be extrapolated.”

And, they added, “fast MRI was unavailable for 65 of 299 consenting, eligible patients because of lack of overnight staffing. Although not included among the outcome definitions of imaging time, this would be an important ‘feasibility’ consideration in most centers.”

Dr. Burstein and Dr. Saint-Martin wrote that “centers migrating toward this modality for neuroimaging children with head injuries should still use clinical judgment and highly sensitive, validated clinical decision rules when determining the need for any neuroimaging for head-injured children.”

The study was funded by the Colorado Traumatic Brain Injury Trust Fund (MindSource) and the Colorado Clinical and Translational Sciences Institute. The study and commentary authors reported no relevant financial disclosures.

SOURCES: Lindberg DM et al. Pediatrics. 2019 Sep 18. doi: 10.1542/peds.2019-0419; Burstein B, Saint-Martin C. Pediatrics. 2019 Sep 18. doi: 10.1542/peds.2019-2387.

STOCKHOLM – Just under half of a small cohort of patients with multiple sclerosis (MS) who discontinued disease modifying therapy (DMT) showed signs of relapse or disease progression on magnetic resonance imaging (MRI). Patients who were younger had a higher probability of relapse, according to data presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Of 49 patients who had been on DMT for at least 5 years and had shown no evidence of disease activity (NEDA) during that time, 26 continued to have NEDA through at least 5 years of follow-up, explained Tobias Monschein, MD, of the department of neurology at the Medical University of Vienna.

The cohort of patients had all been taking either interferon beta or glatiramer acetate after a first clinical episode leading to an initial diagnosis of MS. Patients all met Barkhof criteria for MS diagnosis on MRI, and all but six patients had oligoclonal bands found on examination of cerebrospinal fluid.

All patients in the cohort thus met criteria for clinically isolated syndrome (CIS) and MS under the 2017 revisions to the McDonald diagnostic criteria. “To our knowledge, this is the first study determining the risk of disease recurrence in a homogenous cohort of patients with CIS,” reported Dr. Monschein and collaborators.

Before stopping DMT, patients had to show at least 5 years of NEDA status; at that point, patients were offered the opportunity to discontinue medication. The decision to stop or continue taking a DMT was left to individual patient choice, Dr. Monschein said in an interview.

The cohort of patients who decided to discontinue DMT was seen yearly; they received a clinical examination that included expanded disability status scale (EDSS) rating. Patients also received an annual MRI.

Age at DMT discontinuation was predictive of remaining disease free, found Dr. Monschein and collaborators. The 26 patients who continued disease free after DMT discontinuation were a mean 29.7 years old, while patients who had disease recurrence were a mean 22.7 years old.

Looking at age as a dichotomous variable, the investigators found that the 16 patients who were 40 years or older when they stopped DMT had an 18.8% risk of MS recurrence, while the 33 patients younger than 40 years at the time of ceasing DMT had a 60.6% risk of recurrence.

Age, in fact, was the only patient, disease, or therapy characteristic that Dr. Monschein and colleagues found predictive of relapse: “Gender, type of DMT, treatment duration, and CIS symptom did not differ significantly between groups,” they reported.

The data “should not encourage patients to generally stop DMTs after a long NEDA period,” they noted.

In the context of shared patient decision-making, though, the data can inform discussion with patients who wish to discontinue DMTS after long disease-free periods, Dr. Monschein said.

“Physicians should encourage younger people to stay on DMTS despite long lasting NEDA status while in patients [older than] 40 years stopping DMTs together with regular clinical and radiological monitoring could be a reasonable option,” he and his colleagues advised.

Dr. Monschein reported no outside sources of funding and no conflicts of interest.
 

[email protected]

SOURCE: Monschein T et al. ECTRIMS 2019, Abstract P654.

STOCKHOLM – Just under half of a small cohort of patients with multiple sclerosis (MS) who discontinued disease modifying therapy (DMT) showed signs of relapse or disease progression on magnetic resonance imaging (MRI). Patients who were younger had a higher probability of relapse, according to data presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Of 49 patients who had been on DMT for at least 5 years and had shown no evidence of disease activity (NEDA) during that time, 26 continued to have NEDA through at least 5 years of follow-up, explained Tobias Monschein, MD, of the department of neurology at the Medical University of Vienna.

The cohort of patients had all been taking either interferon beta or glatiramer acetate after a first clinical episode leading to an initial diagnosis of MS. Patients all met Barkhof criteria for MS diagnosis on MRI, and all but six patients had oligoclonal bands found on examination of cerebrospinal fluid.

All patients in the cohort thus met criteria for clinically isolated syndrome (CIS) and MS under the 2017 revisions to the McDonald diagnostic criteria. “To our knowledge, this is the first study determining the risk of disease recurrence in a homogenous cohort of patients with CIS,” reported Dr. Monschein and collaborators.

Before stopping DMT, patients had to show at least 5 years of NEDA status; at that point, patients were offered the opportunity to discontinue medication. The decision to stop or continue taking a DMT was left to individual patient choice, Dr. Monschein said in an interview.

The cohort of patients who decided to discontinue DMT was seen yearly; they received a clinical examination that included expanded disability status scale (EDSS) rating. Patients also received an annual MRI.

Age at DMT discontinuation was predictive of remaining disease free, found Dr. Monschein and collaborators. The 26 patients who continued disease free after DMT discontinuation were a mean 29.7 years old, while patients who had disease recurrence were a mean 22.7 years old.

Looking at age as a dichotomous variable, the investigators found that the 16 patients who were 40 years or older when they stopped DMT had an 18.8% risk of MS recurrence, while the 33 patients younger than 40 years at the time of ceasing DMT had a 60.6% risk of recurrence.

Age, in fact, was the only patient, disease, or therapy characteristic that Dr. Monschein and colleagues found predictive of relapse: “Gender, type of DMT, treatment duration, and CIS symptom did not differ significantly between groups,” they reported.

The data “should not encourage patients to generally stop DMTs after a long NEDA period,” they noted.

In the context of shared patient decision-making, though, the data can inform discussion with patients who wish to discontinue DMTS after long disease-free periods, Dr. Monschein said.

“Physicians should encourage younger people to stay on DMTS despite long lasting NEDA status while in patients [older than] 40 years stopping DMTs together with regular clinical and radiological monitoring could be a reasonable option,” he and his colleagues advised.

Dr. Monschein reported no outside sources of funding and no conflicts of interest.
 

[email protected]

SOURCE: Monschein T et al. ECTRIMS 2019, Abstract P654.

STOCKHOLM – Just under half of a small cohort of patients with multiple sclerosis (MS) who discontinued disease modifying therapy (DMT) showed signs of relapse or disease progression on magnetic resonance imaging (MRI). Patients who were younger had a higher probability of relapse, according to data presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Of 49 patients who had been on DMT for at least 5 years and had shown no evidence of disease activity (NEDA) during that time, 26 continued to have NEDA through at least 5 years of follow-up, explained Tobias Monschein, MD, of the department of neurology at the Medical University of Vienna.

The cohort of patients had all been taking either interferon beta or glatiramer acetate after a first clinical episode leading to an initial diagnosis of MS. Patients all met Barkhof criteria for MS diagnosis on MRI, and all but six patients had oligoclonal bands found on examination of cerebrospinal fluid.

All patients in the cohort thus met criteria for clinically isolated syndrome (CIS) and MS under the 2017 revisions to the McDonald diagnostic criteria. “To our knowledge, this is the first study determining the risk of disease recurrence in a homogenous cohort of patients with CIS,” reported Dr. Monschein and collaborators.

Before stopping DMT, patients had to show at least 5 years of NEDA status; at that point, patients were offered the opportunity to discontinue medication. The decision to stop or continue taking a DMT was left to individual patient choice, Dr. Monschein said in an interview.

The cohort of patients who decided to discontinue DMT was seen yearly; they received a clinical examination that included expanded disability status scale (EDSS) rating. Patients also received an annual MRI.

Age at DMT discontinuation was predictive of remaining disease free, found Dr. Monschein and collaborators. The 26 patients who continued disease free after DMT discontinuation were a mean 29.7 years old, while patients who had disease recurrence were a mean 22.7 years old.

Looking at age as a dichotomous variable, the investigators found that the 16 patients who were 40 years or older when they stopped DMT had an 18.8% risk of MS recurrence, while the 33 patients younger than 40 years at the time of ceasing DMT had a 60.6% risk of recurrence.

Age, in fact, was the only patient, disease, or therapy characteristic that Dr. Monschein and colleagues found predictive of relapse: “Gender, type of DMT, treatment duration, and CIS symptom did not differ significantly between groups,” they reported.

The data “should not encourage patients to generally stop DMTs after a long NEDA period,” they noted.

In the context of shared patient decision-making, though, the data can inform discussion with patients who wish to discontinue DMTS after long disease-free periods, Dr. Monschein said.

“Physicians should encourage younger people to stay on DMTS despite long lasting NEDA status while in patients [older than] 40 years stopping DMTs together with regular clinical and radiological monitoring could be a reasonable option,” he and his colleagues advised.

Dr. Monschein reported no outside sources of funding and no conflicts of interest.
 

[email protected]

SOURCE: Monschein T et al. ECTRIMS 2019, Abstract P654.

STOCKHOLM – Children with multiple sclerosis (MS) who are initially treated with one of the newer disease-modifying therapies experienced significantly better disease activity control in terms of clinical and radiologic outcomes, compared with those started on an injectable drug in a large, observational, cohort study conducted by the U.S. Network of Pediatric MS Centers.

This was the first-ever comparative effectiveness study of initial disease-modifying therapies (DMTs) in children with MS. The take-home message was clear: “This study supports the use of newer DMTs early in the course of pediatric MS,” Kristen M. Krysko, MD, said in presenting the results at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

The study was conducted because she and her coinvestigators in the network have noted increasing use of newer DMTs, even as first-line initial treatment, in the setting of pediatric MS. This represents a break with the traditional approach, which entails starting with one of the injectables – either an interferon-beta or glatiramer acetate – because of their more favorable safety profile, then escalating therapy by switching to a newer, more potent agent in the event of a disease breakthrough, explained Dr. Krysko, a clinical fellow in neurology at the University of California, San Francisco.

Until now, there has been only limited evidence on how the newer DMTs stack up in comparison with the injectables in a pediatric MS population. The chief supporting evidence for the harder-hitting initial approach, Dr. Krysko said, has come from a randomized clinical trial in 215 children showing that fingolimod had a lower relapse rate and better MRI outcomes, compared with interferon beta-1a, during 2 years of follow-up, but at the cost of a higher rate of serious adverse events (N Engl J Med. 2018;379[11]:1017-27).

Dr. Krysko presented a prospective study conducted at 12 sites participating in the network. It included 741 children, 85% of whom had MS, with clinically isolated syndrome in the remainder. For 197 patients, the first MS treatment was an injectable. The other 544 children were started on a newer DMT, most often dimethyl fumarate, rituximab, natalizumab, or fingolimod, with a smattering of patients on teriflunomide or ocrelizumab. Patients averaged roughly a 1-year disease history at the time they went on their first DMT and were then followed for a mean of 1.5-1.8 years on that drug.

The primary outcome was the propensity score–matched, annualized relapse rate during follow-up: The annualized rate was 0.2 in the group on newer DMTs, compared with 0.47 with the injectables. The propensity score matching was used because patients were not randomized by treatment. The propensity scores attempted to neutralize potential confounders, including differences in patient demographics, baseline disease activity, and severity of a first pretreatment relapse, she explained.

The between-group difference in adjusted annualized relapse rate was statistically significant. It translated to a 55% reduction in relative risk favoring children on a newer DMT. Moreover, the number needed to treat was impressively low, at 3.7.

“This can be interpreted as [needing] to treat 3.7 individuals with newer rather than injectable DMTs to prevent one relapse,” Dr. Krysko observed.

Secondary endpoints focused on brain MRI findings. The median time to development of new or enlarging T2 hyperintense lesions was 2.79 years with the newer DMTs, compared with 0.42 years with the injectables. The adjusted risk of developing such lesions was reduced by 49% with the newer DMTs.

Similarly, the median time to development of gadolinium-enhancing lesions was 2.25 years with the injectables and had not yet been reached in patients on newer DMTs when the study closed in January 2019.

“Many children on the newer DMTs never experienced a new gadolinium-positive lesion on follow-up,” she noted.

The adjusted risk of developing a new gadolinium-enhancing lesion was 62% lower in the newer-DMT group.

In terms of the safety of the newer DMTs, there were no surprises: The adverse-event profiles mirrored those that have been examined far more extensively in adults, according to Dr. Krysko.

The newer DMTs included oral agents as well as drugs given by intravenous infusion. The IV agents generally resulted in better disease control, compared with the oral agents, as one would expect, she said. The patient numbers were not sufficient to break down the results on an individual drug basis, however, even though this was a relatively large study.

Asked if these study results warranted a sweeping change in clinical practice – a move away from the conventional escalation treatment strategy in children in favor of upfront use of the newer, more effective DMTs – Dr. Krysko said that was tempting in light of a few recent studies in adults showing that even the first treatment can affect important long-term outcomes, including conversion to secondary progressive MS. However, she said she’d like to see additional studies in children that are focused on safety before making widespread changes in treatment strategy, especially because the pediatric MS network study did not include many very young children.

The study was sponsored by the Multiple Sclerosis Society. Dr. Kysko reported having no financial conflicts in regard to the study.

[email protected]

SOURCE: Krysko KM et al. ECTRIMS 2019, abstract 249.

STOCKHOLM – Children with multiple sclerosis (MS) who are initially treated with one of the newer disease-modifying therapies experienced significantly better disease activity control in terms of clinical and radiologic outcomes, compared with those started on an injectable drug in a large, observational, cohort study conducted by the U.S. Network of Pediatric MS Centers.

This was the first-ever comparative effectiveness study of initial disease-modifying therapies (DMTs) in children with MS. The take-home message was clear: “This study supports the use of newer DMTs early in the course of pediatric MS,” Kristen M. Krysko, MD, said in presenting the results at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

The study was conducted because she and her coinvestigators in the network have noted increasing use of newer DMTs, even as first-line initial treatment, in the setting of pediatric MS. This represents a break with the traditional approach, which entails starting with one of the injectables – either an interferon-beta or glatiramer acetate – because of their more favorable safety profile, then escalating therapy by switching to a newer, more potent agent in the event of a disease breakthrough, explained Dr. Krysko, a clinical fellow in neurology at the University of California, San Francisco.

Until now, there has been only limited evidence on how the newer DMTs stack up in comparison with the injectables in a pediatric MS population. The chief supporting evidence for the harder-hitting initial approach, Dr. Krysko said, has come from a randomized clinical trial in 215 children showing that fingolimod had a lower relapse rate and better MRI outcomes, compared with interferon beta-1a, during 2 years of follow-up, but at the cost of a higher rate of serious adverse events (N Engl J Med. 2018;379[11]:1017-27).

Dr. Krysko presented a prospective study conducted at 12 sites participating in the network. It included 741 children, 85% of whom had MS, with clinically isolated syndrome in the remainder. For 197 patients, the first MS treatment was an injectable. The other 544 children were started on a newer DMT, most often dimethyl fumarate, rituximab, natalizumab, or fingolimod, with a smattering of patients on teriflunomide or ocrelizumab. Patients averaged roughly a 1-year disease history at the time they went on their first DMT and were then followed for a mean of 1.5-1.8 years on that drug.

The primary outcome was the propensity score–matched, annualized relapse rate during follow-up: The annualized rate was 0.2 in the group on newer DMTs, compared with 0.47 with the injectables. The propensity score matching was used because patients were not randomized by treatment. The propensity scores attempted to neutralize potential confounders, including differences in patient demographics, baseline disease activity, and severity of a first pretreatment relapse, she explained.

The between-group difference in adjusted annualized relapse rate was statistically significant. It translated to a 55% reduction in relative risk favoring children on a newer DMT. Moreover, the number needed to treat was impressively low, at 3.7.

“This can be interpreted as [needing] to treat 3.7 individuals with newer rather than injectable DMTs to prevent one relapse,” Dr. Krysko observed.

Secondary endpoints focused on brain MRI findings. The median time to development of new or enlarging T2 hyperintense lesions was 2.79 years with the newer DMTs, compared with 0.42 years with the injectables. The adjusted risk of developing such lesions was reduced by 49% with the newer DMTs.

Similarly, the median time to development of gadolinium-enhancing lesions was 2.25 years with the injectables and had not yet been reached in patients on newer DMTs when the study closed in January 2019.

“Many children on the newer DMTs never experienced a new gadolinium-positive lesion on follow-up,” she noted.

The adjusted risk of developing a new gadolinium-enhancing lesion was 62% lower in the newer-DMT group.

In terms of the safety of the newer DMTs, there were no surprises: The adverse-event profiles mirrored those that have been examined far more extensively in adults, according to Dr. Krysko.

The newer DMTs included oral agents as well as drugs given by intravenous infusion. The IV agents generally resulted in better disease control, compared with the oral agents, as one would expect, she said. The patient numbers were not sufficient to break down the results on an individual drug basis, however, even though this was a relatively large study.

Asked if these study results warranted a sweeping change in clinical practice – a move away from the conventional escalation treatment strategy in children in favor of upfront use of the newer, more effective DMTs – Dr. Krysko said that was tempting in light of a few recent studies in adults showing that even the first treatment can affect important long-term outcomes, including conversion to secondary progressive MS. However, she said she’d like to see additional studies in children that are focused on safety before making widespread changes in treatment strategy, especially because the pediatric MS network study did not include many very young children.

The study was sponsored by the Multiple Sclerosis Society. Dr. Kysko reported having no financial conflicts in regard to the study.

[email protected]

SOURCE: Krysko KM et al. ECTRIMS 2019, abstract 249.

STOCKHOLM – Children with multiple sclerosis (MS) who are initially treated with one of the newer disease-modifying therapies experienced significantly better disease activity control in terms of clinical and radiologic outcomes, compared with those started on an injectable drug in a large, observational, cohort study conducted by the U.S. Network of Pediatric MS Centers.

This was the first-ever comparative effectiveness study of initial disease-modifying therapies (DMTs) in children with MS. The take-home message was clear: “This study supports the use of newer DMTs early in the course of pediatric MS,” Kristen M. Krysko, MD, said in presenting the results at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

The study was conducted because she and her coinvestigators in the network have noted increasing use of newer DMTs, even as first-line initial treatment, in the setting of pediatric MS. This represents a break with the traditional approach, which entails starting with one of the injectables – either an interferon-beta or glatiramer acetate – because of their more favorable safety profile, then escalating therapy by switching to a newer, more potent agent in the event of a disease breakthrough, explained Dr. Krysko, a clinical fellow in neurology at the University of California, San Francisco.

Until now, there has been only limited evidence on how the newer DMTs stack up in comparison with the injectables in a pediatric MS population. The chief supporting evidence for the harder-hitting initial approach, Dr. Krysko said, has come from a randomized clinical trial in 215 children showing that fingolimod had a lower relapse rate and better MRI outcomes, compared with interferon beta-1a, during 2 years of follow-up, but at the cost of a higher rate of serious adverse events (N Engl J Med. 2018;379[11]:1017-27).

Dr. Krysko presented a prospective study conducted at 12 sites participating in the network. It included 741 children, 85% of whom had MS, with clinically isolated syndrome in the remainder. For 197 patients, the first MS treatment was an injectable. The other 544 children were started on a newer DMT, most often dimethyl fumarate, rituximab, natalizumab, or fingolimod, with a smattering of patients on teriflunomide or ocrelizumab. Patients averaged roughly a 1-year disease history at the time they went on their first DMT and were then followed for a mean of 1.5-1.8 years on that drug.

The primary outcome was the propensity score–matched, annualized relapse rate during follow-up: The annualized rate was 0.2 in the group on newer DMTs, compared with 0.47 with the injectables. The propensity score matching was used because patients were not randomized by treatment. The propensity scores attempted to neutralize potential confounders, including differences in patient demographics, baseline disease activity, and severity of a first pretreatment relapse, she explained.

The between-group difference in adjusted annualized relapse rate was statistically significant. It translated to a 55% reduction in relative risk favoring children on a newer DMT. Moreover, the number needed to treat was impressively low, at 3.7.

“This can be interpreted as [needing] to treat 3.7 individuals with newer rather than injectable DMTs to prevent one relapse,” Dr. Krysko observed.

Secondary endpoints focused on brain MRI findings. The median time to development of new or enlarging T2 hyperintense lesions was 2.79 years with the newer DMTs, compared with 0.42 years with the injectables. The adjusted risk of developing such lesions was reduced by 49% with the newer DMTs.

Similarly, the median time to development of gadolinium-enhancing lesions was 2.25 years with the injectables and had not yet been reached in patients on newer DMTs when the study closed in January 2019.

“Many children on the newer DMTs never experienced a new gadolinium-positive lesion on follow-up,” she noted.

The adjusted risk of developing a new gadolinium-enhancing lesion was 62% lower in the newer-DMT group.

In terms of the safety of the newer DMTs, there were no surprises: The adverse-event profiles mirrored those that have been examined far more extensively in adults, according to Dr. Krysko.

The newer DMTs included oral agents as well as drugs given by intravenous infusion. The IV agents generally resulted in better disease control, compared with the oral agents, as one would expect, she said. The patient numbers were not sufficient to break down the results on an individual drug basis, however, even though this was a relatively large study.

Asked if these study results warranted a sweeping change in clinical practice – a move away from the conventional escalation treatment strategy in children in favor of upfront use of the newer, more effective DMTs – Dr. Krysko said that was tempting in light of a few recent studies in adults showing that even the first treatment can affect important long-term outcomes, including conversion to secondary progressive MS. However, she said she’d like to see additional studies in children that are focused on safety before making widespread changes in treatment strategy, especially because the pediatric MS network study did not include many very young children.

The study was sponsored by the Multiple Sclerosis Society. Dr. Kysko reported having no financial conflicts in regard to the study.

[email protected]

SOURCE: Krysko KM et al. ECTRIMS 2019, abstract 249.

STOCKHOLM – Radiologically isolated syndrome (RIS) converted to multiple sclerosis (MS) within 10 years of an initial abnormal MRI in 51% of patients in a large international cohort, Christine Lebrun-Frenay, MD, PhD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Bruce Jancin/MDedge News

She and her coinvestigators in the Radiologically Isolated Syndrome Consortium identified four significant risk factors for conversion. The likelihood of developing MS rose stepwise with the number of risk factors present at baseline such that patients possessing all four risk factors had an 87% conversion rate by 10 years.

The four significant risk factors that emerged from multivariate analysis were being age 37 years or younger at the time of the initial abnormal MRI, having spinal cord lesions on MRI, being cerebrospinal fluid positive for oligoclonal immunoglobulin bands and/or an elevated IgG index, and having infratentorial brain lesions on MRI.

Patients with none or one of the risk factors at baseline had a 29% conversion rate at 10 years. That risk climbed to 54% with two risk factors and 68% with any three, according to Dr. Lebrun-Frenay, head of the inflammatory neurologic disorders clinical research unit and MS Center at the University of Nice (France).

The new 10-year results expand upon the previously reported outcomes involving 5 years of prospective follow-up in the initial cohort of 451 RIS patients at participating MS centers in the United States, three European countries, and Turkey. At 5 years, 34% of subjects had converted to MS as defined by a first acute symptomatic clinical event involving CNS demyelination or 12 months of a progressive neurologic deficit (PLoS One. 2014 Mar 5;9[3]:e90509).

Of note, 17% of patients were treated off label with MS disease-modifying therapies, including natalizumab, injectables, or fingolimod, while they still had RIS, she noted.

RIS was defined on the basis of an incidentally identified CNS white-matter lesion meeting the 2009 Okuda criteria (Neurology. 2009 Mar 3;72[9]:800-5), which remain the only validated criteria for RIS.

Fourteen patients converted from RIS to primary progressive MS, indicating the existence of a previously unrecognized presymptomatic phase for this form of the disease.

The mounting conversions from RIS to MS over time suggest that RIS is part of the MS spectrum. In light of the RIS Consortium’s 10-year findings, Dr. Lebrun-Frenay and colleagues strongly recommended yearly monitoring of patients with RIS via a clinical visit including a neurologic examination and possibly a cognitive evaluation, as well as brain and spinal cord MRI scans.

Based on the observed conversion trajectory between 5 and 10 years, Dr. Lebrun-Frenay speculated that with further prospective follow-up eventually all of the RIS patients will develop MS. Despite this, she did not recommend prescribing disease-modifying therapies for these asymptomatic RIS patients. Dr. Lebrun-Frenay noted that there are two ongoing major randomized, phase 3, placebo-controlled clinical trials addressing this very question: the ARISE study of dimethyl fumarate in the United States, and the TERIS study of teriflunomide in Europe.

“It hasn’t been demonstrated yet that to give an active drug at this early stage is useful, so we have to wait a little bit for the results of these ongoing trials. I think we have to believe in evidence-based medicine. After all, 5 or 6 years ago we didn’t have any diagnostic criteria for RIS. We didn’t have any knowledge of this syndrome. Now we have to wait for maybe 2 years. It’s not too long to wait for the answer,” she said.

Dr. Lebrun-Frenay serves as a consultant to more than a half-dozen pharmaceutical companies but reported having no financial conflicts regarding the RIS Consortium study, which is being conducted without commercial support.
 

[email protected]

SOURCE: Lebrun-Frenay C et al. ECTRIMS 2019, Abstract 97.

STOCKHOLM – Radiologically isolated syndrome (RIS) converted to multiple sclerosis (MS) within 10 years of an initial abnormal MRI in 51% of patients in a large international cohort, Christine Lebrun-Frenay, MD, PhD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Bruce Jancin/MDedge News

She and her coinvestigators in the Radiologically Isolated Syndrome Consortium identified four significant risk factors for conversion. The likelihood of developing MS rose stepwise with the number of risk factors present at baseline such that patients possessing all four risk factors had an 87% conversion rate by 10 years.

The four significant risk factors that emerged from multivariate analysis were being age 37 years or younger at the time of the initial abnormal MRI, having spinal cord lesions on MRI, being cerebrospinal fluid positive for oligoclonal immunoglobulin bands and/or an elevated IgG index, and having infratentorial brain lesions on MRI.

Patients with none or one of the risk factors at baseline had a 29% conversion rate at 10 years. That risk climbed to 54% with two risk factors and 68% with any three, according to Dr. Lebrun-Frenay, head of the inflammatory neurologic disorders clinical research unit and MS Center at the University of Nice (France).

The new 10-year results expand upon the previously reported outcomes involving 5 years of prospective follow-up in the initial cohort of 451 RIS patients at participating MS centers in the United States, three European countries, and Turkey. At 5 years, 34% of subjects had converted to MS as defined by a first acute symptomatic clinical event involving CNS demyelination or 12 months of a progressive neurologic deficit (PLoS One. 2014 Mar 5;9[3]:e90509).

Of note, 17% of patients were treated off label with MS disease-modifying therapies, including natalizumab, injectables, or fingolimod, while they still had RIS, she noted.

RIS was defined on the basis of an incidentally identified CNS white-matter lesion meeting the 2009 Okuda criteria (Neurology. 2009 Mar 3;72[9]:800-5), which remain the only validated criteria for RIS.

Fourteen patients converted from RIS to primary progressive MS, indicating the existence of a previously unrecognized presymptomatic phase for this form of the disease.

The mounting conversions from RIS to MS over time suggest that RIS is part of the MS spectrum. In light of the RIS Consortium’s 10-year findings, Dr. Lebrun-Frenay and colleagues strongly recommended yearly monitoring of patients with RIS via a clinical visit including a neurologic examination and possibly a cognitive evaluation, as well as brain and spinal cord MRI scans.

Based on the observed conversion trajectory between 5 and 10 years, Dr. Lebrun-Frenay speculated that with further prospective follow-up eventually all of the RIS patients will develop MS. Despite this, she did not recommend prescribing disease-modifying therapies for these asymptomatic RIS patients. Dr. Lebrun-Frenay noted that there are two ongoing major randomized, phase 3, placebo-controlled clinical trials addressing this very question: the ARISE study of dimethyl fumarate in the United States, and the TERIS study of teriflunomide in Europe.

“It hasn’t been demonstrated yet that to give an active drug at this early stage is useful, so we have to wait a little bit for the results of these ongoing trials. I think we have to believe in evidence-based medicine. After all, 5 or 6 years ago we didn’t have any diagnostic criteria for RIS. We didn’t have any knowledge of this syndrome. Now we have to wait for maybe 2 years. It’s not too long to wait for the answer,” she said.

Dr. Lebrun-Frenay serves as a consultant to more than a half-dozen pharmaceutical companies but reported having no financial conflicts regarding the RIS Consortium study, which is being conducted without commercial support.
 

[email protected]

SOURCE: Lebrun-Frenay C et al. ECTRIMS 2019, Abstract 97.

STOCKHOLM – Radiologically isolated syndrome (RIS) converted to multiple sclerosis (MS) within 10 years of an initial abnormal MRI in 51% of patients in a large international cohort, Christine Lebrun-Frenay, MD, PhD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Bruce Jancin/MDedge News

She and her coinvestigators in the Radiologically Isolated Syndrome Consortium identified four significant risk factors for conversion. The likelihood of developing MS rose stepwise with the number of risk factors present at baseline such that patients possessing all four risk factors had an 87% conversion rate by 10 years.

The four significant risk factors that emerged from multivariate analysis were being age 37 years or younger at the time of the initial abnormal MRI, having spinal cord lesions on MRI, being cerebrospinal fluid positive for oligoclonal immunoglobulin bands and/or an elevated IgG index, and having infratentorial brain lesions on MRI.

Patients with none or one of the risk factors at baseline had a 29% conversion rate at 10 years. That risk climbed to 54% with two risk factors and 68% with any three, according to Dr. Lebrun-Frenay, head of the inflammatory neurologic disorders clinical research unit and MS Center at the University of Nice (France).

The new 10-year results expand upon the previously reported outcomes involving 5 years of prospective follow-up in the initial cohort of 451 RIS patients at participating MS centers in the United States, three European countries, and Turkey. At 5 years, 34% of subjects had converted to MS as defined by a first acute symptomatic clinical event involving CNS demyelination or 12 months of a progressive neurologic deficit (PLoS One. 2014 Mar 5;9[3]:e90509).

Of note, 17% of patients were treated off label with MS disease-modifying therapies, including natalizumab, injectables, or fingolimod, while they still had RIS, she noted.

RIS was defined on the basis of an incidentally identified CNS white-matter lesion meeting the 2009 Okuda criteria (Neurology. 2009 Mar 3;72[9]:800-5), which remain the only validated criteria for RIS.

Fourteen patients converted from RIS to primary progressive MS, indicating the existence of a previously unrecognized presymptomatic phase for this form of the disease.

The mounting conversions from RIS to MS over time suggest that RIS is part of the MS spectrum. In light of the RIS Consortium’s 10-year findings, Dr. Lebrun-Frenay and colleagues strongly recommended yearly monitoring of patients with RIS via a clinical visit including a neurologic examination and possibly a cognitive evaluation, as well as brain and spinal cord MRI scans.

Based on the observed conversion trajectory between 5 and 10 years, Dr. Lebrun-Frenay speculated that with further prospective follow-up eventually all of the RIS patients will develop MS. Despite this, she did not recommend prescribing disease-modifying therapies for these asymptomatic RIS patients. Dr. Lebrun-Frenay noted that there are two ongoing major randomized, phase 3, placebo-controlled clinical trials addressing this very question: the ARISE study of dimethyl fumarate in the United States, and the TERIS study of teriflunomide in Europe.

“It hasn’t been demonstrated yet that to give an active drug at this early stage is useful, so we have to wait a little bit for the results of these ongoing trials. I think we have to believe in evidence-based medicine. After all, 5 or 6 years ago we didn’t have any diagnostic criteria for RIS. We didn’t have any knowledge of this syndrome. Now we have to wait for maybe 2 years. It’s not too long to wait for the answer,” she said.

Dr. Lebrun-Frenay serves as a consultant to more than a half-dozen pharmaceutical companies but reported having no financial conflicts regarding the RIS Consortium study, which is being conducted without commercial support.
 

[email protected]

SOURCE: Lebrun-Frenay C et al. ECTRIMS 2019, Abstract 97.

STOCKHOLM – Pooled data from several national multiple sclerosis (MS) registries indicate that continuous exposure to disease-modifying therapy (DMT) for more than 10 years reduces the risk of confirmed disability progression (CDP), according to an investigation presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Using several confirmation points for Expanded Disability Status Scale (EDSS) progression (e.g., 12 months and 24 months), researchers detected a clear gradient of treatment effect. Identification of the most reliable outcome definitions will require further investigations, they said.

“The ultimate goal of MS treatment is the prevention of long-term disability accumulation,” said Giuseppe Lucisano, a biostatistician at the Center for Outcomes Research and Clinical Epidemiology in Pescara, Italy. “Continuous DMT exposure can impact long-term disability accumulation in MS, but it has not been definitively demonstrated yet.”

Registries and clinical databases provide the opportunity to collect longitudinal data for treated and untreated patients as a means of investigating questions such as this one, the researchers said. The Danish, Italian, and Swedish national MS registries, MSBase, and the Observatoire of MS (OFSEP) merged their data in the Big Multiple Sclerosis Data (BMSD) Network, which includes approximately 150,000 patients and more than 470,000 EDSS evaluations. The result is a large dataset suitable for long-term longitudinal studies.

[email protected]

SOURCE: Laffaldano P et al. ECTRIMS 2019. Abstract: 94.

STOCKHOLM – Pooled data from several national multiple sclerosis (MS) registries indicate that continuous exposure to disease-modifying therapy (DMT) for more than 10 years reduces the risk of confirmed disability progression (CDP), according to an investigation presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Using several confirmation points for Expanded Disability Status Scale (EDSS) progression (e.g., 12 months and 24 months), researchers detected a clear gradient of treatment effect. Identification of the most reliable outcome definitions will require further investigations, they said.

“The ultimate goal of MS treatment is the prevention of long-term disability accumulation,” said Giuseppe Lucisano, a biostatistician at the Center for Outcomes Research and Clinical Epidemiology in Pescara, Italy. “Continuous DMT exposure can impact long-term disability accumulation in MS, but it has not been definitively demonstrated yet.”

Registries and clinical databases provide the opportunity to collect longitudinal data for treated and untreated patients as a means of investigating questions such as this one, the researchers said. The Danish, Italian, and Swedish national MS registries, MSBase, and the Observatoire of MS (OFSEP) merged their data in the Big Multiple Sclerosis Data (BMSD) Network, which includes approximately 150,000 patients and more than 470,000 EDSS evaluations. The result is a large dataset suitable for long-term longitudinal studies.

[email protected]

SOURCE: Laffaldano P et al. ECTRIMS 2019. Abstract: 94.

STOCKHOLM – Pooled data from several national multiple sclerosis (MS) registries indicate that continuous exposure to disease-modifying therapy (DMT) for more than 10 years reduces the risk of confirmed disability progression (CDP), according to an investigation presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Using several confirmation points for Expanded Disability Status Scale (EDSS) progression (e.g., 12 months and 24 months), researchers detected a clear gradient of treatment effect. Identification of the most reliable outcome definitions will require further investigations, they said.

“The ultimate goal of MS treatment is the prevention of long-term disability accumulation,” said Giuseppe Lucisano, a biostatistician at the Center for Outcomes Research and Clinical Epidemiology in Pescara, Italy. “Continuous DMT exposure can impact long-term disability accumulation in MS, but it has not been definitively demonstrated yet.”

Registries and clinical databases provide the opportunity to collect longitudinal data for treated and untreated patients as a means of investigating questions such as this one, the researchers said. The Danish, Italian, and Swedish national MS registries, MSBase, and the Observatoire of MS (OFSEP) merged their data in the Big Multiple Sclerosis Data (BMSD) Network, which includes approximately 150,000 patients and more than 470,000 EDSS evaluations. The result is a large dataset suitable for long-term longitudinal studies.

[email protected]

SOURCE: Laffaldano P et al. ECTRIMS 2019. Abstract: 94.

Oral administration of vamorolone, a first-in-class investigational steroidal anti-inflammatory drug, may benefit patients with Duchenne muscular dystrophy (DMD), data from an open-label study suggest.

Jonathan Cohen/Binghamton University

Daily treatment with vamorolone at doses of 2.0 mg/kg per day and 6.0 mg/kg per day suggested possible efficacy in a 24-week study, researchers said. The exploratory study included 48 boys who had completed a phase 2a trial.

The treatment was safe and well tolerated, and patients who received 2.0 mg/kg per day had significantly improved muscle function, as assessed by time to stand, compared with natural history controls, according to the results, which were published in Neurology.

In addition, the novel drug may reduce “safety concerns typically seen with traditional glucocorticoids,” wrote Eric P. Hoffman, PhD, and coauthors. Dr. Hoffman is president and CEO of ReveraGen BioPharma in Rockville, Md., which is developing the drug, and associate dean for research in the school of pharmacy and pharmaceutical sciences at Binghamton (N.Y.) University.

In preclinical studies, vamorolone retained anti-inflammatory efficacy while reducing adverse effects, compared with prednisolone, in a manner that is “consistent with vamorolone blocking [nuclear factor-kappa beta]–associated proinflammatory signals as a ligand/receptor monomeric state instead of the traditional molecular models of ligand/receptor dimeric complexes,” the authors said.

[email protected]

SOURCE: Hoffman EP et al. Neurology. 2019 Aug 26. doi: 10.1212/WNL.0000000000008168.

Oral administration of vamorolone, a first-in-class investigational steroidal anti-inflammatory drug, may benefit patients with Duchenne muscular dystrophy (DMD), data from an open-label study suggest.

Jonathan Cohen/Binghamton University

Daily treatment with vamorolone at doses of 2.0 mg/kg per day and 6.0 mg/kg per day suggested possible efficacy in a 24-week study, researchers said. The exploratory study included 48 boys who had completed a phase 2a trial.

The treatment was safe and well tolerated, and patients who received 2.0 mg/kg per day had significantly improved muscle function, as assessed by time to stand, compared with natural history controls, according to the results, which were published in Neurology.

In addition, the novel drug may reduce “safety concerns typically seen with traditional glucocorticoids,” wrote Eric P. Hoffman, PhD, and coauthors. Dr. Hoffman is president and CEO of ReveraGen BioPharma in Rockville, Md., which is developing the drug, and associate dean for research in the school of pharmacy and pharmaceutical sciences at Binghamton (N.Y.) University.

In preclinical studies, vamorolone retained anti-inflammatory efficacy while reducing adverse effects, compared with prednisolone, in a manner that is “consistent with vamorolone blocking [nuclear factor-kappa beta]–associated proinflammatory signals as a ligand/receptor monomeric state instead of the traditional molecular models of ligand/receptor dimeric complexes,” the authors said.

[email protected]

SOURCE: Hoffman EP et al. Neurology. 2019 Aug 26. doi: 10.1212/WNL.0000000000008168.

Oral administration of vamorolone, a first-in-class investigational steroidal anti-inflammatory drug, may benefit patients with Duchenne muscular dystrophy (DMD), data from an open-label study suggest.

Jonathan Cohen/Binghamton University

Daily treatment with vamorolone at doses of 2.0 mg/kg per day and 6.0 mg/kg per day suggested possible efficacy in a 24-week study, researchers said. The exploratory study included 48 boys who had completed a phase 2a trial.

The treatment was safe and well tolerated, and patients who received 2.0 mg/kg per day had significantly improved muscle function, as assessed by time to stand, compared with natural history controls, according to the results, which were published in Neurology.

In addition, the novel drug may reduce “safety concerns typically seen with traditional glucocorticoids,” wrote Eric P. Hoffman, PhD, and coauthors. Dr. Hoffman is president and CEO of ReveraGen BioPharma in Rockville, Md., which is developing the drug, and associate dean for research in the school of pharmacy and pharmaceutical sciences at Binghamton (N.Y.) University.

In preclinical studies, vamorolone retained anti-inflammatory efficacy while reducing adverse effects, compared with prednisolone, in a manner that is “consistent with vamorolone blocking [nuclear factor-kappa beta]–associated proinflammatory signals as a ligand/receptor monomeric state instead of the traditional molecular models of ligand/receptor dimeric complexes,” the authors said.

[email protected]

SOURCE: Hoffman EP et al. Neurology. 2019 Aug 26. doi: 10.1212/WNL.0000000000008168.

A prosthetic leg that elicits the sensation of knee motion and the feeling of the sole of the foot touching the ground may improve walking performance and reduce phantom limb pain, according to a proof-of-concept study with two patients.

Huntstock/thinkstockphotos

With the bionic leg system, the patients performed better during clinically important tests indoors and outdoors, study author Stanisa Raspopovic, PhD, explained during a press briefing about the research. The findings were published in Nature Medicine.

The results indicate that the use of sensory feedback “could be common practice” in prosthetic devices in the future, he said. Dr. Raspopovic is a researcher at Swiss Federal Institute of Technology Zürich and a founder of SensArs Neuroprosthetics, which is based in Lausanne, Switzerland.

Neural prosthetics allow the nervous system and external devices to interact. These brain-machine interfaces may improve quality of life for patients with brain or spinal cord injuries, degenerative disease, or loss of limbs.

“Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users,” the study authors wrote. Users may also have high levels of mental and physical fatigue, and the lack of physiologic feedback from the extremity to the brain may contribute to the generation of phantom limb pain.

To evaluate whether neural sensory feedback restoration could address these issues, investigators conducted a study with two patients who had undergone transfemoral amputations as a result of traumatic events. The patients were implanted with four intraneural stimulation electrodes in the remaining tibial nerve. The prosthetic leg device included sensors to represent foot touch and pressure and knee joint angle. The sensors transmitted sensory signals to the nervous system through the stimulation electrodes in the tibial nerve.

When the patients walked outdoors over a path traced in the sand, “participants’ speeds were significantly higher when sensory feedback was provided,” the authors wrote. One participant walked 3.56 m/min faster, and the other walked 5.68 m/min faster.

The participants also rated their confidence in the prosthesis on a scale from 0 to 10. For patient 1, self-rated confidence improved from 4.85 to 7.71 with the device. Patient 2 reported a confidence level that climbed from 2.7 to 5.55.

When tested indoors, both patients reached a 0.5 km/hour higher speed on the treadmill when stimulation was provided and both had a lower mean rate of oxygen uptake during the sensory feedback trials, the study authors reported.

Levels of phantom limb pain also decreased significantly after 10-minute stimulation sessions, but not during control sessions.

Longer studies with more patients are required, and fully implantable devices without transcutaneous cables need to be developed, the authors wrote.

Grants from the European Research Council, European Commission, and Swiss National Science Foundation funded the research. Dr. Raspopovic and two coauthors hold shares of SensArs Neuroprosthetics, a start-up company dealing with the commercialization of neurocontrolled artificial limbs.

[email protected]

SOURCE: Petrini FM et al. Nat Med. 2019 Sep 9. doi: 10.1038/s41591-019-0567-3.

A prosthetic leg that elicits the sensation of knee motion and the feeling of the sole of the foot touching the ground may improve walking performance and reduce phantom limb pain, according to a proof-of-concept study with two patients.

Huntstock/thinkstockphotos

With the bionic leg system, the patients performed better during clinically important tests indoors and outdoors, study author Stanisa Raspopovic, PhD, explained during a press briefing about the research. The findings were published in Nature Medicine.

The results indicate that the use of sensory feedback “could be common practice” in prosthetic devices in the future, he said. Dr. Raspopovic is a researcher at Swiss Federal Institute of Technology Zürich and a founder of SensArs Neuroprosthetics, which is based in Lausanne, Switzerland.

Neural prosthetics allow the nervous system and external devices to interact. These brain-machine interfaces may improve quality of life for patients with brain or spinal cord injuries, degenerative disease, or loss of limbs.

“Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users,” the study authors wrote. Users may also have high levels of mental and physical fatigue, and the lack of physiologic feedback from the extremity to the brain may contribute to the generation of phantom limb pain.

To evaluate whether neural sensory feedback restoration could address these issues, investigators conducted a study with two patients who had undergone transfemoral amputations as a result of traumatic events. The patients were implanted with four intraneural stimulation electrodes in the remaining tibial nerve. The prosthetic leg device included sensors to represent foot touch and pressure and knee joint angle. The sensors transmitted sensory signals to the nervous system through the stimulation electrodes in the tibial nerve.

When the patients walked outdoors over a path traced in the sand, “participants’ speeds were significantly higher when sensory feedback was provided,” the authors wrote. One participant walked 3.56 m/min faster, and the other walked 5.68 m/min faster.

The participants also rated their confidence in the prosthesis on a scale from 0 to 10. For patient 1, self-rated confidence improved from 4.85 to 7.71 with the device. Patient 2 reported a confidence level that climbed from 2.7 to 5.55.

When tested indoors, both patients reached a 0.5 km/hour higher speed on the treadmill when stimulation was provided and both had a lower mean rate of oxygen uptake during the sensory feedback trials, the study authors reported.

Levels of phantom limb pain also decreased significantly after 10-minute stimulation sessions, but not during control sessions.

Longer studies with more patients are required, and fully implantable devices without transcutaneous cables need to be developed, the authors wrote.

Grants from the European Research Council, European Commission, and Swiss National Science Foundation funded the research. Dr. Raspopovic and two coauthors hold shares of SensArs Neuroprosthetics, a start-up company dealing with the commercialization of neurocontrolled artificial limbs.

[email protected]

SOURCE: Petrini FM et al. Nat Med. 2019 Sep 9. doi: 10.1038/s41591-019-0567-3.

A prosthetic leg that elicits the sensation of knee motion and the feeling of the sole of the foot touching the ground may improve walking performance and reduce phantom limb pain, according to a proof-of-concept study with two patients.

Huntstock/thinkstockphotos

With the bionic leg system, the patients performed better during clinically important tests indoors and outdoors, study author Stanisa Raspopovic, PhD, explained during a press briefing about the research. The findings were published in Nature Medicine.

The results indicate that the use of sensory feedback “could be common practice” in prosthetic devices in the future, he said. Dr. Raspopovic is a researcher at Swiss Federal Institute of Technology Zürich and a founder of SensArs Neuroprosthetics, which is based in Lausanne, Switzerland.

Neural prosthetics allow the nervous system and external devices to interact. These brain-machine interfaces may improve quality of life for patients with brain or spinal cord injuries, degenerative disease, or loss of limbs.

“Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users,” the study authors wrote. Users may also have high levels of mental and physical fatigue, and the lack of physiologic feedback from the extremity to the brain may contribute to the generation of phantom limb pain.

To evaluate whether neural sensory feedback restoration could address these issues, investigators conducted a study with two patients who had undergone transfemoral amputations as a result of traumatic events. The patients were implanted with four intraneural stimulation electrodes in the remaining tibial nerve. The prosthetic leg device included sensors to represent foot touch and pressure and knee joint angle. The sensors transmitted sensory signals to the nervous system through the stimulation electrodes in the tibial nerve.

When the patients walked outdoors over a path traced in the sand, “participants’ speeds were significantly higher when sensory feedback was provided,” the authors wrote. One participant walked 3.56 m/min faster, and the other walked 5.68 m/min faster.

The participants also rated their confidence in the prosthesis on a scale from 0 to 10. For patient 1, self-rated confidence improved from 4.85 to 7.71 with the device. Patient 2 reported a confidence level that climbed from 2.7 to 5.55.

When tested indoors, both patients reached a 0.5 km/hour higher speed on the treadmill when stimulation was provided and both had a lower mean rate of oxygen uptake during the sensory feedback trials, the study authors reported.

Levels of phantom limb pain also decreased significantly after 10-minute stimulation sessions, but not during control sessions.

Longer studies with more patients are required, and fully implantable devices without transcutaneous cables need to be developed, the authors wrote.

Grants from the European Research Council, European Commission, and Swiss National Science Foundation funded the research. Dr. Raspopovic and two coauthors hold shares of SensArs Neuroprosthetics, a start-up company dealing with the commercialization of neurocontrolled artificial limbs.

[email protected]

SOURCE: Petrini FM et al. Nat Med. 2019 Sep 9. doi: 10.1038/s41591-019-0567-3.