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Increasing sepsis survivorship creates new challenges
SAN ANTONIO – , results of a retrospective, single-center analysis suggest.
The number of sepsis survivors at risk for hospital readmission rose substantially in recent years, according to the analysis of 17,256 adult medical and surgical admissions to University of Pennsylvania Health System hospitals between July 1, 2010, and June 30, 2015. The journal Critical Care Medicine published these results online as Mark E. Mikkelsen, MD, was presenting them at the Critical Care Congress sponsored by the Society for Critical Care Medicine.
Over the time period that Dr. Mikkelsen and his colleagues analyzed, the proportion of sepsis hospitalizations more than doubled from 3.9% to 9.4%, while in-hospital mortality rates for sepsis hospitalizations fell from 24.1% to 14.8%. As a result, the proportion of discharged patients at risk for readmission increased from 2.7% to 7.8%, noted Dr. Mikkelsen, associate professor of medicine at the Hospital of the University Of Pennsylvania, Philadelphia.
Thirty-day hospital readmission rates modestly declined from 26.4% to 23.1% over that time period, driven by reduced readmissions among survivors of nonsevere and nonpneumonia sepsis, Dr. Mikkelsen said. This decline in overall sepsis patient readmissions was offset by an increase in emergency department treat-and-release visits. Such visits rose from 2.8% in 2010 to a peak of 5.4% in 2014, Dr. Mikkelsen explained. Generally, readmission rates for severe sepsis patients have not changed over time, he added.
“I anticipate that each and every hospital represented in this room will experience a similar phenomenon,” he said. “Therefore, high quality postdischarge care is in fact urgently needed,” he added. “It is warranted that there is an international spotlight on sepsis beginning in the hospital but now continuing thereafter into the phase of life after sepsis.”
These findings reflect “great sepsis survivorship” and suggest new challenges to address, said Timothy G. Buchman, MD, PhD, editor-in-chief of the Critical Care Medicine and past president of the Society for Critical Care Medicine.
“It’s really extraordinary to see that the efforts that have been made by the Surviving Sepsis campaign have paid off,” Dr. Buchman said in an interview. “Now we need to look much more carefully at both the readmission issues, as well as the consequences of long-term sepsis survivorship, not just on patients, but also on their families.”
Dr. Mikkelsen and a study coauthor received support for article research from the National Institutes of Health.
SOURCE: Meyer N et al. Crit Care Med. 2018 Mar. doi: 10.1097/CCM. 0000000000002872.
SAN ANTONIO – , results of a retrospective, single-center analysis suggest.
The number of sepsis survivors at risk for hospital readmission rose substantially in recent years, according to the analysis of 17,256 adult medical and surgical admissions to University of Pennsylvania Health System hospitals between July 1, 2010, and June 30, 2015. The journal Critical Care Medicine published these results online as Mark E. Mikkelsen, MD, was presenting them at the Critical Care Congress sponsored by the Society for Critical Care Medicine.
Over the time period that Dr. Mikkelsen and his colleagues analyzed, the proportion of sepsis hospitalizations more than doubled from 3.9% to 9.4%, while in-hospital mortality rates for sepsis hospitalizations fell from 24.1% to 14.8%. As a result, the proportion of discharged patients at risk for readmission increased from 2.7% to 7.8%, noted Dr. Mikkelsen, associate professor of medicine at the Hospital of the University Of Pennsylvania, Philadelphia.
Thirty-day hospital readmission rates modestly declined from 26.4% to 23.1% over that time period, driven by reduced readmissions among survivors of nonsevere and nonpneumonia sepsis, Dr. Mikkelsen said. This decline in overall sepsis patient readmissions was offset by an increase in emergency department treat-and-release visits. Such visits rose from 2.8% in 2010 to a peak of 5.4% in 2014, Dr. Mikkelsen explained. Generally, readmission rates for severe sepsis patients have not changed over time, he added.
“I anticipate that each and every hospital represented in this room will experience a similar phenomenon,” he said. “Therefore, high quality postdischarge care is in fact urgently needed,” he added. “It is warranted that there is an international spotlight on sepsis beginning in the hospital but now continuing thereafter into the phase of life after sepsis.”
These findings reflect “great sepsis survivorship” and suggest new challenges to address, said Timothy G. Buchman, MD, PhD, editor-in-chief of the Critical Care Medicine and past president of the Society for Critical Care Medicine.
“It’s really extraordinary to see that the efforts that have been made by the Surviving Sepsis campaign have paid off,” Dr. Buchman said in an interview. “Now we need to look much more carefully at both the readmission issues, as well as the consequences of long-term sepsis survivorship, not just on patients, but also on their families.”
Dr. Mikkelsen and a study coauthor received support for article research from the National Institutes of Health.
SOURCE: Meyer N et al. Crit Care Med. 2018 Mar. doi: 10.1097/CCM. 0000000000002872.
SAN ANTONIO – , results of a retrospective, single-center analysis suggest.
The number of sepsis survivors at risk for hospital readmission rose substantially in recent years, according to the analysis of 17,256 adult medical and surgical admissions to University of Pennsylvania Health System hospitals between July 1, 2010, and June 30, 2015. The journal Critical Care Medicine published these results online as Mark E. Mikkelsen, MD, was presenting them at the Critical Care Congress sponsored by the Society for Critical Care Medicine.
Over the time period that Dr. Mikkelsen and his colleagues analyzed, the proportion of sepsis hospitalizations more than doubled from 3.9% to 9.4%, while in-hospital mortality rates for sepsis hospitalizations fell from 24.1% to 14.8%. As a result, the proportion of discharged patients at risk for readmission increased from 2.7% to 7.8%, noted Dr. Mikkelsen, associate professor of medicine at the Hospital of the University Of Pennsylvania, Philadelphia.
Thirty-day hospital readmission rates modestly declined from 26.4% to 23.1% over that time period, driven by reduced readmissions among survivors of nonsevere and nonpneumonia sepsis, Dr. Mikkelsen said. This decline in overall sepsis patient readmissions was offset by an increase in emergency department treat-and-release visits. Such visits rose from 2.8% in 2010 to a peak of 5.4% in 2014, Dr. Mikkelsen explained. Generally, readmission rates for severe sepsis patients have not changed over time, he added.
“I anticipate that each and every hospital represented in this room will experience a similar phenomenon,” he said. “Therefore, high quality postdischarge care is in fact urgently needed,” he added. “It is warranted that there is an international spotlight on sepsis beginning in the hospital but now continuing thereafter into the phase of life after sepsis.”
These findings reflect “great sepsis survivorship” and suggest new challenges to address, said Timothy G. Buchman, MD, PhD, editor-in-chief of the Critical Care Medicine and past president of the Society for Critical Care Medicine.
“It’s really extraordinary to see that the efforts that have been made by the Surviving Sepsis campaign have paid off,” Dr. Buchman said in an interview. “Now we need to look much more carefully at both the readmission issues, as well as the consequences of long-term sepsis survivorship, not just on patients, but also on their families.”
Dr. Mikkelsen and a study coauthor received support for article research from the National Institutes of Health.
SOURCE: Meyer N et al. Crit Care Med. 2018 Mar. doi: 10.1097/CCM. 0000000000002872.
AT CCC47
Key clinical point: An analysis of one center’s sepsis cases revealed increases in sepsis survivors at risk for hospital readmission and returns of these patients to the hospital via the emergency department.
Major finding: The proportion of medical and surgical discharges at risk for hospital readmission after sepsis grew from 2.7% to 7.8%. The modest decline in 30-day readmission rates was offset by an increase in emergency department treat-and-release visits.
Data source: A retrospective, observational cohort study of more than 17,000 adult medical and surgical admissions in an academic health care system from 2010 to 2015.
Disclosures: The National Institutes of Health supported the work.
Source: Meyer N et al. Crit Care Med. 2018 Mar. doi: 10.1097/CCM.0000000000002872.
Levetiracetam May Be Superior to Phenobarbital for Infantile Epilepsy
Levetiracetam may be a superior initial treatment for infants with nonsyndromic epilepsy, according to a multicenter, prospective, observational study published online ahead of print February 12 in JAMA Pediatrics.
“Our findings suggest that levetiracetam has superior effectiveness, compared with phenobarbital, as initial monotherapy for nonsyndromic epilepsy in infants,” said Zachary Grinspan, MD, Director of the Pediatric Epilepsy Program at Cornell University, New York, and colleagues. “We estimate that for every 100 infants with epilepsy treated with levetiracetam instead of phenobarbital, 44 infants would be free from monotherapy failure instead of 16.” 
To evaluate the effectiveness of levetiracetam vs phenobarbital, the researchers conducted the Early Life Epilepsy Study, which included 155 children with nonsyndromic epilepsy. Patient information was obtained from medical records and collected from March 1, 2012, through April 30, 2015. All participants were observed during their first three years of life.
In all, 117 children were treated with levetiracetam, and 38 with phenobarbital. Children treated with levetiracetam were, on average, two months older at seizure onset than were those in the phenobarbital group (5.2 months vs 3.0 months). Infants treated with levetiracetam also tended to begin treatment further from the time of their first seizure and exhibited less developmental delay at the time of epilepsy diagnosis.
Freedom from monotherapy failure was more common in the levetiracetam group than the phenobarbital group (40.2% vs 15.8%).
Outcome information was missing for more infants treated with levetiracetam than those treated with phenobarbital, which could have influenced the analyses, said Dr. Grinspan. The genetic interactions that influence nonsyndromic epilepsy make the latter difficult to study.
Although this study provides information that could benefit patients with infantile epilepsy, more work must be done on the topic, said the investigators. “A prospective clinical trial is needed. Levetiracetam and phenobarbital are both commonly used for infantile-onset epilepsy, indicating community equipoise regarding their relative effectiveness,” they said. “However, the effect size in our analysis was surprisingly large (number needed to treat, 3.5), suggesting that a change in practice could meaningfully improve outcomes.”
—Ian Lacy
Suggested Reading
Grinspan ZM, Shellhaas RA, Coryell J, et al. Comparative effectiveness of levetiracetam vs phenobarbital for infantile epilepsy. JAMA Pediatr. 2018 Feb 12 [Epub ahead of print].
Levetiracetam may be a superior initial treatment for infants with nonsyndromic epilepsy, according to a multicenter, prospective, observational study published online ahead of print February 12 in JAMA Pediatrics.
“Our findings suggest that levetiracetam has superior effectiveness, compared with phenobarbital, as initial monotherapy for nonsyndromic epilepsy in infants,” said Zachary Grinspan, MD, Director of the Pediatric Epilepsy Program at Cornell University, New York, and colleagues. “We estimate that for every 100 infants with epilepsy treated with levetiracetam instead of phenobarbital, 44 infants would be free from monotherapy failure instead of 16.”
To evaluate the effectiveness of levetiracetam vs phenobarbital, the researchers conducted the Early Life Epilepsy Study, which included 155 children with nonsyndromic epilepsy. Patient information was obtained from medical records and collected from March 1, 2012, through April 30, 2015. All participants were observed during their first three years of life.
In all, 117 children were treated with levetiracetam, and 38 with phenobarbital. Children treated with levetiracetam were, on average, two months older at seizure onset than were those in the phenobarbital group (5.2 months vs 3.0 months). Infants treated with levetiracetam also tended to begin treatment further from the time of their first seizure and exhibited less developmental delay at the time of epilepsy diagnosis.
Freedom from monotherapy failure was more common in the levetiracetam group than the phenobarbital group (40.2% vs 15.8%).
Outcome information was missing for more infants treated with levetiracetam than those treated with phenobarbital, which could have influenced the analyses, said Dr. Grinspan. The genetic interactions that influence nonsyndromic epilepsy make the latter difficult to study.
Although this study provides information that could benefit patients with infantile epilepsy, more work must be done on the topic, said the investigators. “A prospective clinical trial is needed. Levetiracetam and phenobarbital are both commonly used for infantile-onset epilepsy, indicating community equipoise regarding their relative effectiveness,” they said. “However, the effect size in our analysis was surprisingly large (number needed to treat, 3.5), suggesting that a change in practice could meaningfully improve outcomes.”
—Ian Lacy
Suggested Reading
Grinspan ZM, Shellhaas RA, Coryell J, et al. Comparative effectiveness of levetiracetam vs phenobarbital for infantile epilepsy. JAMA Pediatr. 2018 Feb 12 [Epub ahead of print].
Levetiracetam may be a superior initial treatment for infants with nonsyndromic epilepsy, according to a multicenter, prospective, observational study published online ahead of print February 12 in JAMA Pediatrics.
“Our findings suggest that levetiracetam has superior effectiveness, compared with phenobarbital, as initial monotherapy for nonsyndromic epilepsy in infants,” said Zachary Grinspan, MD, Director of the Pediatric Epilepsy Program at Cornell University, New York, and colleagues. “We estimate that for every 100 infants with epilepsy treated with levetiracetam instead of phenobarbital, 44 infants would be free from monotherapy failure instead of 16.”
To evaluate the effectiveness of levetiracetam vs phenobarbital, the researchers conducted the Early Life Epilepsy Study, which included 155 children with nonsyndromic epilepsy. Patient information was obtained from medical records and collected from March 1, 2012, through April 30, 2015. All participants were observed during their first three years of life.
In all, 117 children were treated with levetiracetam, and 38 with phenobarbital. Children treated with levetiracetam were, on average, two months older at seizure onset than were those in the phenobarbital group (5.2 months vs 3.0 months). Infants treated with levetiracetam also tended to begin treatment further from the time of their first seizure and exhibited less developmental delay at the time of epilepsy diagnosis.
Freedom from monotherapy failure was more common in the levetiracetam group than the phenobarbital group (40.2% vs 15.8%).
Outcome information was missing for more infants treated with levetiracetam than those treated with phenobarbital, which could have influenced the analyses, said Dr. Grinspan. The genetic interactions that influence nonsyndromic epilepsy make the latter difficult to study.
Although this study provides information that could benefit patients with infantile epilepsy, more work must be done on the topic, said the investigators. “A prospective clinical trial is needed. Levetiracetam and phenobarbital are both commonly used for infantile-onset epilepsy, indicating community equipoise regarding their relative effectiveness,” they said. “However, the effect size in our analysis was surprisingly large (number needed to treat, 3.5), suggesting that a change in practice could meaningfully improve outcomes.”
—Ian Lacy
Suggested Reading
Grinspan ZM, Shellhaas RA, Coryell J, et al. Comparative effectiveness of levetiracetam vs phenobarbital for infantile epilepsy. JAMA Pediatr. 2018 Feb 12 [Epub ahead of print].
No Consensus Treatment for Neurosarcoidosis
NAPLES, FL—Although patients with symptomatic neurosarcoidosis account for approximately 5% to 15% of people with systemic sarcoidosis, making it a rare manifestation of an uncommon disorder, neurosarcoidosis is associated with substantial morbidity and with mortality rates ranging from about 1% to 7%. Steroids can be an effective treatment, but high doses over a long period of time are often required, relapse rates are relatively high, and a significant percentage of cases are refractory to first-line therapy. Additional therapies, including steroid-sparing immunosuppressive agents, show promise. Current evidence is based largely on small series of patients, however, and these treatments remain off-label, according to a presentation given at the 45th Annual Meeting of the Southern Clinical Neurological Society. 
In the absence of accepted standards, treatment mainly is informed by small series and anecdotal experiences, said Christopher Eckstein, MD, Assistant Professor of Neurology at the Duke University School of Medicine in Durham, North Carolina. “Nobody really knows exactly what to do,” he said.
A Higher Cutoff for Recurrence
To compensate for this uncertainty, as well as for the lack of robust data, Dr. Eckstein offered clinical treatment strategies based on his own experience and other anecdotal sources. Steroids play a large role in treatment. For acute treatment, corticosteroids are the main first-line therapies and typically are administered in high doses for a long time. “It is not uncommon for me to start patients with clear neurosarcoidosis on 80 mg to 100 mg of prednisone a day, keep them there for four weeks, and then taper down by 10 mg every two weeks until I get to 40 mg,” he said. “Then I take it down by 5 mg every two weeks till I get to about 10 mg. The reason I slow it down is because, once I get [the dosage] to about 40 mg or below it, that is where I tend to see, anecdotally at least, my sarcoid patients relapse.”
For patients with cardiac sarcoidosis who present to Duke, clinicians usually reduce the dosage to 25 mg before patients start to have recurrent symptoms, said Dr. Eckstein. Recurrent symptoms usually do not arise until the dosage goes below approximately 10 mg for patients with pulmonary sarcoidosis. Patients with neurosarcoidosis often require higher doses, however, said Dr. Eckstein. “Frequently, when I hit that 35-mg mark, I do another MRI, and we will see patients who either have recurrence of their symptoms or their enhancement has returned. It is not unusual for patients to be on steroids sometimes up to a year.”
Cases of refractory or recurrent neurosarcoidosis generally are treated with broad-spectrum immunosuppression. Several steroid-sparing agents and mechanisms are available, and their use in neurosarcoidosis is based on case series involving small numbers of patients. The original case series for methotrexate included eight patients, that for mycophenolate included three patients, that for azathioprine included less than 12, that for cyclosporine had 13, and that for TNF-alpha inhibitors such as infliximab and adalimumab included 17.
Dr. Eckstein will often start patients on one of these agents when he is weaning them from a steroid. “I usually do repeat MRIs when I get them around 35–40 mg, when I get them below 20 mg, and then when I get them off prednisone,” he said. “If we see recurrence, or their symptoms start to recur, and we see that they are refractory to steroids alone, we will often add these in.”
These agents are increasingly being added to first-line therapy for neurosarcoidosis, along with prednisone, said Dr. Eckstein. “But I find that enough [patients] are steroid-responsive and do not need things like infliximab that I do not necessarily start them right away.”
Choosing Among Oral Agents
Among the oral therapies, he uses methotrexate most. “I previously used a lot of mycophenolate; however, a recent retrospective comparison found that methotrexate’s recurrence level was much lower than [that for] mycophenolate,” said Dr. Eckstein.
Hydroxychloroquine, which works well in treating mucocutaneous forms of sarcoidosis, does not seem especially effective for neurosarcoidosis, said Dr. Eckstein. He tends not to use cyclosporine often, considering that better tolerated therapies are available. For certain patients, cyclophosphamide is the only therapy that will control neurosarcoidosis, said Dr. Eckstein. These patients tend to be exceptionally refractory. “But generally with cyclophosphamide—with high enough doses for long enough—you can usually suppress it,” he said.
Adalimumab has been assessed mostly as a treatment for myelopathies. Studies suggest it to be effective and easy to tolerate.
Steroid-Sparing Agents Can Be Effective
The steroid-sparing agent that Dr. Eckstein currently uses the most is infliximab, which is administered IV. The patients tend to tolerate it well and have good outcomes. Dr. Eckstein usually starts treatment at the lowest dose he thinks will be efficacious. “Most neurologists have not used a lot of infliximab, but they send people to rheumatology for it,” he said. “I start at 5 mg/kg, I do an induction at day one, day 14, and then four weeks later, followed by maintenance dosing every eight weeks.”
For most of his patients, this regimen is sufficient, although some patients require doses of 8 mg/kg, and others need an infusion at that level every four to six weeks. These regimens are often effective. While such patients are usually on concurrent prednisone, a recent trend is to use concurrent methotrexate to prevent reactions to infliximab. A few patients who receive infliximab plus methotrexate tend to tolerate the combination fairly well, said Dr. Eckstein.
Researchers have studied one nonpharmacologic treatment for neurosarcoidosis: radiotherapy. Dr. Eckstein cited recent case reports that examined low-dose, whole-brain radiation in refractory cases. “This is not something I have any hands-on experience with,” he said. “Most of my patients have responded to one of the other steroid-sparing agents [listed] when they’re refractory. But this is something that may be looked at more in the next several years. If there are people who have a very focal kind of encephalitic nodules, they can [undergo] fractional or focal radiotherapy.”
—Fred Balzac
Suggested Reading
Fritz D, van de Beek D, Brouwer MC. Clinical features, treatment and outcome in neurosarcoidosis: systematic review and meta-analysis. BMC Neurol. 2016;16(1):220-227.
Gelfand JM, Bradshaw MJ, Stern BJ, et al. Infliximab for the treatment of CNS sarcoidosis: a multi-institutional series. Neurology. 2017;89(20):2092-2100.
Ibitoye RT, Wilkins A, Scolding NJ. Neurosarcoidosis: a clinical approach to diagnosis and management. J Neurol. 2017;264(5):1023-1028.
Saidha S, Sotirchos ES, Eckstein C. Etiology of sarcoidosis: does infection play a role? Yale J Biol Med. 2012;85(1):133-141.
Tana C, Wegener S, Borys E, et al. Challenges in the diagnosis and treatment of neurosarcoidosis. Ann Med. 2015;47(7):576-591.
Ungprasert P, Matteson EL. Neurosarcoidosis. Rheum Dis Clin North Am. 2017;43(4):593-606.
Ungprasert P, Crowson CS, Matteson EL. Characteristics and long-term outcome of neurosarcoidosis: a population-based study from 1976-2013. Neuroepidemiology. 2017;48(3-4):87-94.
NAPLES, FL—Although patients with symptomatic neurosarcoidosis account for approximately 5% to 15% of people with systemic sarcoidosis, making it a rare manifestation of an uncommon disorder, neurosarcoidosis is associated with substantial morbidity and with mortality rates ranging from about 1% to 7%. Steroids can be an effective treatment, but high doses over a long period of time are often required, relapse rates are relatively high, and a significant percentage of cases are refractory to first-line therapy. Additional therapies, including steroid-sparing immunosuppressive agents, show promise. Current evidence is based largely on small series of patients, however, and these treatments remain off-label, according to a presentation given at the 45th Annual Meeting of the Southern Clinical Neurological Society.
In the absence of accepted standards, treatment mainly is informed by small series and anecdotal experiences, said Christopher Eckstein, MD, Assistant Professor of Neurology at the Duke University School of Medicine in Durham, North Carolina. “Nobody really knows exactly what to do,” he said.
A Higher Cutoff for Recurrence
To compensate for this uncertainty, as well as for the lack of robust data, Dr. Eckstein offered clinical treatment strategies based on his own experience and other anecdotal sources. Steroids play a large role in treatment. For acute treatment, corticosteroids are the main first-line therapies and typically are administered in high doses for a long time. “It is not uncommon for me to start patients with clear neurosarcoidosis on 80 mg to 100 mg of prednisone a day, keep them there for four weeks, and then taper down by 10 mg every two weeks until I get to 40 mg,” he said. “Then I take it down by 5 mg every two weeks till I get to about 10 mg. The reason I slow it down is because, once I get [the dosage] to about 40 mg or below it, that is where I tend to see, anecdotally at least, my sarcoid patients relapse.”
For patients with cardiac sarcoidosis who present to Duke, clinicians usually reduce the dosage to 25 mg before patients start to have recurrent symptoms, said Dr. Eckstein. Recurrent symptoms usually do not arise until the dosage goes below approximately 10 mg for patients with pulmonary sarcoidosis. Patients with neurosarcoidosis often require higher doses, however, said Dr. Eckstein. “Frequently, when I hit that 35-mg mark, I do another MRI, and we will see patients who either have recurrence of their symptoms or their enhancement has returned. It is not unusual for patients to be on steroids sometimes up to a year.”
Cases of refractory or recurrent neurosarcoidosis generally are treated with broad-spectrum immunosuppression. Several steroid-sparing agents and mechanisms are available, and their use in neurosarcoidosis is based on case series involving small numbers of patients. The original case series for methotrexate included eight patients, that for mycophenolate included three patients, that for azathioprine included less than 12, that for cyclosporine had 13, and that for TNF-alpha inhibitors such as infliximab and adalimumab included 17.
Dr. Eckstein will often start patients on one of these agents when he is weaning them from a steroid. “I usually do repeat MRIs when I get them around 35–40 mg, when I get them below 20 mg, and then when I get them off prednisone,” he said. “If we see recurrence, or their symptoms start to recur, and we see that they are refractory to steroids alone, we will often add these in.”
These agents are increasingly being added to first-line therapy for neurosarcoidosis, along with prednisone, said Dr. Eckstein. “But I find that enough [patients] are steroid-responsive and do not need things like infliximab that I do not necessarily start them right away.”
Choosing Among Oral Agents
Among the oral therapies, he uses methotrexate most. “I previously used a lot of mycophenolate; however, a recent retrospective comparison found that methotrexate’s recurrence level was much lower than [that for] mycophenolate,” said Dr. Eckstein.
Hydroxychloroquine, which works well in treating mucocutaneous forms of sarcoidosis, does not seem especially effective for neurosarcoidosis, said Dr. Eckstein. He tends not to use cyclosporine often, considering that better tolerated therapies are available. For certain patients, cyclophosphamide is the only therapy that will control neurosarcoidosis, said Dr. Eckstein. These patients tend to be exceptionally refractory. “But generally with cyclophosphamide—with high enough doses for long enough—you can usually suppress it,” he said.
Adalimumab has been assessed mostly as a treatment for myelopathies. Studies suggest it to be effective and easy to tolerate.
Steroid-Sparing Agents Can Be Effective
The steroid-sparing agent that Dr. Eckstein currently uses the most is infliximab, which is administered IV. The patients tend to tolerate it well and have good outcomes. Dr. Eckstein usually starts treatment at the lowest dose he thinks will be efficacious. “Most neurologists have not used a lot of infliximab, but they send people to rheumatology for it,” he said. “I start at 5 mg/kg, I do an induction at day one, day 14, and then four weeks later, followed by maintenance dosing every eight weeks.”
For most of his patients, this regimen is sufficient, although some patients require doses of 8 mg/kg, and others need an infusion at that level every four to six weeks. These regimens are often effective. While such patients are usually on concurrent prednisone, a recent trend is to use concurrent methotrexate to prevent reactions to infliximab. A few patients who receive infliximab plus methotrexate tend to tolerate the combination fairly well, said Dr. Eckstein.
Researchers have studied one nonpharmacologic treatment for neurosarcoidosis: radiotherapy. Dr. Eckstein cited recent case reports that examined low-dose, whole-brain radiation in refractory cases. “This is not something I have any hands-on experience with,” he said. “Most of my patients have responded to one of the other steroid-sparing agents [listed] when they’re refractory. But this is something that may be looked at more in the next several years. If there are people who have a very focal kind of encephalitic nodules, they can [undergo] fractional or focal radiotherapy.”
—Fred Balzac
Suggested Reading
Fritz D, van de Beek D, Brouwer MC. Clinical features, treatment and outcome in neurosarcoidosis: systematic review and meta-analysis. BMC Neurol. 2016;16(1):220-227.
Gelfand JM, Bradshaw MJ, Stern BJ, et al. Infliximab for the treatment of CNS sarcoidosis: a multi-institutional series. Neurology. 2017;89(20):2092-2100.
Ibitoye RT, Wilkins A, Scolding NJ. Neurosarcoidosis: a clinical approach to diagnosis and management. J Neurol. 2017;264(5):1023-1028.
Saidha S, Sotirchos ES, Eckstein C. Etiology of sarcoidosis: does infection play a role? Yale J Biol Med. 2012;85(1):133-141.
Tana C, Wegener S, Borys E, et al. Challenges in the diagnosis and treatment of neurosarcoidosis. Ann Med. 2015;47(7):576-591.
Ungprasert P, Matteson EL. Neurosarcoidosis. Rheum Dis Clin North Am. 2017;43(4):593-606.
Ungprasert P, Crowson CS, Matteson EL. Characteristics and long-term outcome of neurosarcoidosis: a population-based study from 1976-2013. Neuroepidemiology. 2017;48(3-4):87-94.
NAPLES, FL—Although patients with symptomatic neurosarcoidosis account for approximately 5% to 15% of people with systemic sarcoidosis, making it a rare manifestation of an uncommon disorder, neurosarcoidosis is associated with substantial morbidity and with mortality rates ranging from about 1% to 7%. Steroids can be an effective treatment, but high doses over a long period of time are often required, relapse rates are relatively high, and a significant percentage of cases are refractory to first-line therapy. Additional therapies, including steroid-sparing immunosuppressive agents, show promise. Current evidence is based largely on small series of patients, however, and these treatments remain off-label, according to a presentation given at the 45th Annual Meeting of the Southern Clinical Neurological Society.
In the absence of accepted standards, treatment mainly is informed by small series and anecdotal experiences, said Christopher Eckstein, MD, Assistant Professor of Neurology at the Duke University School of Medicine in Durham, North Carolina. “Nobody really knows exactly what to do,” he said.
A Higher Cutoff for Recurrence
To compensate for this uncertainty, as well as for the lack of robust data, Dr. Eckstein offered clinical treatment strategies based on his own experience and other anecdotal sources. Steroids play a large role in treatment. For acute treatment, corticosteroids are the main first-line therapies and typically are administered in high doses for a long time. “It is not uncommon for me to start patients with clear neurosarcoidosis on 80 mg to 100 mg of prednisone a day, keep them there for four weeks, and then taper down by 10 mg every two weeks until I get to 40 mg,” he said. “Then I take it down by 5 mg every two weeks till I get to about 10 mg. The reason I slow it down is because, once I get [the dosage] to about 40 mg or below it, that is where I tend to see, anecdotally at least, my sarcoid patients relapse.”
For patients with cardiac sarcoidosis who present to Duke, clinicians usually reduce the dosage to 25 mg before patients start to have recurrent symptoms, said Dr. Eckstein. Recurrent symptoms usually do not arise until the dosage goes below approximately 10 mg for patients with pulmonary sarcoidosis. Patients with neurosarcoidosis often require higher doses, however, said Dr. Eckstein. “Frequently, when I hit that 35-mg mark, I do another MRI, and we will see patients who either have recurrence of their symptoms or their enhancement has returned. It is not unusual for patients to be on steroids sometimes up to a year.”
Cases of refractory or recurrent neurosarcoidosis generally are treated with broad-spectrum immunosuppression. Several steroid-sparing agents and mechanisms are available, and their use in neurosarcoidosis is based on case series involving small numbers of patients. The original case series for methotrexate included eight patients, that for mycophenolate included three patients, that for azathioprine included less than 12, that for cyclosporine had 13, and that for TNF-alpha inhibitors such as infliximab and adalimumab included 17.
Dr. Eckstein will often start patients on one of these agents when he is weaning them from a steroid. “I usually do repeat MRIs when I get them around 35–40 mg, when I get them below 20 mg, and then when I get them off prednisone,” he said. “If we see recurrence, or their symptoms start to recur, and we see that they are refractory to steroids alone, we will often add these in.”
These agents are increasingly being added to first-line therapy for neurosarcoidosis, along with prednisone, said Dr. Eckstein. “But I find that enough [patients] are steroid-responsive and do not need things like infliximab that I do not necessarily start them right away.”
Choosing Among Oral Agents
Among the oral therapies, he uses methotrexate most. “I previously used a lot of mycophenolate; however, a recent retrospective comparison found that methotrexate’s recurrence level was much lower than [that for] mycophenolate,” said Dr. Eckstein.
Hydroxychloroquine, which works well in treating mucocutaneous forms of sarcoidosis, does not seem especially effective for neurosarcoidosis, said Dr. Eckstein. He tends not to use cyclosporine often, considering that better tolerated therapies are available. For certain patients, cyclophosphamide is the only therapy that will control neurosarcoidosis, said Dr. Eckstein. These patients tend to be exceptionally refractory. “But generally with cyclophosphamide—with high enough doses for long enough—you can usually suppress it,” he said.
Adalimumab has been assessed mostly as a treatment for myelopathies. Studies suggest it to be effective and easy to tolerate.
Steroid-Sparing Agents Can Be Effective
The steroid-sparing agent that Dr. Eckstein currently uses the most is infliximab, which is administered IV. The patients tend to tolerate it well and have good outcomes. Dr. Eckstein usually starts treatment at the lowest dose he thinks will be efficacious. “Most neurologists have not used a lot of infliximab, but they send people to rheumatology for it,” he said. “I start at 5 mg/kg, I do an induction at day one, day 14, and then four weeks later, followed by maintenance dosing every eight weeks.”
For most of his patients, this regimen is sufficient, although some patients require doses of 8 mg/kg, and others need an infusion at that level every four to six weeks. These regimens are often effective. While such patients are usually on concurrent prednisone, a recent trend is to use concurrent methotrexate to prevent reactions to infliximab. A few patients who receive infliximab plus methotrexate tend to tolerate the combination fairly well, said Dr. Eckstein.
Researchers have studied one nonpharmacologic treatment for neurosarcoidosis: radiotherapy. Dr. Eckstein cited recent case reports that examined low-dose, whole-brain radiation in refractory cases. “This is not something I have any hands-on experience with,” he said. “Most of my patients have responded to one of the other steroid-sparing agents [listed] when they’re refractory. But this is something that may be looked at more in the next several years. If there are people who have a very focal kind of encephalitic nodules, they can [undergo] fractional or focal radiotherapy.”
—Fred Balzac
Suggested Reading
Fritz D, van de Beek D, Brouwer MC. Clinical features, treatment and outcome in neurosarcoidosis: systematic review and meta-analysis. BMC Neurol. 2016;16(1):220-227.
Gelfand JM, Bradshaw MJ, Stern BJ, et al. Infliximab for the treatment of CNS sarcoidosis: a multi-institutional series. Neurology. 2017;89(20):2092-2100.
Ibitoye RT, Wilkins A, Scolding NJ. Neurosarcoidosis: a clinical approach to diagnosis and management. J Neurol. 2017;264(5):1023-1028.
Saidha S, Sotirchos ES, Eckstein C. Etiology of sarcoidosis: does infection play a role? Yale J Biol Med. 2012;85(1):133-141.
Tana C, Wegener S, Borys E, et al. Challenges in the diagnosis and treatment of neurosarcoidosis. Ann Med. 2015;47(7):576-591.
Ungprasert P, Matteson EL. Neurosarcoidosis. Rheum Dis Clin North Am. 2017;43(4):593-606.
Ungprasert P, Crowson CS, Matteson EL. Characteristics and long-term outcome of neurosarcoidosis: a population-based study from 1976-2013. Neuroepidemiology. 2017;48(3-4):87-94.
Conference News Roundup—American Association for the Advancement of Science
Stretchable Electronics Could Aid Stroke Recovery Treatment
A device designed to be worn on the throat could aid stroke rehabilitation, researchers said.
John A. Rogers, PhD, Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering, and Neurological Surgery at Northwestern University in Evanston, Illinois, developed the device in partnership with Shirley Ryan AbilityLab, a research hospital in Chicago. The sensor is the latest in Dr. Rogers’s portfolio of stretchable electronics that are appropriate for use in advanced medical care and portable enough to be worn outside the hospital and during exercise.
Dr. Rogers’s sensors stick directly to the skin, moving with the body and providing measurements, including heart function, muscle activity, and quality of sleep.
“Stretchable electronics allow us to see what is going on inside patients’ bodies at a level traditional wearables simply cannot achieve,” said Dr. Rogers. “The key is to make them as integrated as possible with the human body.”
The new bandage-like throat sensor measures patients’ swallowing ability and patterns of speech. The sensors aid in the diagnosis and treatment of aphasia.
The tools that speech-language pathologists have traditionally used to monitor patients’ speech function, such as microphones, cannot distinguish between patients’ voices and ambient noise.
“Our sensors solve that problem by measuring vibrations of the vocal cords,” Dr. Rogers said. “But they only work when worn directly on the throat, which is a sensitive area of the skin. We developed novel materials for this sensor that bend and stretch with the body, minimizing discomfort to patients.”
Shirley Ryan AbilityLab uses the throat sensor in conjunction with electronic biosensors, also developed in Dr. Rogers’s laboratory, on the legs, arms, and chest to monitor stroke patients’ recovery progress. The intermodal system of sensors streams data wirelessly to clinicians’ phones and computers, providing a quantitative picture of patients’ advanced physical and physiologic responses in real time.“One of the biggest problems we face with stroke patients is that their gains tend to drop off when they leave the hospital,” said Arun Jayaraman, PhD, research scientist at the Shirley Ryan AbilityLab. “With the home monitoring enabled by these sensors, we can intervene at the right time, which could lead to better, faster recoveries for patients.”
Because the sensors are wireless, they eliminate barriers posed by traditional health monitoring devices in clinical settings. Patients can wear them after they leave the hospital, allowing doctors to understand how their patients are functioning in the real world.
“Talking with friends and family at home is a completely different dimension from what we do in therapy,” said Leora Cherney, PhD, research scientist at the Shirley Ryan AbilityLab. “Having a detailed understanding of patients’ communication habits outside of the clinic helps us develop better strategies with our patients to improve their speaking skills and speed up their recovery process.”
Data from the sensors will be presented in a dashboard that is easy for clinicians and patients to understand. It will send alerts when patients are underperforming on a certain metric and allow them to set and track progress toward their goals.
Inhibiting an Enzyme May Aid Memory Creation
Aging or impaired brains can once again form lasting memories if an enzyme that impedes the function of a key gene too strongly is inhibited, according to neurobiologists at the University of California, Irvine.
“What we have discovered is that if we free up that DNA again, now the aging brain can form long-term memories normally,” said senior author Marcelo Wood, PhD, Francisco J. Ayala Chair in Neurobiology and Behavior at the university. “To form a long-term memory, you have to turn specific genes on. In most young brains, that happens easily, but as we get older and our brains get older, we have trouble with that.”
That is because the six feet of DNA spooled into every cell in our bodies has a harder time releasing itself as needed, he explained. Like many body parts, “it is no longer as flexible as it used to be,” said Dr. Wood. The stiffness in this case is due to a molecular brake pad called histone deacetylase 3 (HDAC3), that has become “overeager” in the aged brain and is compacting the material too hard, blocking the release of a gene called Period1, said Dr. Wood. Removing HDAC3 restores flexibility and allows internal cell machinery to access Period1 to begin forming new memories.
Researchers had previously theorized that the loss of transcription and encoding functions in older brains resulted from deteriorating core circadian clocks. But Dr. Wood and his team found that the ability to create lasting memories was linked to a different process—the enzyme blocking the release of Period1—in the hippocampus.
“New drugs targeting HDAC3 could provide an exciting avenue to allow older people to improve memory formation,” said Dr. Wood.
Unaffected Hemisphere Assumes Language Function After Perinatal Stroke
Babies sometimes have stroke around the time of birth. Birth is hard on the brain, as is the change in blood circulation from the mother to the neonate. At least one in 4,000 babies have stroke shortly before, during, or after birth.
But a stroke in a baby, even a big one, does not have the same lasting impact as a stroke in an adult. A study led by investigators at Georgetown University Medical Center in Washington, DC, found that a decade or two after a perinatal stroke damaged the left language side of the brain, affected teenagers and young adults used the right sides of their brains for language.The findings demonstrate how plastic brain function is in infants, said Elissa L. Newport, PhD, Professor of Neurology at Georgetown University School of Medicine, and Director of the Center for Brain Plasticity and Recovery at Georgetown University and MedStar National Rehabilitation Network.Her study found that the 12 individuals studied, aged 12 to 25, who had a left-brain perinatal stroke all used the right side of their brains for language. “Their language is good—normal,” she said.
The only signs of prior damage to their brains are that some participants limp, and many have learned to make their left hands dominant because their right hands had impaired function after stroke. They also have executive function impairments—slightly slower neural processing, for example—that are common in individuals with brain injuries. But basic cognitive functions, like language comprehension and production, are excellent, said Dr. Newport.
Furthermore, imaging studies revealed that language in these participants is based entirely in the right hemisphere, in the region opposite to the normal language areas in the left hemisphere. This result had been recorded in previous research, but earlier findings were inconsistent, perhaps because of the heterogeneity of the types of brain injuries included in those studies, said Dr. Newport. Her research, which was carefully controlled in terms of the types and areas of injury included, suggests that while “these young brains were plastic, meaning they could relocate language to a healthy area, it does not mean that new areas can be located willy-nilly on the right side.
“We believe there are important constraints on where functions can be relocated,” she continued. “There are specific regions that take over when part of the brain is injured, depending on the particular function. Each function, like language or spatial skills, has a particular region that can take over if its primary brain area is injured. This is an important discovery that may have implications in the rehabilitation of adult stroke survivors.”
This finding is consistent with the behavior of young brains, said Dr. Newport. “Imaging shows that children up to about age 4 can process language in both sides of their brains, and then the functions split up: the left side processes sentences, and the right processes emotion in language.”
Dr. Newport and her colleagues are extending their study of brain function after a perinatal stroke to a larger group of participants. They are examining stroke in the left and right hemispheres and also whether brain functions other than language are relocated and where. Her group is also collaborating on studies that may reveal the molecular basis of plasticity in young brains. This information might help promote plasticity in adults with stroke or brain injury.
Why Do We Sleep?
Evidence supports the synaptic homeostasis hypothesis about the function of sleep, said researchers. The debate about sleep’s function has continued for a generation and arose following observations that people and animals sicken and die if they are deprived of sleep.
Chiara Cirelli, MD, PhD, and Giulio Tononi, MD, PhD, psychiatrists at the Center for Sleep and Consciousness in Madison, Wisconsin, proposed the synaptic homeostasis hypothesis in 2003. This hypothesis holds that sleep is the price we pay for brains that are plastic and able to keep learning new things. They subsequently undertook a four-year research effort that could show direct evidence for their theory. The result was published in February 2017 in Science and offered direct visual proof of the hypothesis.
Striking electron-microscope pictures from inside the brains of mice suggest what happens in our own brains every day. Our synapses grow strong and large during the stimulation of daytime, then shrink by nearly 20% while we sleep, thus creating room for more growth and learning the next day.
A large team of researchers sectioned the brains of mice and used a scanning electron microscope to photograph, reconstruct, and analyze two areas of cerebral cortex. They were able to reconstruct 6,920 synapses and measure their size.
The team remained blinded about whether they were analyzing the brain cells of a well-rested mouse or one that had been awake. When they finally correlated the measurements with the amount of sleep the mice had had during the six to eight hours before the image was taken, they found that a few hours of sleep led on average to an 18% decrease in the size of the synapses. These changes occurred in both areas of the cerebral cortex and were proportional to the size of the synapses.
Dr. Cirelli’s laboratory is now looking at new brain areas, and at the brains of young mice, to understand the role that sleep plays in brain development.
Statistics and Neuroscience Can Improve Anesthesiology
Anesthesia is believed to act on the brain, but the standard protocol among anesthesiologists for monitoring and dosing patients during surgery is to rely on indirect signs of arousal, like movement and changes in heart rate and blood pressure. Research in brain science and statistical modeling has allowed Emery N. Brown, MD, PhD, an anesthetist at Massachusetts General Hospital in Boston, to safely give patients less anesthesia, which can be beneficial.
Dr. Brown has developed a theoretical (ie, neuroscientific) and analytical (ie, statistical) understanding of EEG brain wave measurements of patients under general anesthesia. Anesthesia’s effects in the brain produce specific patterns of brain waves, and monitoring them via EEG data can improve care.
“We should use neuroscience and neuroscience paradigms to try to understand what is happening in the brain under general anesthesia,” said Dr. Brown. “It is a neurophysiologic process that affects the brain and CNS, so how can it be that what is being developed in the neuroscience field is not being brought to bear on the question of the brain under anesthesia?”
In numerous papers over more than a decade, Dr. Brown has examined how various anesthesia drugs such as propofol, dexmedetomidine, and sevoflurane interact with various neuronal receptors, affecting circuits in different regions of the brain. Those neurophysiologic effects ultimately give rise to a state of unconsciousness—essentially a reversible coma—characterized by powerful, low-frequency brain waves that overwhelm the normal rhythms that synchronize brain functions such as sensory perception, higher cognition, or motor control.
Understanding anesthesia to this degree allows for practical insights. In a study published in October 2016 in Proceedings of the National Academy of Sciences, for example, Dr. Brown and colleagues showed how stimulating dopamine-producing neurons in the ventral tegmental area of the brain could wake mice up from general anesthesia. The study suggests a way that human patients could be awakened as well, which could lessen side effects, recover normal brain function more rapidly, and help patients move more quickly out of the operating room and into recovery.
In parallel with illuminating the neuroscience of general anesthesia, Dr. Brown has developed statistical methods to analyze EEG measurements in a way that anesthesiologists can apply to patients. Dr. Brown has shown that EEG readings of level of unconsciousness vary in characteristic ways based on the drug, its dose, and the patient’s age.
“The deciphering of how these drugs are acting in the brain turns out to be an important signal-processing question,” said Dr. Brown. “The drugs work by producing oscillations, these oscillations are readily visible in the EEG and change systematically with drug dose, class, and age.”
During every surgery, Dr. Brown uses real-time EEG readings to keep a patient adequately dosed without giving too much anesthetic. While treating an 81-year-old patient with cancer, Dr. Brown was able to administer about one-third of the dose considered necessary. This dose reduction can be especially important for older patients. “We already know you do not have to give older people as much, but it turns out it can be even less,” said Dr. Brown.
Older patients are especially susceptible to problematic side effects when they wake up, including delirium or postoperative cognitive dysfunction. Neuroscientifically informed ways to prevent giving too much anesthesia can help prevent such problems, said Dr. Brown.
As more anesthesiologists acquire knowledge and EEG equipment, the field can move to a model where doctors have a direct view of the patient’s brain when monitoring and maintaining their consciousness during surgery, said Dr. Brown.
Stretchable Electronics Could Aid Stroke Recovery Treatment
A device designed to be worn on the throat could aid stroke rehabilitation, researchers said.
John A. Rogers, PhD, Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering, and Neurological Surgery at Northwestern University in Evanston, Illinois, developed the device in partnership with Shirley Ryan AbilityLab, a research hospital in Chicago. The sensor is the latest in Dr. Rogers’s portfolio of stretchable electronics that are appropriate for use in advanced medical care and portable enough to be worn outside the hospital and during exercise.
Dr. Rogers’s sensors stick directly to the skin, moving with the body and providing measurements, including heart function, muscle activity, and quality of sleep.
“Stretchable electronics allow us to see what is going on inside patients’ bodies at a level traditional wearables simply cannot achieve,” said Dr. Rogers. “The key is to make them as integrated as possible with the human body.”
The new bandage-like throat sensor measures patients’ swallowing ability and patterns of speech. The sensors aid in the diagnosis and treatment of aphasia.
The tools that speech-language pathologists have traditionally used to monitor patients’ speech function, such as microphones, cannot distinguish between patients’ voices and ambient noise.
“Our sensors solve that problem by measuring vibrations of the vocal cords,” Dr. Rogers said. “But they only work when worn directly on the throat, which is a sensitive area of the skin. We developed novel materials for this sensor that bend and stretch with the body, minimizing discomfort to patients.”
Shirley Ryan AbilityLab uses the throat sensor in conjunction with electronic biosensors, also developed in Dr. Rogers’s laboratory, on the legs, arms, and chest to monitor stroke patients’ recovery progress. The intermodal system of sensors streams data wirelessly to clinicians’ phones and computers, providing a quantitative picture of patients’ advanced physical and physiologic responses in real time.“One of the biggest problems we face with stroke patients is that their gains tend to drop off when they leave the hospital,” said Arun Jayaraman, PhD, research scientist at the Shirley Ryan AbilityLab. “With the home monitoring enabled by these sensors, we can intervene at the right time, which could lead to better, faster recoveries for patients.”
Because the sensors are wireless, they eliminate barriers posed by traditional health monitoring devices in clinical settings. Patients can wear them after they leave the hospital, allowing doctors to understand how their patients are functioning in the real world.
“Talking with friends and family at home is a completely different dimension from what we do in therapy,” said Leora Cherney, PhD, research scientist at the Shirley Ryan AbilityLab. “Having a detailed understanding of patients’ communication habits outside of the clinic helps us develop better strategies with our patients to improve their speaking skills and speed up their recovery process.”
Data from the sensors will be presented in a dashboard that is easy for clinicians and patients to understand. It will send alerts when patients are underperforming on a certain metric and allow them to set and track progress toward their goals.
Inhibiting an Enzyme May Aid Memory Creation
Aging or impaired brains can once again form lasting memories if an enzyme that impedes the function of a key gene too strongly is inhibited, according to neurobiologists at the University of California, Irvine.
“What we have discovered is that if we free up that DNA again, now the aging brain can form long-term memories normally,” said senior author Marcelo Wood, PhD, Francisco J. Ayala Chair in Neurobiology and Behavior at the university. “To form a long-term memory, you have to turn specific genes on. In most young brains, that happens easily, but as we get older and our brains get older, we have trouble with that.”
That is because the six feet of DNA spooled into every cell in our bodies has a harder time releasing itself as needed, he explained. Like many body parts, “it is no longer as flexible as it used to be,” said Dr. Wood. The stiffness in this case is due to a molecular brake pad called histone deacetylase 3 (HDAC3), that has become “overeager” in the aged brain and is compacting the material too hard, blocking the release of a gene called Period1, said Dr. Wood. Removing HDAC3 restores flexibility and allows internal cell machinery to access Period1 to begin forming new memories.
Researchers had previously theorized that the loss of transcription and encoding functions in older brains resulted from deteriorating core circadian clocks. But Dr. Wood and his team found that the ability to create lasting memories was linked to a different process—the enzyme blocking the release of Period1—in the hippocampus.
“New drugs targeting HDAC3 could provide an exciting avenue to allow older people to improve memory formation,” said Dr. Wood.
Unaffected Hemisphere Assumes Language Function After Perinatal Stroke
Babies sometimes have stroke around the time of birth. Birth is hard on the brain, as is the change in blood circulation from the mother to the neonate. At least one in 4,000 babies have stroke shortly before, during, or after birth.
But a stroke in a baby, even a big one, does not have the same lasting impact as a stroke in an adult. A study led by investigators at Georgetown University Medical Center in Washington, DC, found that a decade or two after a perinatal stroke damaged the left language side of the brain, affected teenagers and young adults used the right sides of their brains for language.The findings demonstrate how plastic brain function is in infants, said Elissa L. Newport, PhD, Professor of Neurology at Georgetown University School of Medicine, and Director of the Center for Brain Plasticity and Recovery at Georgetown University and MedStar National Rehabilitation Network.Her study found that the 12 individuals studied, aged 12 to 25, who had a left-brain perinatal stroke all used the right side of their brains for language. “Their language is good—normal,” she said.
The only signs of prior damage to their brains are that some participants limp, and many have learned to make their left hands dominant because their right hands had impaired function after stroke. They also have executive function impairments—slightly slower neural processing, for example—that are common in individuals with brain injuries. But basic cognitive functions, like language comprehension and production, are excellent, said Dr. Newport.
Furthermore, imaging studies revealed that language in these participants is based entirely in the right hemisphere, in the region opposite to the normal language areas in the left hemisphere. This result had been recorded in previous research, but earlier findings were inconsistent, perhaps because of the heterogeneity of the types of brain injuries included in those studies, said Dr. Newport. Her research, which was carefully controlled in terms of the types and areas of injury included, suggests that while “these young brains were plastic, meaning they could relocate language to a healthy area, it does not mean that new areas can be located willy-nilly on the right side.
“We believe there are important constraints on where functions can be relocated,” she continued. “There are specific regions that take over when part of the brain is injured, depending on the particular function. Each function, like language or spatial skills, has a particular region that can take over if its primary brain area is injured. This is an important discovery that may have implications in the rehabilitation of adult stroke survivors.”
This finding is consistent with the behavior of young brains, said Dr. Newport. “Imaging shows that children up to about age 4 can process language in both sides of their brains, and then the functions split up: the left side processes sentences, and the right processes emotion in language.”
Dr. Newport and her colleagues are extending their study of brain function after a perinatal stroke to a larger group of participants. They are examining stroke in the left and right hemispheres and also whether brain functions other than language are relocated and where. Her group is also collaborating on studies that may reveal the molecular basis of plasticity in young brains. This information might help promote plasticity in adults with stroke or brain injury.
Why Do We Sleep?
Evidence supports the synaptic homeostasis hypothesis about the function of sleep, said researchers. The debate about sleep’s function has continued for a generation and arose following observations that people and animals sicken and die if they are deprived of sleep.
Chiara Cirelli, MD, PhD, and Giulio Tononi, MD, PhD, psychiatrists at the Center for Sleep and Consciousness in Madison, Wisconsin, proposed the synaptic homeostasis hypothesis in 2003. This hypothesis holds that sleep is the price we pay for brains that are plastic and able to keep learning new things. They subsequently undertook a four-year research effort that could show direct evidence for their theory. The result was published in February 2017 in Science and offered direct visual proof of the hypothesis.
Striking electron-microscope pictures from inside the brains of mice suggest what happens in our own brains every day. Our synapses grow strong and large during the stimulation of daytime, then shrink by nearly 20% while we sleep, thus creating room for more growth and learning the next day.
A large team of researchers sectioned the brains of mice and used a scanning electron microscope to photograph, reconstruct, and analyze two areas of cerebral cortex. They were able to reconstruct 6,920 synapses and measure their size.
The team remained blinded about whether they were analyzing the brain cells of a well-rested mouse or one that had been awake. When they finally correlated the measurements with the amount of sleep the mice had had during the six to eight hours before the image was taken, they found that a few hours of sleep led on average to an 18% decrease in the size of the synapses. These changes occurred in both areas of the cerebral cortex and were proportional to the size of the synapses.
Dr. Cirelli’s laboratory is now looking at new brain areas, and at the brains of young mice, to understand the role that sleep plays in brain development.
Statistics and Neuroscience Can Improve Anesthesiology
Anesthesia is believed to act on the brain, but the standard protocol among anesthesiologists for monitoring and dosing patients during surgery is to rely on indirect signs of arousal, like movement and changes in heart rate and blood pressure. Research in brain science and statistical modeling has allowed Emery N. Brown, MD, PhD, an anesthetist at Massachusetts General Hospital in Boston, to safely give patients less anesthesia, which can be beneficial.
Dr. Brown has developed a theoretical (ie, neuroscientific) and analytical (ie, statistical) understanding of EEG brain wave measurements of patients under general anesthesia. Anesthesia’s effects in the brain produce specific patterns of brain waves, and monitoring them via EEG data can improve care.
“We should use neuroscience and neuroscience paradigms to try to understand what is happening in the brain under general anesthesia,” said Dr. Brown. “It is a neurophysiologic process that affects the brain and CNS, so how can it be that what is being developed in the neuroscience field is not being brought to bear on the question of the brain under anesthesia?”
In numerous papers over more than a decade, Dr. Brown has examined how various anesthesia drugs such as propofol, dexmedetomidine, and sevoflurane interact with various neuronal receptors, affecting circuits in different regions of the brain. Those neurophysiologic effects ultimately give rise to a state of unconsciousness—essentially a reversible coma—characterized by powerful, low-frequency brain waves that overwhelm the normal rhythms that synchronize brain functions such as sensory perception, higher cognition, or motor control.
Understanding anesthesia to this degree allows for practical insights. In a study published in October 2016 in Proceedings of the National Academy of Sciences, for example, Dr. Brown and colleagues showed how stimulating dopamine-producing neurons in the ventral tegmental area of the brain could wake mice up from general anesthesia. The study suggests a way that human patients could be awakened as well, which could lessen side effects, recover normal brain function more rapidly, and help patients move more quickly out of the operating room and into recovery.
In parallel with illuminating the neuroscience of general anesthesia, Dr. Brown has developed statistical methods to analyze EEG measurements in a way that anesthesiologists can apply to patients. Dr. Brown has shown that EEG readings of level of unconsciousness vary in characteristic ways based on the drug, its dose, and the patient’s age.
“The deciphering of how these drugs are acting in the brain turns out to be an important signal-processing question,” said Dr. Brown. “The drugs work by producing oscillations, these oscillations are readily visible in the EEG and change systematically with drug dose, class, and age.”
During every surgery, Dr. Brown uses real-time EEG readings to keep a patient adequately dosed without giving too much anesthetic. While treating an 81-year-old patient with cancer, Dr. Brown was able to administer about one-third of the dose considered necessary. This dose reduction can be especially important for older patients. “We already know you do not have to give older people as much, but it turns out it can be even less,” said Dr. Brown.
Older patients are especially susceptible to problematic side effects when they wake up, including delirium or postoperative cognitive dysfunction. Neuroscientifically informed ways to prevent giving too much anesthesia can help prevent such problems, said Dr. Brown.
As more anesthesiologists acquire knowledge and EEG equipment, the field can move to a model where doctors have a direct view of the patient’s brain when monitoring and maintaining their consciousness during surgery, said Dr. Brown.
Stretchable Electronics Could Aid Stroke Recovery Treatment
A device designed to be worn on the throat could aid stroke rehabilitation, researchers said.
John A. Rogers, PhD, Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering, and Neurological Surgery at Northwestern University in Evanston, Illinois, developed the device in partnership with Shirley Ryan AbilityLab, a research hospital in Chicago. The sensor is the latest in Dr. Rogers’s portfolio of stretchable electronics that are appropriate for use in advanced medical care and portable enough to be worn outside the hospital and during exercise.
Dr. Rogers’s sensors stick directly to the skin, moving with the body and providing measurements, including heart function, muscle activity, and quality of sleep.
“Stretchable electronics allow us to see what is going on inside patients’ bodies at a level traditional wearables simply cannot achieve,” said Dr. Rogers. “The key is to make them as integrated as possible with the human body.”
The new bandage-like throat sensor measures patients’ swallowing ability and patterns of speech. The sensors aid in the diagnosis and treatment of aphasia.
The tools that speech-language pathologists have traditionally used to monitor patients’ speech function, such as microphones, cannot distinguish between patients’ voices and ambient noise.
“Our sensors solve that problem by measuring vibrations of the vocal cords,” Dr. Rogers said. “But they only work when worn directly on the throat, which is a sensitive area of the skin. We developed novel materials for this sensor that bend and stretch with the body, minimizing discomfort to patients.”
Shirley Ryan AbilityLab uses the throat sensor in conjunction with electronic biosensors, also developed in Dr. Rogers’s laboratory, on the legs, arms, and chest to monitor stroke patients’ recovery progress. The intermodal system of sensors streams data wirelessly to clinicians’ phones and computers, providing a quantitative picture of patients’ advanced physical and physiologic responses in real time.“One of the biggest problems we face with stroke patients is that their gains tend to drop off when they leave the hospital,” said Arun Jayaraman, PhD, research scientist at the Shirley Ryan AbilityLab. “With the home monitoring enabled by these sensors, we can intervene at the right time, which could lead to better, faster recoveries for patients.”
Because the sensors are wireless, they eliminate barriers posed by traditional health monitoring devices in clinical settings. Patients can wear them after they leave the hospital, allowing doctors to understand how their patients are functioning in the real world.
“Talking with friends and family at home is a completely different dimension from what we do in therapy,” said Leora Cherney, PhD, research scientist at the Shirley Ryan AbilityLab. “Having a detailed understanding of patients’ communication habits outside of the clinic helps us develop better strategies with our patients to improve their speaking skills and speed up their recovery process.”
Data from the sensors will be presented in a dashboard that is easy for clinicians and patients to understand. It will send alerts when patients are underperforming on a certain metric and allow them to set and track progress toward their goals.
Inhibiting an Enzyme May Aid Memory Creation
Aging or impaired brains can once again form lasting memories if an enzyme that impedes the function of a key gene too strongly is inhibited, according to neurobiologists at the University of California, Irvine.
“What we have discovered is that if we free up that DNA again, now the aging brain can form long-term memories normally,” said senior author Marcelo Wood, PhD, Francisco J. Ayala Chair in Neurobiology and Behavior at the university. “To form a long-term memory, you have to turn specific genes on. In most young brains, that happens easily, but as we get older and our brains get older, we have trouble with that.”
That is because the six feet of DNA spooled into every cell in our bodies has a harder time releasing itself as needed, he explained. Like many body parts, “it is no longer as flexible as it used to be,” said Dr. Wood. The stiffness in this case is due to a molecular brake pad called histone deacetylase 3 (HDAC3), that has become “overeager” in the aged brain and is compacting the material too hard, blocking the release of a gene called Period1, said Dr. Wood. Removing HDAC3 restores flexibility and allows internal cell machinery to access Period1 to begin forming new memories.
Researchers had previously theorized that the loss of transcription and encoding functions in older brains resulted from deteriorating core circadian clocks. But Dr. Wood and his team found that the ability to create lasting memories was linked to a different process—the enzyme blocking the release of Period1—in the hippocampus.
“New drugs targeting HDAC3 could provide an exciting avenue to allow older people to improve memory formation,” said Dr. Wood.
Unaffected Hemisphere Assumes Language Function After Perinatal Stroke
Babies sometimes have stroke around the time of birth. Birth is hard on the brain, as is the change in blood circulation from the mother to the neonate. At least one in 4,000 babies have stroke shortly before, during, or after birth.
But a stroke in a baby, even a big one, does not have the same lasting impact as a stroke in an adult. A study led by investigators at Georgetown University Medical Center in Washington, DC, found that a decade or two after a perinatal stroke damaged the left language side of the brain, affected teenagers and young adults used the right sides of their brains for language.The findings demonstrate how plastic brain function is in infants, said Elissa L. Newport, PhD, Professor of Neurology at Georgetown University School of Medicine, and Director of the Center for Brain Plasticity and Recovery at Georgetown University and MedStar National Rehabilitation Network.Her study found that the 12 individuals studied, aged 12 to 25, who had a left-brain perinatal stroke all used the right side of their brains for language. “Their language is good—normal,” she said.
The only signs of prior damage to their brains are that some participants limp, and many have learned to make their left hands dominant because their right hands had impaired function after stroke. They also have executive function impairments—slightly slower neural processing, for example—that are common in individuals with brain injuries. But basic cognitive functions, like language comprehension and production, are excellent, said Dr. Newport.
Furthermore, imaging studies revealed that language in these participants is based entirely in the right hemisphere, in the region opposite to the normal language areas in the left hemisphere. This result had been recorded in previous research, but earlier findings were inconsistent, perhaps because of the heterogeneity of the types of brain injuries included in those studies, said Dr. Newport. Her research, which was carefully controlled in terms of the types and areas of injury included, suggests that while “these young brains were plastic, meaning they could relocate language to a healthy area, it does not mean that new areas can be located willy-nilly on the right side.
“We believe there are important constraints on where functions can be relocated,” she continued. “There are specific regions that take over when part of the brain is injured, depending on the particular function. Each function, like language or spatial skills, has a particular region that can take over if its primary brain area is injured. This is an important discovery that may have implications in the rehabilitation of adult stroke survivors.”
This finding is consistent with the behavior of young brains, said Dr. Newport. “Imaging shows that children up to about age 4 can process language in both sides of their brains, and then the functions split up: the left side processes sentences, and the right processes emotion in language.”
Dr. Newport and her colleagues are extending their study of brain function after a perinatal stroke to a larger group of participants. They are examining stroke in the left and right hemispheres and also whether brain functions other than language are relocated and where. Her group is also collaborating on studies that may reveal the molecular basis of plasticity in young brains. This information might help promote plasticity in adults with stroke or brain injury.
Why Do We Sleep?
Evidence supports the synaptic homeostasis hypothesis about the function of sleep, said researchers. The debate about sleep’s function has continued for a generation and arose following observations that people and animals sicken and die if they are deprived of sleep.
Chiara Cirelli, MD, PhD, and Giulio Tononi, MD, PhD, psychiatrists at the Center for Sleep and Consciousness in Madison, Wisconsin, proposed the synaptic homeostasis hypothesis in 2003. This hypothesis holds that sleep is the price we pay for brains that are plastic and able to keep learning new things. They subsequently undertook a four-year research effort that could show direct evidence for their theory. The result was published in February 2017 in Science and offered direct visual proof of the hypothesis.
Striking electron-microscope pictures from inside the brains of mice suggest what happens in our own brains every day. Our synapses grow strong and large during the stimulation of daytime, then shrink by nearly 20% while we sleep, thus creating room for more growth and learning the next day.
A large team of researchers sectioned the brains of mice and used a scanning electron microscope to photograph, reconstruct, and analyze two areas of cerebral cortex. They were able to reconstruct 6,920 synapses and measure their size.
The team remained blinded about whether they were analyzing the brain cells of a well-rested mouse or one that had been awake. When they finally correlated the measurements with the amount of sleep the mice had had during the six to eight hours before the image was taken, they found that a few hours of sleep led on average to an 18% decrease in the size of the synapses. These changes occurred in both areas of the cerebral cortex and were proportional to the size of the synapses.
Dr. Cirelli’s laboratory is now looking at new brain areas, and at the brains of young mice, to understand the role that sleep plays in brain development.
Statistics and Neuroscience Can Improve Anesthesiology
Anesthesia is believed to act on the brain, but the standard protocol among anesthesiologists for monitoring and dosing patients during surgery is to rely on indirect signs of arousal, like movement and changes in heart rate and blood pressure. Research in brain science and statistical modeling has allowed Emery N. Brown, MD, PhD, an anesthetist at Massachusetts General Hospital in Boston, to safely give patients less anesthesia, which can be beneficial.
Dr. Brown has developed a theoretical (ie, neuroscientific) and analytical (ie, statistical) understanding of EEG brain wave measurements of patients under general anesthesia. Anesthesia’s effects in the brain produce specific patterns of brain waves, and monitoring them via EEG data can improve care.
“We should use neuroscience and neuroscience paradigms to try to understand what is happening in the brain under general anesthesia,” said Dr. Brown. “It is a neurophysiologic process that affects the brain and CNS, so how can it be that what is being developed in the neuroscience field is not being brought to bear on the question of the brain under anesthesia?”
In numerous papers over more than a decade, Dr. Brown has examined how various anesthesia drugs such as propofol, dexmedetomidine, and sevoflurane interact with various neuronal receptors, affecting circuits in different regions of the brain. Those neurophysiologic effects ultimately give rise to a state of unconsciousness—essentially a reversible coma—characterized by powerful, low-frequency brain waves that overwhelm the normal rhythms that synchronize brain functions such as sensory perception, higher cognition, or motor control.
Understanding anesthesia to this degree allows for practical insights. In a study published in October 2016 in Proceedings of the National Academy of Sciences, for example, Dr. Brown and colleagues showed how stimulating dopamine-producing neurons in the ventral tegmental area of the brain could wake mice up from general anesthesia. The study suggests a way that human patients could be awakened as well, which could lessen side effects, recover normal brain function more rapidly, and help patients move more quickly out of the operating room and into recovery.
In parallel with illuminating the neuroscience of general anesthesia, Dr. Brown has developed statistical methods to analyze EEG measurements in a way that anesthesiologists can apply to patients. Dr. Brown has shown that EEG readings of level of unconsciousness vary in characteristic ways based on the drug, its dose, and the patient’s age.
“The deciphering of how these drugs are acting in the brain turns out to be an important signal-processing question,” said Dr. Brown. “The drugs work by producing oscillations, these oscillations are readily visible in the EEG and change systematically with drug dose, class, and age.”
During every surgery, Dr. Brown uses real-time EEG readings to keep a patient adequately dosed without giving too much anesthetic. While treating an 81-year-old patient with cancer, Dr. Brown was able to administer about one-third of the dose considered necessary. This dose reduction can be especially important for older patients. “We already know you do not have to give older people as much, but it turns out it can be even less,” said Dr. Brown.
Older patients are especially susceptible to problematic side effects when they wake up, including delirium or postoperative cognitive dysfunction. Neuroscientifically informed ways to prevent giving too much anesthesia can help prevent such problems, said Dr. Brown.
As more anesthesiologists acquire knowledge and EEG equipment, the field can move to a model where doctors have a direct view of the patient’s brain when monitoring and maintaining their consciousness during surgery, said Dr. Brown.
Team engagement and motivation critical to QI success
Thomas McIlraith, MD, SFHM, CLHM, never imagined he would be leading hospitalists and launching quality improvement (QI) initiatives, but only one year out of residency, he was doing just that.
In 2000, Dr. McIlraith had spent a year working as a hospitalist at South Sacramento (Calif.) Kaiser Permanente when he was tapped for the QI program director role.
“Obviously I didn’t have a lot of preparation,” he said of that first job as director. “All of a sudden I found myself in charge of 15 hospitalists, … and I really didn’t know what I was getting myself into.”
But a passion for quality improvement – for striving to always find ways to do better – put Dr. McIlraith on that path and kept him on it through two terms as chair of the hospital medicine department of Mercy Medical Group in Sacramento, where he was hired in 2004. He completed his second term in June 2016 (the department quintupled in size during his tenure), and then chose to return to the ranks as a hospitalist focusing on patient care – and on spending time with his kids before they finished high school.
But quality improvement is in his blood, and he can see himself returning to it someday, Dr. McIlraith said.
“For me it was never about rising up in the ranks of leadership. It was really about making the world I exist in better,” he said.
In recounting some of the lessons he learned over the last 17 years, Dr. McIlraith recalled his first and all-time favorite quality initiative: Central Coordination. It was a concept he implemented around 2002 at Kaiser Permanante that fundamentally changed the way patients were admitted from the emergency department.
The previous system had separate admitting and rounding physicians, which lead to too many patient hand-offs, increased risk of mistakes, poor efficiency, and low patient satisfaction, he said.
“We actually took the job of distributing patients out of physicians’ hands altogether,” Dr. McIlraith explained.
Under Central Coordination, patient assignments were coordinated by a clerical staffer who distributed them evenly among a team of six doctors.
“The most amazing thing was that after this was implemented we went back and looked at ER responsiveness, and our ability to respond to the needs of the ER improved dramatically,” he said. “That wasn’t even an outcome I intended to impact, or look at, but the data were unequivocal. It ended up being really enduring and substantial on many fronts.”
Mercy Medical Group still uses Central Coordination systemwide, and the results of Dr. McIlraith’s initiative were eventually published.
“At the same time, due to my lack of experience in 2002, I definitely made some mistakes,” he said of the undertaking. Among them was failing to recognize just how resistant people can be to change. “I thought [the plan] was so brilliant that everyone would see that and get in line behind me,” he said. “Then I had a rude awakening that not everyone sees things the same way I do. I was completely taken aback by the resistance.”
Even though the existing system left a lot to be desired, the doctors were comfortable with it, Dr. McIlraith explained, stressing that implementing change requires the buy-in of team members.
If he could do it over again, he would follow the eight-step “Road Map for Change” as outlined by Jeffrey Glasheen, MD, SFHM, during the Society of Hospital Medicine’s Leadership Academy, Dr. McIlraith said.
Dr. Glasheen’s road map emphasizes team engagement and motivation, as well as the importance of creating a “burning platform” (the imperative for change).
“You need to be systematic about it to get people to change behaviors,” Dr. McIlraith said, noting that behavioral change is one of the greatest challenges and one of the leading causes of failure to attain the “holy grail” of quality improvement: sustained results.
In fact, the main reason for the enduring success of Central Coordination was that it took the focus off of behavioral change and put it on the process. “We took the behavior aspect out of the equation and put form over function,” Dr. McIlraith said.
One recent quality improvement initiative involved increasing the percentage of discharge orders delivered before 11 a.m. Dr. McIlraith put the lessons he learned to work by creating an “excellence team” that met regularly to identify key problems and to create “SMART (Specific, Measurable, Attainable, Relevant, and Timely) goals,” which are necessary for success.
Because the team not only bought into the plan to meet the target but also helped create the plan, it wasn’t necessary to force behavioral change, Dr. McIlraith said. Instead the team lead the initiative, set the targets and goals, and ended up surpassing the initial goal of reaching 30% of discharge orders in by 11 a.m. (in fact, they hit 40%).
Dr. McIlraith’s advice for QI success is to know the problem you are trying to solve so that you can tell if the solution you implement is having the desired impact and also to measure the impact of that solution using the SMART goals.
For those who hope to follow a quality improvement career path to leadership, he strongly recommends the Society of Hospital Medicine’s Leadership Academies, which are excellent resources for mentorship, networking, and leadership training through SHM.
Ultimately, Dr. McIlraith stressed the importance of mentoring team members for development as future QI leaders. If mentoring relationships are successful, then when the time comes for a QI veteran to “step back” to focus more on family or take a different career path, there will be others who can step in and keep the quality momentum going.
Thomas McIlraith, MD, SFHM, CLHM, never imagined he would be leading hospitalists and launching quality improvement (QI) initiatives, but only one year out of residency, he was doing just that.
In 2000, Dr. McIlraith had spent a year working as a hospitalist at South Sacramento (Calif.) Kaiser Permanente when he was tapped for the QI program director role.
“Obviously I didn’t have a lot of preparation,” he said of that first job as director. “All of a sudden I found myself in charge of 15 hospitalists, … and I really didn’t know what I was getting myself into.”
But a passion for quality improvement – for striving to always find ways to do better – put Dr. McIlraith on that path and kept him on it through two terms as chair of the hospital medicine department of Mercy Medical Group in Sacramento, where he was hired in 2004. He completed his second term in June 2016 (the department quintupled in size during his tenure), and then chose to return to the ranks as a hospitalist focusing on patient care – and on spending time with his kids before they finished high school.
But quality improvement is in his blood, and he can see himself returning to it someday, Dr. McIlraith said.
“For me it was never about rising up in the ranks of leadership. It was really about making the world I exist in better,” he said.
In recounting some of the lessons he learned over the last 17 years, Dr. McIlraith recalled his first and all-time favorite quality initiative: Central Coordination. It was a concept he implemented around 2002 at Kaiser Permanante that fundamentally changed the way patients were admitted from the emergency department.
The previous system had separate admitting and rounding physicians, which lead to too many patient hand-offs, increased risk of mistakes, poor efficiency, and low patient satisfaction, he said.
“We actually took the job of distributing patients out of physicians’ hands altogether,” Dr. McIlraith explained.
Under Central Coordination, patient assignments were coordinated by a clerical staffer who distributed them evenly among a team of six doctors.
“The most amazing thing was that after this was implemented we went back and looked at ER responsiveness, and our ability to respond to the needs of the ER improved dramatically,” he said. “That wasn’t even an outcome I intended to impact, or look at, but the data were unequivocal. It ended up being really enduring and substantial on many fronts.”
Mercy Medical Group still uses Central Coordination systemwide, and the results of Dr. McIlraith’s initiative were eventually published.
“At the same time, due to my lack of experience in 2002, I definitely made some mistakes,” he said of the undertaking. Among them was failing to recognize just how resistant people can be to change. “I thought [the plan] was so brilliant that everyone would see that and get in line behind me,” he said. “Then I had a rude awakening that not everyone sees things the same way I do. I was completely taken aback by the resistance.”
Even though the existing system left a lot to be desired, the doctors were comfortable with it, Dr. McIlraith explained, stressing that implementing change requires the buy-in of team members.
If he could do it over again, he would follow the eight-step “Road Map for Change” as outlined by Jeffrey Glasheen, MD, SFHM, during the Society of Hospital Medicine’s Leadership Academy, Dr. McIlraith said.
Dr. Glasheen’s road map emphasizes team engagement and motivation, as well as the importance of creating a “burning platform” (the imperative for change).
“You need to be systematic about it to get people to change behaviors,” Dr. McIlraith said, noting that behavioral change is one of the greatest challenges and one of the leading causes of failure to attain the “holy grail” of quality improvement: sustained results.
In fact, the main reason for the enduring success of Central Coordination was that it took the focus off of behavioral change and put it on the process. “We took the behavior aspect out of the equation and put form over function,” Dr. McIlraith said.
One recent quality improvement initiative involved increasing the percentage of discharge orders delivered before 11 a.m. Dr. McIlraith put the lessons he learned to work by creating an “excellence team” that met regularly to identify key problems and to create “SMART (Specific, Measurable, Attainable, Relevant, and Timely) goals,” which are necessary for success.
Because the team not only bought into the plan to meet the target but also helped create the plan, it wasn’t necessary to force behavioral change, Dr. McIlraith said. Instead the team lead the initiative, set the targets and goals, and ended up surpassing the initial goal of reaching 30% of discharge orders in by 11 a.m. (in fact, they hit 40%).
Dr. McIlraith’s advice for QI success is to know the problem you are trying to solve so that you can tell if the solution you implement is having the desired impact and also to measure the impact of that solution using the SMART goals.
For those who hope to follow a quality improvement career path to leadership, he strongly recommends the Society of Hospital Medicine’s Leadership Academies, which are excellent resources for mentorship, networking, and leadership training through SHM.
Ultimately, Dr. McIlraith stressed the importance of mentoring team members for development as future QI leaders. If mentoring relationships are successful, then when the time comes for a QI veteran to “step back” to focus more on family or take a different career path, there will be others who can step in and keep the quality momentum going.
Thomas McIlraith, MD, SFHM, CLHM, never imagined he would be leading hospitalists and launching quality improvement (QI) initiatives, but only one year out of residency, he was doing just that.
In 2000, Dr. McIlraith had spent a year working as a hospitalist at South Sacramento (Calif.) Kaiser Permanente when he was tapped for the QI program director role.
“Obviously I didn’t have a lot of preparation,” he said of that first job as director. “All of a sudden I found myself in charge of 15 hospitalists, … and I really didn’t know what I was getting myself into.”
But a passion for quality improvement – for striving to always find ways to do better – put Dr. McIlraith on that path and kept him on it through two terms as chair of the hospital medicine department of Mercy Medical Group in Sacramento, where he was hired in 2004. He completed his second term in June 2016 (the department quintupled in size during his tenure), and then chose to return to the ranks as a hospitalist focusing on patient care – and on spending time with his kids before they finished high school.
But quality improvement is in his blood, and he can see himself returning to it someday, Dr. McIlraith said.
“For me it was never about rising up in the ranks of leadership. It was really about making the world I exist in better,” he said.
In recounting some of the lessons he learned over the last 17 years, Dr. McIlraith recalled his first and all-time favorite quality initiative: Central Coordination. It was a concept he implemented around 2002 at Kaiser Permanante that fundamentally changed the way patients were admitted from the emergency department.
The previous system had separate admitting and rounding physicians, which lead to too many patient hand-offs, increased risk of mistakes, poor efficiency, and low patient satisfaction, he said.
“We actually took the job of distributing patients out of physicians’ hands altogether,” Dr. McIlraith explained.
Under Central Coordination, patient assignments were coordinated by a clerical staffer who distributed them evenly among a team of six doctors.
“The most amazing thing was that after this was implemented we went back and looked at ER responsiveness, and our ability to respond to the needs of the ER improved dramatically,” he said. “That wasn’t even an outcome I intended to impact, or look at, but the data were unequivocal. It ended up being really enduring and substantial on many fronts.”
Mercy Medical Group still uses Central Coordination systemwide, and the results of Dr. McIlraith’s initiative were eventually published.
“At the same time, due to my lack of experience in 2002, I definitely made some mistakes,” he said of the undertaking. Among them was failing to recognize just how resistant people can be to change. “I thought [the plan] was so brilliant that everyone would see that and get in line behind me,” he said. “Then I had a rude awakening that not everyone sees things the same way I do. I was completely taken aback by the resistance.”
Even though the existing system left a lot to be desired, the doctors were comfortable with it, Dr. McIlraith explained, stressing that implementing change requires the buy-in of team members.
If he could do it over again, he would follow the eight-step “Road Map for Change” as outlined by Jeffrey Glasheen, MD, SFHM, during the Society of Hospital Medicine’s Leadership Academy, Dr. McIlraith said.
Dr. Glasheen’s road map emphasizes team engagement and motivation, as well as the importance of creating a “burning platform” (the imperative for change).
“You need to be systematic about it to get people to change behaviors,” Dr. McIlraith said, noting that behavioral change is one of the greatest challenges and one of the leading causes of failure to attain the “holy grail” of quality improvement: sustained results.
In fact, the main reason for the enduring success of Central Coordination was that it took the focus off of behavioral change and put it on the process. “We took the behavior aspect out of the equation and put form over function,” Dr. McIlraith said.
One recent quality improvement initiative involved increasing the percentage of discharge orders delivered before 11 a.m. Dr. McIlraith put the lessons he learned to work by creating an “excellence team” that met regularly to identify key problems and to create “SMART (Specific, Measurable, Attainable, Relevant, and Timely) goals,” which are necessary for success.
Because the team not only bought into the plan to meet the target but also helped create the plan, it wasn’t necessary to force behavioral change, Dr. McIlraith said. Instead the team lead the initiative, set the targets and goals, and ended up surpassing the initial goal of reaching 30% of discharge orders in by 11 a.m. (in fact, they hit 40%).
Dr. McIlraith’s advice for QI success is to know the problem you are trying to solve so that you can tell if the solution you implement is having the desired impact and also to measure the impact of that solution using the SMART goals.
For those who hope to follow a quality improvement career path to leadership, he strongly recommends the Society of Hospital Medicine’s Leadership Academies, which are excellent resources for mentorship, networking, and leadership training through SHM.
Ultimately, Dr. McIlraith stressed the importance of mentoring team members for development as future QI leaders. If mentoring relationships are successful, then when the time comes for a QI veteran to “step back” to focus more on family or take a different career path, there will be others who can step in and keep the quality momentum going.
Migraine May Be an Important Risk Factor for Cardiovascular Diseases
Migraine is associated with increased risk of myocardial infarction, ischemic stroke, hemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter, according to a study published online ahead of print January 31 in BMJ. The results suggest that “migraine should be considered a potent and persistent risk factor for most cardiovascular diseases in both men and women,” the researchers said.
Prior studies have found that migraine is associated with ischemic stroke and ischemic heart disease, especially among women and patients with migraine with aura. Convincing epidemiologic evidence of an association between migraine and other cardiovascular events has been lacking, however, said Kasper Adelborg, MD, PhD, of the Department of Clinical Epidemiology at Aarhus University Hospital in Denmark, and colleagues. 
To study cardiovascular morbidity associated with migraine, Dr. Adelborg and colleagues conducted a nationwide, population-based cohort study. The study included patients from all Danish hospitals and hospital outpatient clinics between 1995 and 2013. The researchers used Cox regression analysis to assess comorbidity-adjusted hazard ratios of cardiovascular outcomes.
Their analysis included 51,032 patients with migraine and 510,320 people from the general population matched on age, sex, and calendar year. Median age at migraine diagnosis was 35, and 71% of the participants were women.
Incidence per 1,000 People
Patients with incident migraine had greater absolute risk of most cardiovascular outcomes, compared with the general population, across most follow-up periods. After 19 years of follow-up, the cumulative incidences per 1,000 people were greater among migraineurs, compared with the general population, for myocardial infarction (25 vs 17), ischemic stroke (45 vs 25), hemorrhagic stroke (11 vs 6), peripheral artery disease (13 vs 11), venous thromboembolism (27 vs 18), atrial fibrillation or atrial flutter (47 vs 34), and heart failure (19 vs 18).
Migraine was associated with myocardial infarction (adjusted hazard ratio [HR], 1.49), ischemic stroke (adjusted HR, 2.26), and hemorrhagic stroke (adjusted HR, 1.94), as well as venous thromboembolism (adjusted HR, 1.59) and atrial fibrillation or atrial flutter (adjusted HR, 1.25). Migraine was not meaningfully associated with peripheral artery disease or heart failure. “The associations, particularly for stroke outcomes, were stronger during the short term (0–1 years) after diagnosis than the long term (up to 19 years),” the researchers said. In addition, associations were stronger in migraine with aura than in migraine without aura, and in women than in men. In a subcohort of patients with additional data, the associations persisted after additional adjustments for BMI and smoking.
The absolute risk of cardiovascular outcomes was low, which was expected, given the young age of the study population, the researchers noted. Although the investigators adjusted for a range of potential confounders, other unknown or residual confounding (eg, by physical activity) is possible.
Multifactorial mechanisms may explain the observed increased risk of cardiovascular disease in migraine, and different mechanisms may be involved in specific cardiovascular outcomes. Migraine and cardiovascular diseases may share genetic, inflammatory, vascular, endothelial, electrical or depolarizing, or coagulable factors, the researchers said. In addition, migraineurs often use NSAIDs, which are associated with increased risk of cardiovascular events. It is also possible that immobilization due to migraine attacks may increase the risk of venous thromboembolism.
Reducing Risk
“Although the magnitude of the increased cardiovascular risk associated with migraine was fairly small at the individual level, it translates into a substantial increase in risk at the population level, because migraine is a common disease,” Dr. Adelborg and colleagues said. Migraine increasingly is recognized as an important cardiovascular risk factor to consider in clinical practice, and the recently developed QRISK3 algorithm, which predicts 10-year risk of cardiovascular disease in men and women ages 25 to 84, is the first cardiovascular risk-stratification tool to incorporate migraine.
“Ultimately, it will be important to determine whether prevention strategies in patients with migraine can reduce the burden of cardiovascular disease in patients with this common disorder,” the researchers said. “Current migraine guidelines do not recommend use of aspirin and clopidogrel in the prophylaxis of migraine, but clinicians should consider whether patients at particularly high risk of cardiovascular diseases would benefit from anticoagulant treatment.”
The present study and prior research provide “plenty of evidence that migraine should be taken seriously as a strong cardiovascular risk marker,” and data indicate that migraine is associated with “a measurable risk of cardiovascular death,” said Tobias Kurth, MD, Professor of Public Health and Epidemiology and Director of the Institute of Public Health at the Charité-Universitätsmedizin Berlin
Suggested Reading
Adelborg K, Szépligeti SK, Holland-Bill L, et al. Migraine and risk of cardiovascular diseases: Danish population based matched cohort study. BMJ. 2018 Jan 31 [Epub ahead of print].
Kurth T, Rohmann JL, Shapiro RE. Migraine and risk of cardiovascular disease. BMJ. 2018 Jan 31 [Epub ahead of print].
Migraine is associated with increased risk of myocardial infarction, ischemic stroke, hemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter, according to a study published online ahead of print January 31 in BMJ. The results suggest that “migraine should be considered a potent and persistent risk factor for most cardiovascular diseases in both men and women,” the researchers said.
Prior studies have found that migraine is associated with ischemic stroke and ischemic heart disease, especially among women and patients with migraine with aura. Convincing epidemiologic evidence of an association between migraine and other cardiovascular events has been lacking, however, said Kasper Adelborg, MD, PhD, of the Department of Clinical Epidemiology at Aarhus University Hospital in Denmark, and colleagues.
To study cardiovascular morbidity associated with migraine, Dr. Adelborg and colleagues conducted a nationwide, population-based cohort study. The study included patients from all Danish hospitals and hospital outpatient clinics between 1995 and 2013. The researchers used Cox regression analysis to assess comorbidity-adjusted hazard ratios of cardiovascular outcomes.
Their analysis included 51,032 patients with migraine and 510,320 people from the general population matched on age, sex, and calendar year. Median age at migraine diagnosis was 35, and 71% of the participants were women.
Incidence per 1,000 People
Patients with incident migraine had greater absolute risk of most cardiovascular outcomes, compared with the general population, across most follow-up periods. After 19 years of follow-up, the cumulative incidences per 1,000 people were greater among migraineurs, compared with the general population, for myocardial infarction (25 vs 17), ischemic stroke (45 vs 25), hemorrhagic stroke (11 vs 6), peripheral artery disease (13 vs 11), venous thromboembolism (27 vs 18), atrial fibrillation or atrial flutter (47 vs 34), and heart failure (19 vs 18).
Migraine was associated with myocardial infarction (adjusted hazard ratio [HR], 1.49), ischemic stroke (adjusted HR, 2.26), and hemorrhagic stroke (adjusted HR, 1.94), as well as venous thromboembolism (adjusted HR, 1.59) and atrial fibrillation or atrial flutter (adjusted HR, 1.25). Migraine was not meaningfully associated with peripheral artery disease or heart failure. “The associations, particularly for stroke outcomes, were stronger during the short term (0–1 years) after diagnosis than the long term (up to 19 years),” the researchers said. In addition, associations were stronger in migraine with aura than in migraine without aura, and in women than in men. In a subcohort of patients with additional data, the associations persisted after additional adjustments for BMI and smoking.
The absolute risk of cardiovascular outcomes was low, which was expected, given the young age of the study population, the researchers noted. Although the investigators adjusted for a range of potential confounders, other unknown or residual confounding (eg, by physical activity) is possible.
Multifactorial mechanisms may explain the observed increased risk of cardiovascular disease in migraine, and different mechanisms may be involved in specific cardiovascular outcomes. Migraine and cardiovascular diseases may share genetic, inflammatory, vascular, endothelial, electrical or depolarizing, or coagulable factors, the researchers said. In addition, migraineurs often use NSAIDs, which are associated with increased risk of cardiovascular events. It is also possible that immobilization due to migraine attacks may increase the risk of venous thromboembolism.
Reducing Risk
“Although the magnitude of the increased cardiovascular risk associated with migraine was fairly small at the individual level, it translates into a substantial increase in risk at the population level, because migraine is a common disease,” Dr. Adelborg and colleagues said. Migraine increasingly is recognized as an important cardiovascular risk factor to consider in clinical practice, and the recently developed QRISK3 algorithm, which predicts 10-year risk of cardiovascular disease in men and women ages 25 to 84, is the first cardiovascular risk-stratification tool to incorporate migraine.
“Ultimately, it will be important to determine whether prevention strategies in patients with migraine can reduce the burden of cardiovascular disease in patients with this common disorder,” the researchers said. “Current migraine guidelines do not recommend use of aspirin and clopidogrel in the prophylaxis of migraine, but clinicians should consider whether patients at particularly high risk of cardiovascular diseases would benefit from anticoagulant treatment.”
The present study and prior research provide “plenty of evidence that migraine should be taken seriously as a strong cardiovascular risk marker,” and data indicate that migraine is associated with “a measurable risk of cardiovascular death,” said Tobias Kurth, MD, Professor of Public Health and Epidemiology and Director of the Institute of Public Health at the Charité-Universitätsmedizin Berlin
Suggested Reading
Adelborg K, Szépligeti SK, Holland-Bill L, et al. Migraine and risk of cardiovascular diseases: Danish population based matched cohort study. BMJ. 2018 Jan 31 [Epub ahead of print].
Kurth T, Rohmann JL, Shapiro RE. Migraine and risk of cardiovascular disease. BMJ. 2018 Jan 31 [Epub ahead of print].
Migraine is associated with increased risk of myocardial infarction, ischemic stroke, hemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter, according to a study published online ahead of print January 31 in BMJ. The results suggest that “migraine should be considered a potent and persistent risk factor for most cardiovascular diseases in both men and women,” the researchers said.
Prior studies have found that migraine is associated with ischemic stroke and ischemic heart disease, especially among women and patients with migraine with aura. Convincing epidemiologic evidence of an association between migraine and other cardiovascular events has been lacking, however, said Kasper Adelborg, MD, PhD, of the Department of Clinical Epidemiology at Aarhus University Hospital in Denmark, and colleagues.
To study cardiovascular morbidity associated with migraine, Dr. Adelborg and colleagues conducted a nationwide, population-based cohort study. The study included patients from all Danish hospitals and hospital outpatient clinics between 1995 and 2013. The researchers used Cox regression analysis to assess comorbidity-adjusted hazard ratios of cardiovascular outcomes.
Their analysis included 51,032 patients with migraine and 510,320 people from the general population matched on age, sex, and calendar year. Median age at migraine diagnosis was 35, and 71% of the participants were women.
Incidence per 1,000 People
Patients with incident migraine had greater absolute risk of most cardiovascular outcomes, compared with the general population, across most follow-up periods. After 19 years of follow-up, the cumulative incidences per 1,000 people were greater among migraineurs, compared with the general population, for myocardial infarction (25 vs 17), ischemic stroke (45 vs 25), hemorrhagic stroke (11 vs 6), peripheral artery disease (13 vs 11), venous thromboembolism (27 vs 18), atrial fibrillation or atrial flutter (47 vs 34), and heart failure (19 vs 18).
Migraine was associated with myocardial infarction (adjusted hazard ratio [HR], 1.49), ischemic stroke (adjusted HR, 2.26), and hemorrhagic stroke (adjusted HR, 1.94), as well as venous thromboembolism (adjusted HR, 1.59) and atrial fibrillation or atrial flutter (adjusted HR, 1.25). Migraine was not meaningfully associated with peripheral artery disease or heart failure. “The associations, particularly for stroke outcomes, were stronger during the short term (0–1 years) after diagnosis than the long term (up to 19 years),” the researchers said. In addition, associations were stronger in migraine with aura than in migraine without aura, and in women than in men. In a subcohort of patients with additional data, the associations persisted after additional adjustments for BMI and smoking.
The absolute risk of cardiovascular outcomes was low, which was expected, given the young age of the study population, the researchers noted. Although the investigators adjusted for a range of potential confounders, other unknown or residual confounding (eg, by physical activity) is possible.
Multifactorial mechanisms may explain the observed increased risk of cardiovascular disease in migraine, and different mechanisms may be involved in specific cardiovascular outcomes. Migraine and cardiovascular diseases may share genetic, inflammatory, vascular, endothelial, electrical or depolarizing, or coagulable factors, the researchers said. In addition, migraineurs often use NSAIDs, which are associated with increased risk of cardiovascular events. It is also possible that immobilization due to migraine attacks may increase the risk of venous thromboembolism.
Reducing Risk
“Although the magnitude of the increased cardiovascular risk associated with migraine was fairly small at the individual level, it translates into a substantial increase in risk at the population level, because migraine is a common disease,” Dr. Adelborg and colleagues said. Migraine increasingly is recognized as an important cardiovascular risk factor to consider in clinical practice, and the recently developed QRISK3 algorithm, which predicts 10-year risk of cardiovascular disease in men and women ages 25 to 84, is the first cardiovascular risk-stratification tool to incorporate migraine.
“Ultimately, it will be important to determine whether prevention strategies in patients with migraine can reduce the burden of cardiovascular disease in patients with this common disorder,” the researchers said. “Current migraine guidelines do not recommend use of aspirin and clopidogrel in the prophylaxis of migraine, but clinicians should consider whether patients at particularly high risk of cardiovascular diseases would benefit from anticoagulant treatment.”
The present study and prior research provide “plenty of evidence that migraine should be taken seriously as a strong cardiovascular risk marker,” and data indicate that migraine is associated with “a measurable risk of cardiovascular death,” said Tobias Kurth, MD, Professor of Public Health and Epidemiology and Director of the Institute of Public Health at the Charité-Universitätsmedizin Berlin
Suggested Reading
Adelborg K, Szépligeti SK, Holland-Bill L, et al. Migraine and risk of cardiovascular diseases: Danish population based matched cohort study. BMJ. 2018 Jan 31 [Epub ahead of print].
Kurth T, Rohmann JL, Shapiro RE. Migraine and risk of cardiovascular disease. BMJ. 2018 Jan 31 [Epub ahead of print].
Conference News Roundup—Association of Academic Physiatrists
Electrical Stimulation Device Improves Motor Function
A person with a spinal cord injury can improve his or her ability to grip and move household objects by using an electrical stimulation device controlled by his or her thoughts, according to researchers. The study suggests that this new technology could one day enhance quality of life among people with disabilities and allow them to live more independently.
People with tetraplegia lose upper-limb strength and dexterity, which has a severe impact on their independence and quality of life. New technology that connects a person’s brain to an implanted functional electrical stimulation orthotics device on the hands could restore manual dexterity and grip strength, thus allowing him or her to perform simple daily tasks like holding a toothbrush without help.
“Individuals with cervical spinal cord injury identify recovery of the use of their hands as the single most impactful way that neurotechnology could change their lives,” said Marcie Bockbrader, MD, PhD, Assistant Professor of Physical Medicine and Rehabilitation at the Ohio State University Wexner Medical Center in Columbus. “Giving a person back [his or her] hands reduces dependence on others. It makes it possible to do the little things—like cutting food or opening a door—that are so essential to being able to take care of oneself.”
To test how well this thought-controlled brain–computer interface system works in real life to improve hand strength and dexterity, Dr. Bockbrader and her research team surgically implanted one of these devices into the hand of a 26-year-old man with C5-level, nonspastic tetraplegia following a spinal cord injury. He practiced using the device three times per week for four hours each session for more than 1,000 days. The research team administered standardized tests of upper-limb motor ability and functional participation to see how well the system improved his grip strength, quickness, and other basic skills.
Using this device improved the man’s upper-limb motor ability dramatically, according to several standardized tests. He improved his ability to grip and manipulate basic objects, and showed that he could perform ordinary tasks with his hands at the speed and dexterity levels of healthy individuals. He could move objects of different sizes and weights. With practice, he improved his ability to manipulate smaller household objects like a toothbrush or hairbrush. He also demonstrated that he could imagine different hand positions to proportionally adjust and control different hand movements.
“Our study demonstrated that patients with tetraplegia might be able to restore some of their skilled hand function with an implanted device that allows them to control movements with their own thoughts,” said Dr. Bockbrader. “Although this technology must be refined and tested before it can go from the laboratory to the public, it may one day offer people with disabilities a way to live and work more independently, and enable them to perform daily tasks.”
Concussion Recovery Varies Among Children
Not all children follow the same path to concussion recovery, nor do they have the same predictors for returning to normal activity, investigators reported. Their study also suggests that younger children should be considered separately from high-school students.
“Concussions are common among children, yet the literature is limited with regard to understanding trajectory of recovery after concussion, particularly in children with non-sports-related injuries and for younger children,” said Kaitlyn Chin, a second-year medical student at University of New England College of Osteopathic Medicine in Biddeford, Maine. “We were particularly interested in understanding how activity levels during recovery from concussion influence time to full recovery, to be able to identify modifiable factors to help guide concussion care. Previous studies have noted differences in the amount of time it takes children to recover from a concussion, and our team recently initiated a study to see if we can identify predictors associated with the amount of time between injury and when a child is medically cleared to return to activities which place the child at risk for reinjury.”
Ms. Chin’s team at Kennedy Krieger Institute in Baltimore reviewed the medical records of 178 children who were treated for concussions at an academically affiliated, rehabilitation-based clinic. The children had been medically cleared to return to play between September 2015 and February 2017. The children included in the study ranged in age from 6 to 17. A slight majority was younger than 14. Each child’s first visit to the clinic was within 60 days of his or her concussion.
The researchers reviewed each child’s record, noting when they had been approved to return to play. Then they looked at several other factors for each child, including sex, cause of the concussion (ie, sports or non-sports-related), number of symptoms, school attendance, and exercise status at the initial visit to the clinic. Finally, they considered these factors when the children were placed into two categories—children under 14 and children over 14—to examine potential differences related to age.
Ms. Chin’s team found that the number of symptoms affected how quickly all children were cleared to return to play. Fewer symptoms were associated with a faster return to play. For older children, male sex and higher level of exercise during recovery were associated with a faster return to play. For younger children, higher levels of exercise and school participation (eg, attending class and completing homework and tests) were associated with faster return to play.
Overall, this study shows that elementary and middle-school-aged children should be considered separately from high-school-aged students when considering risk factors for prolonged recovery from a concussion. Furthermore, Ms. Chin’s team found that school participation and exercise were not harmful and did not prolong recovery.
“Our study adds to the literature supporting that return to cognitive and safe physical activities while a child is still recovering from concussion does not prolong time to recovery,” said Ms. Chin. “Every child is different, and recovery is different for each concussion. [Therefore], a concussion recovery plan should be tailored for each child, and parents should seek help from the child’s pediatrician or other medical professionals for guiding care after a concussion.”
Medicine May Not Affect Concussion Recovery
Medications commonly prescribed to reduce symptoms of concussion may not affect recovery, said investigators. Sports medicine physicians commonly treat patients with concussion, so researchers in Utah investigated how some widely prescribed treatments might affect patients’ recovery.
“We really do not have much other than rest and gentle exercise to combat symptoms of concussion,” said Venessa Lee, MD, a physical medicine and rehabilitation resident at University of Utah Health in Salt Lake City. “Medications are commonly prescribed to help with symptoms, but there is little evidence that they help more than just time and rest.”
Although FDA has not approved any medication to treat concussion, physicians may prescribe medications like gabapentin or tricyclic antidepressants (TCAs) to help reduce symptoms during recovery. To examine whether these drugs benefit patients, Dr. Lee and her research team looked at 277 patients who had been diagnosed with concussion at a local academic sports medicine practice. At each of their visits to the clinic during recovery, patients reported their postconcussion symptoms. The research team used a score sheet to measure their symptoms, and they tracked scores of patients who had more than one visit to the clinic for as long as one year.
Patients were separated into three groups for the study: those not prescribed any medication, those prescribed gabapentin, and those prescribed one of two TCAs, amitriptyline or nortriptyline. Based on self-reported information, investigators gave each patient a score for two factors of postconcussion recovery: headaches and a combination of 22 symptoms, including headaches. Each score was on a scale of 0 to 6.
After they adjusted scores for gender and age, Dr. Lee’s team found that headache and combined symptoms scores decreased significantly within days after the first clinic visit for all three groups of patients—those who had taken no medications, those who had been prescribed gabapentin, and those who had been prescribed a TCA. Patients who had been prescribed any of the medications had significantly higher scores for headaches and overall postconcussion symptoms to begin with, but no one type of medication had any better or worse effect over the duration of the study.
“Patients’ symptoms improve with time after a concussion,” said Dr. Lee. “When we looked at [patients who received] gabapentin and TCAs, their symptoms improved over time as well, but similar to those that did not receive a medication.”
Based on this study, neither gabapentin nor TCAs appear to provide any additional benefit for postconcussion recovery. With this information, patients may be able to avoid taking unnecessary medications as they recover from concussions. Patients should speak with a physician about their symptoms after a concussion, said Dr. Lee.
“Though the two medications we studied did not show a profound improvement in our analysis, this was a retrospective study … which has many drawbacks and limitations. We need to do more research to really find the best method for improving postconcussive symptoms.”
Ballet Helps Children with Musculoskeletal and Neurologic Conditions
Adaptive ballet classes provide functional improvement and social interactions for children with musculoskeletal and neurologic conditions, according to researchers. This type of arts-based adaptive therapy is a promising expansion to successful adaptive sports therapies, said the investigators.
“While great strides have been made in adaptive sports, there are still relatively few opportunities in the arts for people with disabilities,” said Sarah Stauder, MD, a physician at the Medical College of Wisconsin in Milwaukee. “Because of this [scarcity], we wanted to evaluate the effect of adaptive ballet on the physical, emotional, social, and academic function of children with physical impairments. The program is a collaboration between a children’s hospital and a metropolitan ballet company that brings together professional dancers, pediatric doctors, physical and occupational therapists, and children with physical disabilities for a series of dance classes.”
The goal of the study was to see whether a weekly, 45-mintute ballet class with 15 minutes of ballet education over five consecutive weeks would improve the children’s balance, physical functions, social skills, and overall quality of life. Eighteen children (17 girls) from ages 5 to 14, took part in the class. Assessments of each child were performed before and after the series of classes using the Pediatric Quality of Life Inventory, the PEDI-CAT survey, and the Pediatric Balance Scale. Finally, a questionnaire was used to assess each child’s success in achieving individual goals set for the class.
At the end of the five weeks, 94% of participants reached their individual goals for the ballet program. PEDI-CAT scores improved after completion of the program, and the program was most beneficial to participants who had lower functioning and quality of life at the beginning of the program. Finally, the researchers noticed an average improvement in balance among the participants.
“Adaptive programs like the one studied here give children the opportunity to participate in activities they otherwise would have no way to do,” said Dr. Stauder. “More specifically, these dance classes instilled a sense of pride and confidence in the children while improving their physical functioning and quality of life. Our study should open the door to more arts-based therapy for children. It is an effective and enjoyable way for patients to get the therapy they need. When kids are active in an activity that interests them, they naturally make greater strides, and we were able to see this in their day-to-day function.”
Genetic Risk Score Predicts TBI Outcomes
A genetic risk score could help predict a patient’s quality of life after a traumatic brain injury (TBI), said researchers. One day, physicians could have a simple method to forecast a patient’s recovery and personalize therapy to maximize quality of life.
“Gene pathways can influence all of our biologic functions and risk for many health outcomes,” said Mark Linsenmeyer, MD, a resident physician at the University of Pittsburgh Medical Center. “Each person has a unique inherited genetic code. By studying one gene pathway in a large group of people with the same disease or health problem, we hope to unlock clues to why some people have different outcomes than others. This knowledge may be used to help physicians make the best treatment choice for each person.”
Dr. Linsenmeyer and colleagues set out to investigate how genes that affect the brain’s dopamine pathways could predict recovery in people with moderate-to-severe TBI. The team recruited 94 adults with TBI from a level-1 trauma center. They focused on the following five genes in the dopamine pathways: COMT rs4680, VMAT2 rs363226, DRD2 rs6279, ANKK1 Taq1a, and MAOA VNTR. They defined which risk genotypes were associated with lower average scores on surveys filled out by patients with TBI to describe their overall quality of life at six and 12 months after their injuries.
The researchers analyzed how individual variants of each of these five genes could affect patients’ quality of life, and then generated a weighted gene risk score as a measure to reflect cumulative risk represented by all genotypes included in the score. Based on available literature about dopamine pathway genetics, they predicted that their gene risk score calculation tool should be specific to a patient’s sex.
Before they calculated gene risk scores, the research team noticed that only COMT could significantly predict quality of life for a subset of patients six months after their injuries. After generating sex-specific gene risk scores, they found that variants of all five genes on the dopamine pathway could meaningfully contribute to a gene risk score that was highly predictive of quality of life after six months for patients of both sexes with TBI, and also predictive of quality of life after one year for women.
Electrical Stimulation Device Improves Motor Function
A person with a spinal cord injury can improve his or her ability to grip and move household objects by using an electrical stimulation device controlled by his or her thoughts, according to researchers. The study suggests that this new technology could one day enhance quality of life among people with disabilities and allow them to live more independently.
People with tetraplegia lose upper-limb strength and dexterity, which has a severe impact on their independence and quality of life. New technology that connects a person’s brain to an implanted functional electrical stimulation orthotics device on the hands could restore manual dexterity and grip strength, thus allowing him or her to perform simple daily tasks like holding a toothbrush without help.
“Individuals with cervical spinal cord injury identify recovery of the use of their hands as the single most impactful way that neurotechnology could change their lives,” said Marcie Bockbrader, MD, PhD, Assistant Professor of Physical Medicine and Rehabilitation at the Ohio State University Wexner Medical Center in Columbus. “Giving a person back [his or her] hands reduces dependence on others. It makes it possible to do the little things—like cutting food or opening a door—that are so essential to being able to take care of oneself.”
To test how well this thought-controlled brain–computer interface system works in real life to improve hand strength and dexterity, Dr. Bockbrader and her research team surgically implanted one of these devices into the hand of a 26-year-old man with C5-level, nonspastic tetraplegia following a spinal cord injury. He practiced using the device three times per week for four hours each session for more than 1,000 days. The research team administered standardized tests of upper-limb motor ability and functional participation to see how well the system improved his grip strength, quickness, and other basic skills.
Using this device improved the man’s upper-limb motor ability dramatically, according to several standardized tests. He improved his ability to grip and manipulate basic objects, and showed that he could perform ordinary tasks with his hands at the speed and dexterity levels of healthy individuals. He could move objects of different sizes and weights. With practice, he improved his ability to manipulate smaller household objects like a toothbrush or hairbrush. He also demonstrated that he could imagine different hand positions to proportionally adjust and control different hand movements.
“Our study demonstrated that patients with tetraplegia might be able to restore some of their skilled hand function with an implanted device that allows them to control movements with their own thoughts,” said Dr. Bockbrader. “Although this technology must be refined and tested before it can go from the laboratory to the public, it may one day offer people with disabilities a way to live and work more independently, and enable them to perform daily tasks.”
Concussion Recovery Varies Among Children
Not all children follow the same path to concussion recovery, nor do they have the same predictors for returning to normal activity, investigators reported. Their study also suggests that younger children should be considered separately from high-school students.
“Concussions are common among children, yet the literature is limited with regard to understanding trajectory of recovery after concussion, particularly in children with non-sports-related injuries and for younger children,” said Kaitlyn Chin, a second-year medical student at University of New England College of Osteopathic Medicine in Biddeford, Maine. “We were particularly interested in understanding how activity levels during recovery from concussion influence time to full recovery, to be able to identify modifiable factors to help guide concussion care. Previous studies have noted differences in the amount of time it takes children to recover from a concussion, and our team recently initiated a study to see if we can identify predictors associated with the amount of time between injury and when a child is medically cleared to return to activities which place the child at risk for reinjury.”
Ms. Chin’s team at Kennedy Krieger Institute in Baltimore reviewed the medical records of 178 children who were treated for concussions at an academically affiliated, rehabilitation-based clinic. The children had been medically cleared to return to play between September 2015 and February 2017. The children included in the study ranged in age from 6 to 17. A slight majority was younger than 14. Each child’s first visit to the clinic was within 60 days of his or her concussion.
The researchers reviewed each child’s record, noting when they had been approved to return to play. Then they looked at several other factors for each child, including sex, cause of the concussion (ie, sports or non-sports-related), number of symptoms, school attendance, and exercise status at the initial visit to the clinic. Finally, they considered these factors when the children were placed into two categories—children under 14 and children over 14—to examine potential differences related to age.
Ms. Chin’s team found that the number of symptoms affected how quickly all children were cleared to return to play. Fewer symptoms were associated with a faster return to play. For older children, male sex and higher level of exercise during recovery were associated with a faster return to play. For younger children, higher levels of exercise and school participation (eg, attending class and completing homework and tests) were associated with faster return to play.
Overall, this study shows that elementary and middle-school-aged children should be considered separately from high-school-aged students when considering risk factors for prolonged recovery from a concussion. Furthermore, Ms. Chin’s team found that school participation and exercise were not harmful and did not prolong recovery.
“Our study adds to the literature supporting that return to cognitive and safe physical activities while a child is still recovering from concussion does not prolong time to recovery,” said Ms. Chin. “Every child is different, and recovery is different for each concussion. [Therefore], a concussion recovery plan should be tailored for each child, and parents should seek help from the child’s pediatrician or other medical professionals for guiding care after a concussion.”
Medicine May Not Affect Concussion Recovery
Medications commonly prescribed to reduce symptoms of concussion may not affect recovery, said investigators. Sports medicine physicians commonly treat patients with concussion, so researchers in Utah investigated how some widely prescribed treatments might affect patients’ recovery.
“We really do not have much other than rest and gentle exercise to combat symptoms of concussion,” said Venessa Lee, MD, a physical medicine and rehabilitation resident at University of Utah Health in Salt Lake City. “Medications are commonly prescribed to help with symptoms, but there is little evidence that they help more than just time and rest.”
Although FDA has not approved any medication to treat concussion, physicians may prescribe medications like gabapentin or tricyclic antidepressants (TCAs) to help reduce symptoms during recovery. To examine whether these drugs benefit patients, Dr. Lee and her research team looked at 277 patients who had been diagnosed with concussion at a local academic sports medicine practice. At each of their visits to the clinic during recovery, patients reported their postconcussion symptoms. The research team used a score sheet to measure their symptoms, and they tracked scores of patients who had more than one visit to the clinic for as long as one year.
Patients were separated into three groups for the study: those not prescribed any medication, those prescribed gabapentin, and those prescribed one of two TCAs, amitriptyline or nortriptyline. Based on self-reported information, investigators gave each patient a score for two factors of postconcussion recovery: headaches and a combination of 22 symptoms, including headaches. Each score was on a scale of 0 to 6.
After they adjusted scores for gender and age, Dr. Lee’s team found that headache and combined symptoms scores decreased significantly within days after the first clinic visit for all three groups of patients—those who had taken no medications, those who had been prescribed gabapentin, and those who had been prescribed a TCA. Patients who had been prescribed any of the medications had significantly higher scores for headaches and overall postconcussion symptoms to begin with, but no one type of medication had any better or worse effect over the duration of the study.
“Patients’ symptoms improve with time after a concussion,” said Dr. Lee. “When we looked at [patients who received] gabapentin and TCAs, their symptoms improved over time as well, but similar to those that did not receive a medication.”
Based on this study, neither gabapentin nor TCAs appear to provide any additional benefit for postconcussion recovery. With this information, patients may be able to avoid taking unnecessary medications as they recover from concussions. Patients should speak with a physician about their symptoms after a concussion, said Dr. Lee.
“Though the two medications we studied did not show a profound improvement in our analysis, this was a retrospective study … which has many drawbacks and limitations. We need to do more research to really find the best method for improving postconcussive symptoms.”
Ballet Helps Children with Musculoskeletal and Neurologic Conditions
Adaptive ballet classes provide functional improvement and social interactions for children with musculoskeletal and neurologic conditions, according to researchers. This type of arts-based adaptive therapy is a promising expansion to successful adaptive sports therapies, said the investigators.
“While great strides have been made in adaptive sports, there are still relatively few opportunities in the arts for people with disabilities,” said Sarah Stauder, MD, a physician at the Medical College of Wisconsin in Milwaukee. “Because of this [scarcity], we wanted to evaluate the effect of adaptive ballet on the physical, emotional, social, and academic function of children with physical impairments. The program is a collaboration between a children’s hospital and a metropolitan ballet company that brings together professional dancers, pediatric doctors, physical and occupational therapists, and children with physical disabilities for a series of dance classes.”
The goal of the study was to see whether a weekly, 45-mintute ballet class with 15 minutes of ballet education over five consecutive weeks would improve the children’s balance, physical functions, social skills, and overall quality of life. Eighteen children (17 girls) from ages 5 to 14, took part in the class. Assessments of each child were performed before and after the series of classes using the Pediatric Quality of Life Inventory, the PEDI-CAT survey, and the Pediatric Balance Scale. Finally, a questionnaire was used to assess each child’s success in achieving individual goals set for the class.
At the end of the five weeks, 94% of participants reached their individual goals for the ballet program. PEDI-CAT scores improved after completion of the program, and the program was most beneficial to participants who had lower functioning and quality of life at the beginning of the program. Finally, the researchers noticed an average improvement in balance among the participants.
“Adaptive programs like the one studied here give children the opportunity to participate in activities they otherwise would have no way to do,” said Dr. Stauder. “More specifically, these dance classes instilled a sense of pride and confidence in the children while improving their physical functioning and quality of life. Our study should open the door to more arts-based therapy for children. It is an effective and enjoyable way for patients to get the therapy they need. When kids are active in an activity that interests them, they naturally make greater strides, and we were able to see this in their day-to-day function.”
Genetic Risk Score Predicts TBI Outcomes
A genetic risk score could help predict a patient’s quality of life after a traumatic brain injury (TBI), said researchers. One day, physicians could have a simple method to forecast a patient’s recovery and personalize therapy to maximize quality of life.
“Gene pathways can influence all of our biologic functions and risk for many health outcomes,” said Mark Linsenmeyer, MD, a resident physician at the University of Pittsburgh Medical Center. “Each person has a unique inherited genetic code. By studying one gene pathway in a large group of people with the same disease or health problem, we hope to unlock clues to why some people have different outcomes than others. This knowledge may be used to help physicians make the best treatment choice for each person.”
Dr. Linsenmeyer and colleagues set out to investigate how genes that affect the brain’s dopamine pathways could predict recovery in people with moderate-to-severe TBI. The team recruited 94 adults with TBI from a level-1 trauma center. They focused on the following five genes in the dopamine pathways: COMT rs4680, VMAT2 rs363226, DRD2 rs6279, ANKK1 Taq1a, and MAOA VNTR. They defined which risk genotypes were associated with lower average scores on surveys filled out by patients with TBI to describe their overall quality of life at six and 12 months after their injuries.
The researchers analyzed how individual variants of each of these five genes could affect patients’ quality of life, and then generated a weighted gene risk score as a measure to reflect cumulative risk represented by all genotypes included in the score. Based on available literature about dopamine pathway genetics, they predicted that their gene risk score calculation tool should be specific to a patient’s sex.
Before they calculated gene risk scores, the research team noticed that only COMT could significantly predict quality of life for a subset of patients six months after their injuries. After generating sex-specific gene risk scores, they found that variants of all five genes on the dopamine pathway could meaningfully contribute to a gene risk score that was highly predictive of quality of life after six months for patients of both sexes with TBI, and also predictive of quality of life after one year for women.
Electrical Stimulation Device Improves Motor Function
A person with a spinal cord injury can improve his or her ability to grip and move household objects by using an electrical stimulation device controlled by his or her thoughts, according to researchers. The study suggests that this new technology could one day enhance quality of life among people with disabilities and allow them to live more independently.
People with tetraplegia lose upper-limb strength and dexterity, which has a severe impact on their independence and quality of life. New technology that connects a person’s brain to an implanted functional electrical stimulation orthotics device on the hands could restore manual dexterity and grip strength, thus allowing him or her to perform simple daily tasks like holding a toothbrush without help.
“Individuals with cervical spinal cord injury identify recovery of the use of their hands as the single most impactful way that neurotechnology could change their lives,” said Marcie Bockbrader, MD, PhD, Assistant Professor of Physical Medicine and Rehabilitation at the Ohio State University Wexner Medical Center in Columbus. “Giving a person back [his or her] hands reduces dependence on others. It makes it possible to do the little things—like cutting food or opening a door—that are so essential to being able to take care of oneself.”
To test how well this thought-controlled brain–computer interface system works in real life to improve hand strength and dexterity, Dr. Bockbrader and her research team surgically implanted one of these devices into the hand of a 26-year-old man with C5-level, nonspastic tetraplegia following a spinal cord injury. He practiced using the device three times per week for four hours each session for more than 1,000 days. The research team administered standardized tests of upper-limb motor ability and functional participation to see how well the system improved his grip strength, quickness, and other basic skills.
Using this device improved the man’s upper-limb motor ability dramatically, according to several standardized tests. He improved his ability to grip and manipulate basic objects, and showed that he could perform ordinary tasks with his hands at the speed and dexterity levels of healthy individuals. He could move objects of different sizes and weights. With practice, he improved his ability to manipulate smaller household objects like a toothbrush or hairbrush. He also demonstrated that he could imagine different hand positions to proportionally adjust and control different hand movements.
“Our study demonstrated that patients with tetraplegia might be able to restore some of their skilled hand function with an implanted device that allows them to control movements with their own thoughts,” said Dr. Bockbrader. “Although this technology must be refined and tested before it can go from the laboratory to the public, it may one day offer people with disabilities a way to live and work more independently, and enable them to perform daily tasks.”
Concussion Recovery Varies Among Children
Not all children follow the same path to concussion recovery, nor do they have the same predictors for returning to normal activity, investigators reported. Their study also suggests that younger children should be considered separately from high-school students.
“Concussions are common among children, yet the literature is limited with regard to understanding trajectory of recovery after concussion, particularly in children with non-sports-related injuries and for younger children,” said Kaitlyn Chin, a second-year medical student at University of New England College of Osteopathic Medicine in Biddeford, Maine. “We were particularly interested in understanding how activity levels during recovery from concussion influence time to full recovery, to be able to identify modifiable factors to help guide concussion care. Previous studies have noted differences in the amount of time it takes children to recover from a concussion, and our team recently initiated a study to see if we can identify predictors associated with the amount of time between injury and when a child is medically cleared to return to activities which place the child at risk for reinjury.”
Ms. Chin’s team at Kennedy Krieger Institute in Baltimore reviewed the medical records of 178 children who were treated for concussions at an academically affiliated, rehabilitation-based clinic. The children had been medically cleared to return to play between September 2015 and February 2017. The children included in the study ranged in age from 6 to 17. A slight majority was younger than 14. Each child’s first visit to the clinic was within 60 days of his or her concussion.
The researchers reviewed each child’s record, noting when they had been approved to return to play. Then they looked at several other factors for each child, including sex, cause of the concussion (ie, sports or non-sports-related), number of symptoms, school attendance, and exercise status at the initial visit to the clinic. Finally, they considered these factors when the children were placed into two categories—children under 14 and children over 14—to examine potential differences related to age.
Ms. Chin’s team found that the number of symptoms affected how quickly all children were cleared to return to play. Fewer symptoms were associated with a faster return to play. For older children, male sex and higher level of exercise during recovery were associated with a faster return to play. For younger children, higher levels of exercise and school participation (eg, attending class and completing homework and tests) were associated with faster return to play.
Overall, this study shows that elementary and middle-school-aged children should be considered separately from high-school-aged students when considering risk factors for prolonged recovery from a concussion. Furthermore, Ms. Chin’s team found that school participation and exercise were not harmful and did not prolong recovery.
“Our study adds to the literature supporting that return to cognitive and safe physical activities while a child is still recovering from concussion does not prolong time to recovery,” said Ms. Chin. “Every child is different, and recovery is different for each concussion. [Therefore], a concussion recovery plan should be tailored for each child, and parents should seek help from the child’s pediatrician or other medical professionals for guiding care after a concussion.”
Medicine May Not Affect Concussion Recovery
Medications commonly prescribed to reduce symptoms of concussion may not affect recovery, said investigators. Sports medicine physicians commonly treat patients with concussion, so researchers in Utah investigated how some widely prescribed treatments might affect patients’ recovery.
“We really do not have much other than rest and gentle exercise to combat symptoms of concussion,” said Venessa Lee, MD, a physical medicine and rehabilitation resident at University of Utah Health in Salt Lake City. “Medications are commonly prescribed to help with symptoms, but there is little evidence that they help more than just time and rest.”
Although FDA has not approved any medication to treat concussion, physicians may prescribe medications like gabapentin or tricyclic antidepressants (TCAs) to help reduce symptoms during recovery. To examine whether these drugs benefit patients, Dr. Lee and her research team looked at 277 patients who had been diagnosed with concussion at a local academic sports medicine practice. At each of their visits to the clinic during recovery, patients reported their postconcussion symptoms. The research team used a score sheet to measure their symptoms, and they tracked scores of patients who had more than one visit to the clinic for as long as one year.
Patients were separated into three groups for the study: those not prescribed any medication, those prescribed gabapentin, and those prescribed one of two TCAs, amitriptyline or nortriptyline. Based on self-reported information, investigators gave each patient a score for two factors of postconcussion recovery: headaches and a combination of 22 symptoms, including headaches. Each score was on a scale of 0 to 6.
After they adjusted scores for gender and age, Dr. Lee’s team found that headache and combined symptoms scores decreased significantly within days after the first clinic visit for all three groups of patients—those who had taken no medications, those who had been prescribed gabapentin, and those who had been prescribed a TCA. Patients who had been prescribed any of the medications had significantly higher scores for headaches and overall postconcussion symptoms to begin with, but no one type of medication had any better or worse effect over the duration of the study.
“Patients’ symptoms improve with time after a concussion,” said Dr. Lee. “When we looked at [patients who received] gabapentin and TCAs, their symptoms improved over time as well, but similar to those that did not receive a medication.”
Based on this study, neither gabapentin nor TCAs appear to provide any additional benefit for postconcussion recovery. With this information, patients may be able to avoid taking unnecessary medications as they recover from concussions. Patients should speak with a physician about their symptoms after a concussion, said Dr. Lee.
“Though the two medications we studied did not show a profound improvement in our analysis, this was a retrospective study … which has many drawbacks and limitations. We need to do more research to really find the best method for improving postconcussive symptoms.”
Ballet Helps Children with Musculoskeletal and Neurologic Conditions
Adaptive ballet classes provide functional improvement and social interactions for children with musculoskeletal and neurologic conditions, according to researchers. This type of arts-based adaptive therapy is a promising expansion to successful adaptive sports therapies, said the investigators.
“While great strides have been made in adaptive sports, there are still relatively few opportunities in the arts for people with disabilities,” said Sarah Stauder, MD, a physician at the Medical College of Wisconsin in Milwaukee. “Because of this [scarcity], we wanted to evaluate the effect of adaptive ballet on the physical, emotional, social, and academic function of children with physical impairments. The program is a collaboration between a children’s hospital and a metropolitan ballet company that brings together professional dancers, pediatric doctors, physical and occupational therapists, and children with physical disabilities for a series of dance classes.”
The goal of the study was to see whether a weekly, 45-mintute ballet class with 15 minutes of ballet education over five consecutive weeks would improve the children’s balance, physical functions, social skills, and overall quality of life. Eighteen children (17 girls) from ages 5 to 14, took part in the class. Assessments of each child were performed before and after the series of classes using the Pediatric Quality of Life Inventory, the PEDI-CAT survey, and the Pediatric Balance Scale. Finally, a questionnaire was used to assess each child’s success in achieving individual goals set for the class.
At the end of the five weeks, 94% of participants reached their individual goals for the ballet program. PEDI-CAT scores improved after completion of the program, and the program was most beneficial to participants who had lower functioning and quality of life at the beginning of the program. Finally, the researchers noticed an average improvement in balance among the participants.
“Adaptive programs like the one studied here give children the opportunity to participate in activities they otherwise would have no way to do,” said Dr. Stauder. “More specifically, these dance classes instilled a sense of pride and confidence in the children while improving their physical functioning and quality of life. Our study should open the door to more arts-based therapy for children. It is an effective and enjoyable way for patients to get the therapy they need. When kids are active in an activity that interests them, they naturally make greater strides, and we were able to see this in their day-to-day function.”
Genetic Risk Score Predicts TBI Outcomes
A genetic risk score could help predict a patient’s quality of life after a traumatic brain injury (TBI), said researchers. One day, physicians could have a simple method to forecast a patient’s recovery and personalize therapy to maximize quality of life.
“Gene pathways can influence all of our biologic functions and risk for many health outcomes,” said Mark Linsenmeyer, MD, a resident physician at the University of Pittsburgh Medical Center. “Each person has a unique inherited genetic code. By studying one gene pathway in a large group of people with the same disease or health problem, we hope to unlock clues to why some people have different outcomes than others. This knowledge may be used to help physicians make the best treatment choice for each person.”
Dr. Linsenmeyer and colleagues set out to investigate how genes that affect the brain’s dopamine pathways could predict recovery in people with moderate-to-severe TBI. The team recruited 94 adults with TBI from a level-1 trauma center. They focused on the following five genes in the dopamine pathways: COMT rs4680, VMAT2 rs363226, DRD2 rs6279, ANKK1 Taq1a, and MAOA VNTR. They defined which risk genotypes were associated with lower average scores on surveys filled out by patients with TBI to describe their overall quality of life at six and 12 months after their injuries.
The researchers analyzed how individual variants of each of these five genes could affect patients’ quality of life, and then generated a weighted gene risk score as a measure to reflect cumulative risk represented by all genotypes included in the score. Based on available literature about dopamine pathway genetics, they predicted that their gene risk score calculation tool should be specific to a patient’s sex.
Before they calculated gene risk scores, the research team noticed that only COMT could significantly predict quality of life for a subset of patients six months after their injuries. After generating sex-specific gene risk scores, they found that variants of all five genes on the dopamine pathway could meaningfully contribute to a gene risk score that was highly predictive of quality of life after six months for patients of both sexes with TBI, and also predictive of quality of life after one year for women.
Advances Broaden Treatment Options for Parkinson’s Disease Motor Symptoms
NAPLES, FL—Although levodopa remains the standard treatment for managing motor symptoms in patients with Parkinson’s disease, many new options are available, and others are in the pipeline. These options include novel modes of carbidopa–levodopa delivery, new adjunctive medications, and innovations in deep brain stimulation (DBS) therapy. 
“The explosion of different therapies for Parkinson’s disease is quite exciting,” said Stanley P. Fisher, MD, at the 45thAnnual Meeting of the Southern Clinical Neurological Society. “However, the key is to address individualized management considerations, such as age, cognitive/psychiatric profile, and caregiver status.” Dr. Fisher is Codirector of Saint Luke’s Marion Bloch Neuroscience Institute and Associate Professor of Neurology at the University of Missouri in Kansas City.
Clinical factors to consider include fluctuations in symptom control as the disease progresses—specifically, wearing off (ie, re-emergence of symptoms prior to the next scheduled levodopa dose), on and off time (ie, unpredictable periods of good or poor symptom control), delayed on response (ie, dose takes longer to improve symptoms than previously), dose failure, and levodopa-induced dyskinesia, Dr. Fisher noted. Risk factors for developing dyskinesia include increasing doses of levodopa beyond 400 mg, female gender, low body weight, and earlier age of Parkinson’s disease onset, independent of how many years a patient has been taking levodopa.
Levodopa Preparations
“Levodopa has been used to treat Parkinson’s disease since the early ’70s, and its efficacy is well established,” Dr. Fisher said. “There has been an attempt over the years to create a perfect long-lasting levodopa.” In 1988, the FDA approved Sinemet, an immediate-release combination carbidopa–levodopa oral treatment. Carbidopa prevents the breakdown of levodopa before it crosses the blood–brain barrier, allowing lower doses of levodopa to be used. Sinemet CR (controlled release) has an unpredictable time of onset, Dr. Fisher said. “It should not be used during the day. But it may be helpful to prescribe this drug for use at night, when the time of onset is not critical.”
Parcopa, a carbidopa–levodopa preparation in the form of orally disintegrating tablets, was approved in 2004. “Clinically, it is not much different from Sinemet,” Dr. Fisher said. “However, it is expensive and should be used strictly by people who have difficulty swallowing.”
Duopa, which was approved in 2015, is a carbidopa–levodopa enteral solution delivered by a programmable pump via a transgastric jejunal tube. “It is an intestinal gel that is delivered continuously for at least 16 hours a day,” Dr. Fisher said. “The treatment effect tends to wear off at night, so if the patient does not have a caregiver to help them with the early morning akinesia, using this drug may be quite difficult.”
Rytary is a carbidopa–levodopa extended-release capsule approved in 2015. “The capsules have different beads that allow immediate, intermediate, and long-term release of levodopa, with a half-life of about five hours,” Dr. Fisher said. “Issues related to delayed on and lack of peak-dose effect have limited its widespread use. In addition, the dosing conversion from Sinemet is not intuitive.”
Phase III study results are anticipated for the experimental drug ND0612, a novel liquid carbidopa–levodopa formulation for subcutaneous administration via a pump patch. In a randomized double-blind placebo-controlled parallel group study, investigators are assessing a high dose and a low dose of ND0612 as adjunctive treatment to oral levodopa. Previous research had shown greater bioavailability of the drug with subcutaneous versus oral administration. One study found significantly reduced off time with treatment, with 42% of patients having no off time, Dr. Fisher said.
An inhaled levodopa, CVT-301 (Inbrija), has been submitted to the FDA. The treatment’s novel inhalation system “requires the patient to have intact pulmonary function and certain manual skills. It also requires that oral carbidopa be taken separately,” Dr. Fisher added.
Adjunctive Therapy
“When we started using dopamine agonists and other levodopa-sparing therapies in 1999, it changed the way we treat Parkinson’s disease,” Dr. Fisher said. “Generally, these agents are not as effective as levodopa and potentially have more adverse effects. However, there are some patients with tremor-dominant disease who may respond to dopamine agonists better than to levodopa. Also, for younger patients on 300 mg of levodopa who are not well controlled, prescribing additional dopamine agonists may be the way to go.”
Approved by the FDA in 2004, subcutaneous apomorphine (a non-ergoline dopamine agonist) is delivered via injector pen. Another mode of apomorphine delivery—infusion via injection pump—has been available in Europe for more than 25 years and is being assessed for use in the US. Studies have found that apomorphine infusion may significantly reduce off time and increase on time. The most common adverse effect was skin nodules at the infusion site. In addition, sublingual apomorphine has been studied in a phase III trial and may be available soon, Dr. Fisher said.
Safinamide (Xydago) is a monoamine oxidase type B inhibitor approved in March 2017 indicated for patients who experience off episodes. “While I do not see any dramatic benefit of using this drug, it has two-year data to show that it is safe and effective,” Dr. Fisher noted.
Immediate-release amantadine, an N-methyl-D-aspartate antagonist, has been used to treat Parkinson’s disease since 2003. However, its treatment effect is not well sustained, and multiple doses of the drug throughout the day are not well tolerated, Dr. Fisher said. Extended-release amantadine (Gocovri), approved in August 2017, confers a significant reduction in the Unified Parkinson’s Disease Rating Scale score when given at night. Adverse effects include dizziness, edema, and orthostatic hypotension. “Hallucination is particularly a problem in patients older than 65,” Dr. Fisher said. “The good news is that 57% of hallucination problems resolve within two weeks as patients adjust to the medication. So, it may be worth giving it a try.”
Deep Brain Stimulation
Approved in 2002, the implantable Activa DBS system by Medtronic is indicated for idiopathic Parkinson’s disease of at least four years’ duration in patients who have disabling motor symptoms despite being on an optimized medication regimen but continue, even if briefly, to respond to levodopa, Dr. Fisher said. Used as adjunctive therapy, it provides bilateral stimulation of the internal globus pallidus or the subthalamic nucleus. In one study, patients had significant improvements in on and off time after six months of surgery.
Similar benefits were found for the St. Jude Medical Infinity DBS system, which was approved by the FDA in 2015. The system includes directional lead technology designed to allow physicians to precisely steer current towards the desired structural areas, thereby maximizing symptom management and potentially reducing adverse effects.
The newest DBS system on the market is the Vercise system by Boston Scientific. “This is the only platform that allows independent current delivery to each of the 16 electrodes on the implanted leads,” Dr. Fisher said. “The rechargeable system has a battery life of more than 15 years.” Although the technology has been available in Europe for the last five years, the Vercise system was approved for use in the US in December 2017. Its approval was based on the results of the INTREPID study, the first multicenter, prospective, double-blind, randomized sham-controlled study of DBS for Parkinson’s disease in the US.
“The technology is truly amazing,” Dr. Fisher said. “How the systemperforms in clinical practice remains to be seen.”
—Adriene Marshall
Suggested Reading
Borgohain R, Szasz J, Stanzione P, et al. Randomized trial of safinamide add-on to levodopa in Parkinson’s disease with motor fluctuations. Mov Disord. 2014;29(2):229-237.
Fahn S, Oakes D, Shoulson I, et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med. 2004;351(24):2498-2508.
Hely MA, Morris JG, Reid WG, Trafficante R. Sydney Multicenter Study of Parkinson’s disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord. 2005;20(2):190-199.
Pahwa R, Tanner CM, Hauser RA, et al. ADS-5102 (Amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson disease (EASE LID Study): a randomized clinical trial. JAMA Neurol. 2017;74(8):941-949.
Schuepbach WM, Rau J, Knudsen K, et al. Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med. 2013;368(7):610-622.
NAPLES, FL—Although levodopa remains the standard treatment for managing motor symptoms in patients with Parkinson’s disease, many new options are available, and others are in the pipeline. These options include novel modes of carbidopa–levodopa delivery, new adjunctive medications, and innovations in deep brain stimulation (DBS) therapy.
“The explosion of different therapies for Parkinson’s disease is quite exciting,” said Stanley P. Fisher, MD, at the 45thAnnual Meeting of the Southern Clinical Neurological Society. “However, the key is to address individualized management considerations, such as age, cognitive/psychiatric profile, and caregiver status.” Dr. Fisher is Codirector of Saint Luke’s Marion Bloch Neuroscience Institute and Associate Professor of Neurology at the University of Missouri in Kansas City.
Clinical factors to consider include fluctuations in symptom control as the disease progresses—specifically, wearing off (ie, re-emergence of symptoms prior to the next scheduled levodopa dose), on and off time (ie, unpredictable periods of good or poor symptom control), delayed on response (ie, dose takes longer to improve symptoms than previously), dose failure, and levodopa-induced dyskinesia, Dr. Fisher noted. Risk factors for developing dyskinesia include increasing doses of levodopa beyond 400 mg, female gender, low body weight, and earlier age of Parkinson’s disease onset, independent of how many years a patient has been taking levodopa.
Levodopa Preparations
“Levodopa has been used to treat Parkinson’s disease since the early ’70s, and its efficacy is well established,” Dr. Fisher said. “There has been an attempt over the years to create a perfect long-lasting levodopa.” In 1988, the FDA approved Sinemet, an immediate-release combination carbidopa–levodopa oral treatment. Carbidopa prevents the breakdown of levodopa before it crosses the blood–brain barrier, allowing lower doses of levodopa to be used. Sinemet CR (controlled release) has an unpredictable time of onset, Dr. Fisher said. “It should not be used during the day. But it may be helpful to prescribe this drug for use at night, when the time of onset is not critical.”
Parcopa, a carbidopa–levodopa preparation in the form of orally disintegrating tablets, was approved in 2004. “Clinically, it is not much different from Sinemet,” Dr. Fisher said. “However, it is expensive and should be used strictly by people who have difficulty swallowing.”
Duopa, which was approved in 2015, is a carbidopa–levodopa enteral solution delivered by a programmable pump via a transgastric jejunal tube. “It is an intestinal gel that is delivered continuously for at least 16 hours a day,” Dr. Fisher said. “The treatment effect tends to wear off at night, so if the patient does not have a caregiver to help them with the early morning akinesia, using this drug may be quite difficult.”
Rytary is a carbidopa–levodopa extended-release capsule approved in 2015. “The capsules have different beads that allow immediate, intermediate, and long-term release of levodopa, with a half-life of about five hours,” Dr. Fisher said. “Issues related to delayed on and lack of peak-dose effect have limited its widespread use. In addition, the dosing conversion from Sinemet is not intuitive.”
Phase III study results are anticipated for the experimental drug ND0612, a novel liquid carbidopa–levodopa formulation for subcutaneous administration via a pump patch. In a randomized double-blind placebo-controlled parallel group study, investigators are assessing a high dose and a low dose of ND0612 as adjunctive treatment to oral levodopa. Previous research had shown greater bioavailability of the drug with subcutaneous versus oral administration. One study found significantly reduced off time with treatment, with 42% of patients having no off time, Dr. Fisher said.
An inhaled levodopa, CVT-301 (Inbrija), has been submitted to the FDA. The treatment’s novel inhalation system “requires the patient to have intact pulmonary function and certain manual skills. It also requires that oral carbidopa be taken separately,” Dr. Fisher added.
Adjunctive Therapy
“When we started using dopamine agonists and other levodopa-sparing therapies in 1999, it changed the way we treat Parkinson’s disease,” Dr. Fisher said. “Generally, these agents are not as effective as levodopa and potentially have more adverse effects. However, there are some patients with tremor-dominant disease who may respond to dopamine agonists better than to levodopa. Also, for younger patients on 300 mg of levodopa who are not well controlled, prescribing additional dopamine agonists may be the way to go.”
Approved by the FDA in 2004, subcutaneous apomorphine (a non-ergoline dopamine agonist) is delivered via injector pen. Another mode of apomorphine delivery—infusion via injection pump—has been available in Europe for more than 25 years and is being assessed for use in the US. Studies have found that apomorphine infusion may significantly reduce off time and increase on time. The most common adverse effect was skin nodules at the infusion site. In addition, sublingual apomorphine has been studied in a phase III trial and may be available soon, Dr. Fisher said.
Safinamide (Xydago) is a monoamine oxidase type B inhibitor approved in March 2017 indicated for patients who experience off episodes. “While I do not see any dramatic benefit of using this drug, it has two-year data to show that it is safe and effective,” Dr. Fisher noted.
Immediate-release amantadine, an N-methyl-D-aspartate antagonist, has been used to treat Parkinson’s disease since 2003. However, its treatment effect is not well sustained, and multiple doses of the drug throughout the day are not well tolerated, Dr. Fisher said. Extended-release amantadine (Gocovri), approved in August 2017, confers a significant reduction in the Unified Parkinson’s Disease Rating Scale score when given at night. Adverse effects include dizziness, edema, and orthostatic hypotension. “Hallucination is particularly a problem in patients older than 65,” Dr. Fisher said. “The good news is that 57% of hallucination problems resolve within two weeks as patients adjust to the medication. So, it may be worth giving it a try.”
Deep Brain Stimulation
Approved in 2002, the implantable Activa DBS system by Medtronic is indicated for idiopathic Parkinson’s disease of at least four years’ duration in patients who have disabling motor symptoms despite being on an optimized medication regimen but continue, even if briefly, to respond to levodopa, Dr. Fisher said. Used as adjunctive therapy, it provides bilateral stimulation of the internal globus pallidus or the subthalamic nucleus. In one study, patients had significant improvements in on and off time after six months of surgery.
Similar benefits were found for the St. Jude Medical Infinity DBS system, which was approved by the FDA in 2015. The system includes directional lead technology designed to allow physicians to precisely steer current towards the desired structural areas, thereby maximizing symptom management and potentially reducing adverse effects.
The newest DBS system on the market is the Vercise system by Boston Scientific. “This is the only platform that allows independent current delivery to each of the 16 electrodes on the implanted leads,” Dr. Fisher said. “The rechargeable system has a battery life of more than 15 years.” Although the technology has been available in Europe for the last five years, the Vercise system was approved for use in the US in December 2017. Its approval was based on the results of the INTREPID study, the first multicenter, prospective, double-blind, randomized sham-controlled study of DBS for Parkinson’s disease in the US.
“The technology is truly amazing,” Dr. Fisher said. “How the systemperforms in clinical practice remains to be seen.”
—Adriene Marshall
Suggested Reading
Borgohain R, Szasz J, Stanzione P, et al. Randomized trial of safinamide add-on to levodopa in Parkinson’s disease with motor fluctuations. Mov Disord. 2014;29(2):229-237.
Fahn S, Oakes D, Shoulson I, et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med. 2004;351(24):2498-2508.
Hely MA, Morris JG, Reid WG, Trafficante R. Sydney Multicenter Study of Parkinson’s disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord. 2005;20(2):190-199.
Pahwa R, Tanner CM, Hauser RA, et al. ADS-5102 (Amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson disease (EASE LID Study): a randomized clinical trial. JAMA Neurol. 2017;74(8):941-949.
Schuepbach WM, Rau J, Knudsen K, et al. Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med. 2013;368(7):610-622.
NAPLES, FL—Although levodopa remains the standard treatment for managing motor symptoms in patients with Parkinson’s disease, many new options are available, and others are in the pipeline. These options include novel modes of carbidopa–levodopa delivery, new adjunctive medications, and innovations in deep brain stimulation (DBS) therapy.
“The explosion of different therapies for Parkinson’s disease is quite exciting,” said Stanley P. Fisher, MD, at the 45thAnnual Meeting of the Southern Clinical Neurological Society. “However, the key is to address individualized management considerations, such as age, cognitive/psychiatric profile, and caregiver status.” Dr. Fisher is Codirector of Saint Luke’s Marion Bloch Neuroscience Institute and Associate Professor of Neurology at the University of Missouri in Kansas City.
Clinical factors to consider include fluctuations in symptom control as the disease progresses—specifically, wearing off (ie, re-emergence of symptoms prior to the next scheduled levodopa dose), on and off time (ie, unpredictable periods of good or poor symptom control), delayed on response (ie, dose takes longer to improve symptoms than previously), dose failure, and levodopa-induced dyskinesia, Dr. Fisher noted. Risk factors for developing dyskinesia include increasing doses of levodopa beyond 400 mg, female gender, low body weight, and earlier age of Parkinson’s disease onset, independent of how many years a patient has been taking levodopa.
Levodopa Preparations
“Levodopa has been used to treat Parkinson’s disease since the early ’70s, and its efficacy is well established,” Dr. Fisher said. “There has been an attempt over the years to create a perfect long-lasting levodopa.” In 1988, the FDA approved Sinemet, an immediate-release combination carbidopa–levodopa oral treatment. Carbidopa prevents the breakdown of levodopa before it crosses the blood–brain barrier, allowing lower doses of levodopa to be used. Sinemet CR (controlled release) has an unpredictable time of onset, Dr. Fisher said. “It should not be used during the day. But it may be helpful to prescribe this drug for use at night, when the time of onset is not critical.”
Parcopa, a carbidopa–levodopa preparation in the form of orally disintegrating tablets, was approved in 2004. “Clinically, it is not much different from Sinemet,” Dr. Fisher said. “However, it is expensive and should be used strictly by people who have difficulty swallowing.”
Duopa, which was approved in 2015, is a carbidopa–levodopa enteral solution delivered by a programmable pump via a transgastric jejunal tube. “It is an intestinal gel that is delivered continuously for at least 16 hours a day,” Dr. Fisher said. “The treatment effect tends to wear off at night, so if the patient does not have a caregiver to help them with the early morning akinesia, using this drug may be quite difficult.”
Rytary is a carbidopa–levodopa extended-release capsule approved in 2015. “The capsules have different beads that allow immediate, intermediate, and long-term release of levodopa, with a half-life of about five hours,” Dr. Fisher said. “Issues related to delayed on and lack of peak-dose effect have limited its widespread use. In addition, the dosing conversion from Sinemet is not intuitive.”
Phase III study results are anticipated for the experimental drug ND0612, a novel liquid carbidopa–levodopa formulation for subcutaneous administration via a pump patch. In a randomized double-blind placebo-controlled parallel group study, investigators are assessing a high dose and a low dose of ND0612 as adjunctive treatment to oral levodopa. Previous research had shown greater bioavailability of the drug with subcutaneous versus oral administration. One study found significantly reduced off time with treatment, with 42% of patients having no off time, Dr. Fisher said.
An inhaled levodopa, CVT-301 (Inbrija), has been submitted to the FDA. The treatment’s novel inhalation system “requires the patient to have intact pulmonary function and certain manual skills. It also requires that oral carbidopa be taken separately,” Dr. Fisher added.
Adjunctive Therapy
“When we started using dopamine agonists and other levodopa-sparing therapies in 1999, it changed the way we treat Parkinson’s disease,” Dr. Fisher said. “Generally, these agents are not as effective as levodopa and potentially have more adverse effects. However, there are some patients with tremor-dominant disease who may respond to dopamine agonists better than to levodopa. Also, for younger patients on 300 mg of levodopa who are not well controlled, prescribing additional dopamine agonists may be the way to go.”
Approved by the FDA in 2004, subcutaneous apomorphine (a non-ergoline dopamine agonist) is delivered via injector pen. Another mode of apomorphine delivery—infusion via injection pump—has been available in Europe for more than 25 years and is being assessed for use in the US. Studies have found that apomorphine infusion may significantly reduce off time and increase on time. The most common adverse effect was skin nodules at the infusion site. In addition, sublingual apomorphine has been studied in a phase III trial and may be available soon, Dr. Fisher said.
Safinamide (Xydago) is a monoamine oxidase type B inhibitor approved in March 2017 indicated for patients who experience off episodes. “While I do not see any dramatic benefit of using this drug, it has two-year data to show that it is safe and effective,” Dr. Fisher noted.
Immediate-release amantadine, an N-methyl-D-aspartate antagonist, has been used to treat Parkinson’s disease since 2003. However, its treatment effect is not well sustained, and multiple doses of the drug throughout the day are not well tolerated, Dr. Fisher said. Extended-release amantadine (Gocovri), approved in August 2017, confers a significant reduction in the Unified Parkinson’s Disease Rating Scale score when given at night. Adverse effects include dizziness, edema, and orthostatic hypotension. “Hallucination is particularly a problem in patients older than 65,” Dr. Fisher said. “The good news is that 57% of hallucination problems resolve within two weeks as patients adjust to the medication. So, it may be worth giving it a try.”
Deep Brain Stimulation
Approved in 2002, the implantable Activa DBS system by Medtronic is indicated for idiopathic Parkinson’s disease of at least four years’ duration in patients who have disabling motor symptoms despite being on an optimized medication regimen but continue, even if briefly, to respond to levodopa, Dr. Fisher said. Used as adjunctive therapy, it provides bilateral stimulation of the internal globus pallidus or the subthalamic nucleus. In one study, patients had significant improvements in on and off time after six months of surgery.
Similar benefits were found for the St. Jude Medical Infinity DBS system, which was approved by the FDA in 2015. The system includes directional lead technology designed to allow physicians to precisely steer current towards the desired structural areas, thereby maximizing symptom management and potentially reducing adverse effects.
The newest DBS system on the market is the Vercise system by Boston Scientific. “This is the only platform that allows independent current delivery to each of the 16 electrodes on the implanted leads,” Dr. Fisher said. “The rechargeable system has a battery life of more than 15 years.” Although the technology has been available in Europe for the last five years, the Vercise system was approved for use in the US in December 2017. Its approval was based on the results of the INTREPID study, the first multicenter, prospective, double-blind, randomized sham-controlled study of DBS for Parkinson’s disease in the US.
“The technology is truly amazing,” Dr. Fisher said. “How the systemperforms in clinical practice remains to be seen.”
—Adriene Marshall
Suggested Reading
Borgohain R, Szasz J, Stanzione P, et al. Randomized trial of safinamide add-on to levodopa in Parkinson’s disease with motor fluctuations. Mov Disord. 2014;29(2):229-237.
Fahn S, Oakes D, Shoulson I, et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med. 2004;351(24):2498-2508.
Hely MA, Morris JG, Reid WG, Trafficante R. Sydney Multicenter Study of Parkinson’s disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord. 2005;20(2):190-199.
Pahwa R, Tanner CM, Hauser RA, et al. ADS-5102 (Amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson disease (EASE LID Study): a randomized clinical trial. JAMA Neurol. 2017;74(8):941-949.
Schuepbach WM, Rau J, Knudsen K, et al. Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med. 2013;368(7):610-622.
How Are Newer DMTs Used in Pediatric MS?
SAN DIEGO—Newer oral and IV disease-modifying therapies (DMTs) for multiple sclerosis (MS) increasingly are used in children, according to data presented at the ACTRIMS 2018 Forum. These DMTs often are second-line therapies, but some patients receive them as first-line treatment.
“Newer DMTs … are being started more often over time at clinics participating in the US Network of Pediatric MS Centers,” said Kristen M. Krysko, MD, Clinical Fellow at the University of California, San Francisco School of Medicine, and colleagues. 
The short-term side effect profile of newer DMTs in children is similar to that in adults. The study may have underestimated side effects, however, and long-term safety data are lacking, the researchers noted.
Treatment Challenges
About 5% of patients with MS develop symptoms before age 18. “Treatment of pediatric MS is challenging, given high relapse rates and the lack of safety and efficacy data for DMTs in children,” Dr. Krysko and colleagues said. “Conventionally, first-line treatments for pediatric MS include interferon beta and glatiramer acetate, but these agents may be poorly tolerated, since they are given by injection, and may not adequately control the disease. Those with breakthrough events require escalation to more potent agents, which are increasingly used off-label in pediatric MS despite limited data about safety or efficacy in children.”
To characterize the use and safety of newer DMTs in children with MS and clinically isolated syndrome (CIS), Dr. Krysko and colleagues conducted a retrospective cohort study of prospectively collected data at 12 clinics participating in the US Network of Pediatric MS Centers as of August 2017.
The researchers examined patterns of newer DMT use and newer DMT side effects. They classified DMTs as injectable (ie, glatiramer acetate and beta-interferons), oral (ie, dimethyl fumarate, fingolimod, and teriflunomide), or IV (ie, natalizumab, rituximab, alemtuzumab, and ocrelizumab). The researchers considered dimethyl fumarate, fingolimod, teriflunomide, natalizumab, rituximab, ocrelizumab, alemtuzumab, and daclizumab to be newer therapies.
The cohort included more than 1,000 patients with MS or CIS. In all, 618 patients had received a DMT before age 18 (587 patients with a diagnosis of MS at last follow-up and 31 patients with a diagnosis of CIS at last follow-up). About 66% were female, and patients’ mean age at MS onset was approximately 13.
The Use of Oral and IV DMTs
From 2008 to 2017, use of newer oral and IV DMTs increased overall and as first-line therapy in patients younger than 12 and in patients 12 or older. Of the 618 patients who received a DMT before age 18, 259 (42%) received a newer DMT, and 104 (17%) received a newer DMT as a first-line therapy.
Newer DMTs used in patients before age 18 included natalizumab in 101 patients, dimethyl fumarate in 100 patients, rituximab in 57 patients, fingolimod in 37 patients, daclizumab in five patients, and teriflunomide in three patients. Newer DMTs used as first-line therapy in patients before age 18 included dimethyl fumarate in 36 patients, natalizumab in 30 patients, rituximab in 22 patients, fingolimod in 14 patients, and teriflunomide in two patients.
Patients were exposed to dimethyl fumarate for 149 person-years, natalizumab for 140 person-years, rituximab for 75 person-years, fingolimod for 55 person-years, daclizumab for 10 person-years, and teriflunomide for one person-year.
Randomized controlled trials of the efficacy of DMTs in children with MS are ongoing. Future studies may explore predictors of newer DMT use in children with MS, the researchers said.
—Jake Remaly
SAN DIEGO—Newer oral and IV disease-modifying therapies (DMTs) for multiple sclerosis (MS) increasingly are used in children, according to data presented at the ACTRIMS 2018 Forum. These DMTs often are second-line therapies, but some patients receive them as first-line treatment.
“Newer DMTs … are being started more often over time at clinics participating in the US Network of Pediatric MS Centers,” said Kristen M. Krysko, MD, Clinical Fellow at the University of California, San Francisco School of Medicine, and colleagues.
The short-term side effect profile of newer DMTs in children is similar to that in adults. The study may have underestimated side effects, however, and long-term safety data are lacking, the researchers noted.
Treatment Challenges
About 5% of patients with MS develop symptoms before age 18. “Treatment of pediatric MS is challenging, given high relapse rates and the lack of safety and efficacy data for DMTs in children,” Dr. Krysko and colleagues said. “Conventionally, first-line treatments for pediatric MS include interferon beta and glatiramer acetate, but these agents may be poorly tolerated, since they are given by injection, and may not adequately control the disease. Those with breakthrough events require escalation to more potent agents, which are increasingly used off-label in pediatric MS despite limited data about safety or efficacy in children.”
To characterize the use and safety of newer DMTs in children with MS and clinically isolated syndrome (CIS), Dr. Krysko and colleagues conducted a retrospective cohort study of prospectively collected data at 12 clinics participating in the US Network of Pediatric MS Centers as of August 2017.
The researchers examined patterns of newer DMT use and newer DMT side effects. They classified DMTs as injectable (ie, glatiramer acetate and beta-interferons), oral (ie, dimethyl fumarate, fingolimod, and teriflunomide), or IV (ie, natalizumab, rituximab, alemtuzumab, and ocrelizumab). The researchers considered dimethyl fumarate, fingolimod, teriflunomide, natalizumab, rituximab, ocrelizumab, alemtuzumab, and daclizumab to be newer therapies.
The cohort included more than 1,000 patients with MS or CIS. In all, 618 patients had received a DMT before age 18 (587 patients with a diagnosis of MS at last follow-up and 31 patients with a diagnosis of CIS at last follow-up). About 66% were female, and patients’ mean age at MS onset was approximately 13.
The Use of Oral and IV DMTs
From 2008 to 2017, use of newer oral and IV DMTs increased overall and as first-line therapy in patients younger than 12 and in patients 12 or older. Of the 618 patients who received a DMT before age 18, 259 (42%) received a newer DMT, and 104 (17%) received a newer DMT as a first-line therapy.
Newer DMTs used in patients before age 18 included natalizumab in 101 patients, dimethyl fumarate in 100 patients, rituximab in 57 patients, fingolimod in 37 patients, daclizumab in five patients, and teriflunomide in three patients. Newer DMTs used as first-line therapy in patients before age 18 included dimethyl fumarate in 36 patients, natalizumab in 30 patients, rituximab in 22 patients, fingolimod in 14 patients, and teriflunomide in two patients.
Patients were exposed to dimethyl fumarate for 149 person-years, natalizumab for 140 person-years, rituximab for 75 person-years, fingolimod for 55 person-years, daclizumab for 10 person-years, and teriflunomide for one person-year.
Randomized controlled trials of the efficacy of DMTs in children with MS are ongoing. Future studies may explore predictors of newer DMT use in children with MS, the researchers said.
—Jake Remaly
SAN DIEGO—Newer oral and IV disease-modifying therapies (DMTs) for multiple sclerosis (MS) increasingly are used in children, according to data presented at the ACTRIMS 2018 Forum. These DMTs often are second-line therapies, but some patients receive them as first-line treatment.
“Newer DMTs … are being started more often over time at clinics participating in the US Network of Pediatric MS Centers,” said Kristen M. Krysko, MD, Clinical Fellow at the University of California, San Francisco School of Medicine, and colleagues.
The short-term side effect profile of newer DMTs in children is similar to that in adults. The study may have underestimated side effects, however, and long-term safety data are lacking, the researchers noted.
Treatment Challenges
About 5% of patients with MS develop symptoms before age 18. “Treatment of pediatric MS is challenging, given high relapse rates and the lack of safety and efficacy data for DMTs in children,” Dr. Krysko and colleagues said. “Conventionally, first-line treatments for pediatric MS include interferon beta and glatiramer acetate, but these agents may be poorly tolerated, since they are given by injection, and may not adequately control the disease. Those with breakthrough events require escalation to more potent agents, which are increasingly used off-label in pediatric MS despite limited data about safety or efficacy in children.”
To characterize the use and safety of newer DMTs in children with MS and clinically isolated syndrome (CIS), Dr. Krysko and colleagues conducted a retrospective cohort study of prospectively collected data at 12 clinics participating in the US Network of Pediatric MS Centers as of August 2017.
The researchers examined patterns of newer DMT use and newer DMT side effects. They classified DMTs as injectable (ie, glatiramer acetate and beta-interferons), oral (ie, dimethyl fumarate, fingolimod, and teriflunomide), or IV (ie, natalizumab, rituximab, alemtuzumab, and ocrelizumab). The researchers considered dimethyl fumarate, fingolimod, teriflunomide, natalizumab, rituximab, ocrelizumab, alemtuzumab, and daclizumab to be newer therapies.
The cohort included more than 1,000 patients with MS or CIS. In all, 618 patients had received a DMT before age 18 (587 patients with a diagnosis of MS at last follow-up and 31 patients with a diagnosis of CIS at last follow-up). About 66% were female, and patients’ mean age at MS onset was approximately 13.
The Use of Oral and IV DMTs
From 2008 to 2017, use of newer oral and IV DMTs increased overall and as first-line therapy in patients younger than 12 and in patients 12 or older. Of the 618 patients who received a DMT before age 18, 259 (42%) received a newer DMT, and 104 (17%) received a newer DMT as a first-line therapy.
Newer DMTs used in patients before age 18 included natalizumab in 101 patients, dimethyl fumarate in 100 patients, rituximab in 57 patients, fingolimod in 37 patients, daclizumab in five patients, and teriflunomide in three patients. Newer DMTs used as first-line therapy in patients before age 18 included dimethyl fumarate in 36 patients, natalizumab in 30 patients, rituximab in 22 patients, fingolimod in 14 patients, and teriflunomide in two patients.
Patients were exposed to dimethyl fumarate for 149 person-years, natalizumab for 140 person-years, rituximab for 75 person-years, fingolimod for 55 person-years, daclizumab for 10 person-years, and teriflunomide for one person-year.
Randomized controlled trials of the efficacy of DMTs in children with MS are ongoing. Future studies may explore predictors of newer DMT use in children with MS, the researchers said.
—Jake Remaly
Overweight and obese individuals face greater cardiovascular morbidity
.
In a report published online Feb. 28 in JAMA Cardiology, researchers presented an analysis of pooled data from 190,672 participants and 3.2 million person-years of follow-up in 10 prospective cohort studies, including the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Atherosclerosis Risk in Communities Study.
Incident cardiovascular events occurred in 37% of overweight middle-aged men and 28% of overweight middle-aged women. In obese middle-aged men and women, those figures were 47% and 39%, respectively, and in the morbidly obese they were 65% and 48%. By comparison, incident cardiovascular events occurred in 32% of middle-aged men of normal BMI, and 22% of women.
Across all the studies, there were 7,136 fatal or nonfatal myocardial infarctions, 3,733 fatal or nonfatal strokes, 4,614 diagnoses of heart failure, and 13,457 cardiovascular disease events during 856,532 person-years of follow-up in middle-aged adults.
After adjustment for age, ethnicity, and smoking status, the competing hazard ratios for experiencing a cardiovascular disease event compared to a noncardiovascular disease death were greater in the higher-BMI categories, and greatest among morbidly obese middle-aged men and women, largely because of a greater proportion of coronary heart disease and heart failure events.
“In addition, greater all-cause mortality in higher-BMI categories occurred at the expense of a greater proportion of deaths from cardiovascular causes in middle-aged men and women who are overweight and obese,” wrote Sadiya S. Khan, MD, MSc, of Northwestern University, Chicago, and her coauthors.
The research suggested that for each increasing unit of BMI in middle-aged men and women, the adjusted competing hazard ratios of incident cardiovascular disease events increased by a significant 5%.
The study found that middle-aged men in the normal and overweight BMI group enjoyed more years free from cardiovascular disease than did obese middle-aged men. In middle-aged women, those who were in the normal BMI range had significantly more years lived free of cardiovascular disease than did overweight or obese women.
The incidence of cardiovascular disease was significantly delayed by an average of 7.5 years in middle-aged men of normal BMI and 7.1 years in middle-aged women of normal BMI, compared with those with morbid obesity.
In terms of longevity, men and women with normal BMI lived on average 5.6 years and 2 years longer, respectively, than did men and women with morbid obesity.
“The results of this study build on prior research from the Cardiovascular Disease Lifetime Risk Pooling Project highlighting marked differences in lifetime risks of CVD and further highlight the importance of consideration of BMI as a risk factor for diminished healthy longevity and greater overall CVD morbidity and mortality,” the authors wrote.
The study was intended to address recent controversy over the health implications of overweight, with some evidence suggesting that overweight individuals have all-cause mortality similar to or lower than that of normal-weight groups.
“While we do observe evidence of the well-described overweight and obesity paradox, in which heavier individuals appear to live longer on average after diagnosis of CVD compared with individuals with normal BMI, our data when following up individuals prior to the onset of CVD indicate that this occurs because of a trend toward earlier onset of disease in individuals who are overweight and obese,” they wrote.
The study did not account for change in BMI over the course of follow-up, nor did it use data on fat distribution or the degree of visceral adiposity, the researchers noted.
“Additional important outcomes of obesity-related morbidity, such as atrial fibrillation, sleep-disordered breathing, and chronic liver disease, were not ascertained routinely in our cohort studies, and we likely underestimated the overall comorbidity burden of excess weight.”
The National Heart, Lung, and Blood Institute supported the study. No conflicts of interest were declared.
SOURCE: Khan SS et al. JAMA Cardiol. 2018 Feb 28. doi: 10.1001/jamacardio.2018.0022.
.
In a report published online Feb. 28 in JAMA Cardiology, researchers presented an analysis of pooled data from 190,672 participants and 3.2 million person-years of follow-up in 10 prospective cohort studies, including the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Atherosclerosis Risk in Communities Study.
Incident cardiovascular events occurred in 37% of overweight middle-aged men and 28% of overweight middle-aged women. In obese middle-aged men and women, those figures were 47% and 39%, respectively, and in the morbidly obese they were 65% and 48%. By comparison, incident cardiovascular events occurred in 32% of middle-aged men of normal BMI, and 22% of women.
Across all the studies, there were 7,136 fatal or nonfatal myocardial infarctions, 3,733 fatal or nonfatal strokes, 4,614 diagnoses of heart failure, and 13,457 cardiovascular disease events during 856,532 person-years of follow-up in middle-aged adults.
After adjustment for age, ethnicity, and smoking status, the competing hazard ratios for experiencing a cardiovascular disease event compared to a noncardiovascular disease death were greater in the higher-BMI categories, and greatest among morbidly obese middle-aged men and women, largely because of a greater proportion of coronary heart disease and heart failure events.
“In addition, greater all-cause mortality in higher-BMI categories occurred at the expense of a greater proportion of deaths from cardiovascular causes in middle-aged men and women who are overweight and obese,” wrote Sadiya S. Khan, MD, MSc, of Northwestern University, Chicago, and her coauthors.
The research suggested that for each increasing unit of BMI in middle-aged men and women, the adjusted competing hazard ratios of incident cardiovascular disease events increased by a significant 5%.
The study found that middle-aged men in the normal and overweight BMI group enjoyed more years free from cardiovascular disease than did obese middle-aged men. In middle-aged women, those who were in the normal BMI range had significantly more years lived free of cardiovascular disease than did overweight or obese women.
The incidence of cardiovascular disease was significantly delayed by an average of 7.5 years in middle-aged men of normal BMI and 7.1 years in middle-aged women of normal BMI, compared with those with morbid obesity.
In terms of longevity, men and women with normal BMI lived on average 5.6 years and 2 years longer, respectively, than did men and women with morbid obesity.
“The results of this study build on prior research from the Cardiovascular Disease Lifetime Risk Pooling Project highlighting marked differences in lifetime risks of CVD and further highlight the importance of consideration of BMI as a risk factor for diminished healthy longevity and greater overall CVD morbidity and mortality,” the authors wrote.
The study was intended to address recent controversy over the health implications of overweight, with some evidence suggesting that overweight individuals have all-cause mortality similar to or lower than that of normal-weight groups.
“While we do observe evidence of the well-described overweight and obesity paradox, in which heavier individuals appear to live longer on average after diagnosis of CVD compared with individuals with normal BMI, our data when following up individuals prior to the onset of CVD indicate that this occurs because of a trend toward earlier onset of disease in individuals who are overweight and obese,” they wrote.
The study did not account for change in BMI over the course of follow-up, nor did it use data on fat distribution or the degree of visceral adiposity, the researchers noted.
“Additional important outcomes of obesity-related morbidity, such as atrial fibrillation, sleep-disordered breathing, and chronic liver disease, were not ascertained routinely in our cohort studies, and we likely underestimated the overall comorbidity burden of excess weight.”
The National Heart, Lung, and Blood Institute supported the study. No conflicts of interest were declared.
SOURCE: Khan SS et al. JAMA Cardiol. 2018 Feb 28. doi: 10.1001/jamacardio.2018.0022.
.
In a report published online Feb. 28 in JAMA Cardiology, researchers presented an analysis of pooled data from 190,672 participants and 3.2 million person-years of follow-up in 10 prospective cohort studies, including the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Atherosclerosis Risk in Communities Study.
Incident cardiovascular events occurred in 37% of overweight middle-aged men and 28% of overweight middle-aged women. In obese middle-aged men and women, those figures were 47% and 39%, respectively, and in the morbidly obese they were 65% and 48%. By comparison, incident cardiovascular events occurred in 32% of middle-aged men of normal BMI, and 22% of women.
Across all the studies, there were 7,136 fatal or nonfatal myocardial infarctions, 3,733 fatal or nonfatal strokes, 4,614 diagnoses of heart failure, and 13,457 cardiovascular disease events during 856,532 person-years of follow-up in middle-aged adults.
After adjustment for age, ethnicity, and smoking status, the competing hazard ratios for experiencing a cardiovascular disease event compared to a noncardiovascular disease death were greater in the higher-BMI categories, and greatest among morbidly obese middle-aged men and women, largely because of a greater proportion of coronary heart disease and heart failure events.
“In addition, greater all-cause mortality in higher-BMI categories occurred at the expense of a greater proportion of deaths from cardiovascular causes in middle-aged men and women who are overweight and obese,” wrote Sadiya S. Khan, MD, MSc, of Northwestern University, Chicago, and her coauthors.
The research suggested that for each increasing unit of BMI in middle-aged men and women, the adjusted competing hazard ratios of incident cardiovascular disease events increased by a significant 5%.
The study found that middle-aged men in the normal and overweight BMI group enjoyed more years free from cardiovascular disease than did obese middle-aged men. In middle-aged women, those who were in the normal BMI range had significantly more years lived free of cardiovascular disease than did overweight or obese women.
The incidence of cardiovascular disease was significantly delayed by an average of 7.5 years in middle-aged men of normal BMI and 7.1 years in middle-aged women of normal BMI, compared with those with morbid obesity.
In terms of longevity, men and women with normal BMI lived on average 5.6 years and 2 years longer, respectively, than did men and women with morbid obesity.
“The results of this study build on prior research from the Cardiovascular Disease Lifetime Risk Pooling Project highlighting marked differences in lifetime risks of CVD and further highlight the importance of consideration of BMI as a risk factor for diminished healthy longevity and greater overall CVD morbidity and mortality,” the authors wrote.
The study was intended to address recent controversy over the health implications of overweight, with some evidence suggesting that overweight individuals have all-cause mortality similar to or lower than that of normal-weight groups.
“While we do observe evidence of the well-described overweight and obesity paradox, in which heavier individuals appear to live longer on average after diagnosis of CVD compared with individuals with normal BMI, our data when following up individuals prior to the onset of CVD indicate that this occurs because of a trend toward earlier onset of disease in individuals who are overweight and obese,” they wrote.
The study did not account for change in BMI over the course of follow-up, nor did it use data on fat distribution or the degree of visceral adiposity, the researchers noted.
“Additional important outcomes of obesity-related morbidity, such as atrial fibrillation, sleep-disordered breathing, and chronic liver disease, were not ascertained routinely in our cohort studies, and we likely underestimated the overall comorbidity burden of excess weight.”
The National Heart, Lung, and Blood Institute supported the study. No conflicts of interest were declared.
SOURCE: Khan SS et al. JAMA Cardiol. 2018 Feb 28. doi: 10.1001/jamacardio.2018.0022.
FROM JAMA CARDIOLOGY
Key clinical point: Obese individuals have shorter life spans and spend significantly more time dealing with the burden of cardiovascular morbidity than do normal-weight individuals.
Major finding: Overweight and obese middle-aged individuals have a significantly higher incidence of cardiovascular events and mortality compared with normal-weight middle-aged individuals.
Data source: Analysis of pooled data from 190,672 participants and 3.2 million person-years of follow-up in 10 prospective cohort studies.
Disclosures: The National Heart, Lung, and Blood Institute supported the study. No conflicts of interest were declared.
Source: Khan SS et al. JAMA Cardiol. 2018 Feb 28. doi: 10.1001/jamacardio.2018.0022