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Myasthenia gravis drug gets FDA nod
, the drug’s manufacturer, UCB, has announced.
Rozanolixizumab is a subcutaneous-infused humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn), reducing the concentration of pathogenic IgG autoantibodies.
U.S. approval is based on results of the phase 3 MycarinG study involving 200 patients with AChR or MuSK autoantibody-positive gMG. Patients were randomly assigned to one of two rozanolixizumab groups (7 mg/kg or 10 mg/kg) or placebo for 6 weeks.
As reported last month in Lancet Neurology, rozanolixizumab led to statistically significant improvements in gMG-specific outcomes, including everyday activities such as breathing, talking, swallowing, and being able to rise from a chair.
“There is a significant need for new, innovative treatment options to reduce the day-to-day burden of gMG,” lead investigator Vera Bril, MD, professor of medicine (neurology), University of Toronto, said in a news release.
Rozanolixizumab is “a new treatment option, targeting one of the mechanisms of disease to provide symptom improvement in patient- and physician-reported outcomes at day 43,” Dr. Bril added.
The most common adverse reactions (reported in at least 10% of patients treated with rozanolixizumab) were headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea.
The company expects rozanolixizumab to be available in the United States during the third quarter of 2023.
The FDA granted the application for rozanolixizumab in gMG priority review.
A version of this article first appeared on Medscape.com.
, the drug’s manufacturer, UCB, has announced.
Rozanolixizumab is a subcutaneous-infused humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn), reducing the concentration of pathogenic IgG autoantibodies.
U.S. approval is based on results of the phase 3 MycarinG study involving 200 patients with AChR or MuSK autoantibody-positive gMG. Patients were randomly assigned to one of two rozanolixizumab groups (7 mg/kg or 10 mg/kg) or placebo for 6 weeks.
As reported last month in Lancet Neurology, rozanolixizumab led to statistically significant improvements in gMG-specific outcomes, including everyday activities such as breathing, talking, swallowing, and being able to rise from a chair.
“There is a significant need for new, innovative treatment options to reduce the day-to-day burden of gMG,” lead investigator Vera Bril, MD, professor of medicine (neurology), University of Toronto, said in a news release.
Rozanolixizumab is “a new treatment option, targeting one of the mechanisms of disease to provide symptom improvement in patient- and physician-reported outcomes at day 43,” Dr. Bril added.
The most common adverse reactions (reported in at least 10% of patients treated with rozanolixizumab) were headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea.
The company expects rozanolixizumab to be available in the United States during the third quarter of 2023.
The FDA granted the application for rozanolixizumab in gMG priority review.
A version of this article first appeared on Medscape.com.
, the drug’s manufacturer, UCB, has announced.
Rozanolixizumab is a subcutaneous-infused humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn), reducing the concentration of pathogenic IgG autoantibodies.
U.S. approval is based on results of the phase 3 MycarinG study involving 200 patients with AChR or MuSK autoantibody-positive gMG. Patients were randomly assigned to one of two rozanolixizumab groups (7 mg/kg or 10 mg/kg) or placebo for 6 weeks.
As reported last month in Lancet Neurology, rozanolixizumab led to statistically significant improvements in gMG-specific outcomes, including everyday activities such as breathing, talking, swallowing, and being able to rise from a chair.
“There is a significant need for new, innovative treatment options to reduce the day-to-day burden of gMG,” lead investigator Vera Bril, MD, professor of medicine (neurology), University of Toronto, said in a news release.
Rozanolixizumab is “a new treatment option, targeting one of the mechanisms of disease to provide symptom improvement in patient- and physician-reported outcomes at day 43,” Dr. Bril added.
The most common adverse reactions (reported in at least 10% of patients treated with rozanolixizumab) were headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea.
The company expects rozanolixizumab to be available in the United States during the third quarter of 2023.
The FDA granted the application for rozanolixizumab in gMG priority review.
A version of this article first appeared on Medscape.com.
U.S. incidence, prevalence of myasthenia gravis is rising
, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be due to “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.
Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.
Myasthenia gravis is a rare neuromuscular disease characterized by muscle weakness and fatigue caused by the binding of autoantibodies at the neuromuscular junction. It affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.
In Europe, the incidence and prevalence of myasthenia gravis has increased for the past several decades. In the United States, increasing prevalence has also been observed, but recent estimates are lacking, making it tough to gauge the true burden of disease, Dr. Rodrigues explained.
Claims-based analysis
To investigate, Dr. Rodrigues and colleagues analyzed claims data (commercial, Medicare, and Medicaid) and electronic health records representing over 300 million patients in the United States from 2011 to present.
They calculated sex- and age-specific incidence and prevalence of myasthenia gravis for the year 2021 using U.S. Census data.
Prevalent patients were identified as having one or more myasthenia gravis records in 2021 and two or more myasthenia gravis records, at least 30 days apart, from 2016 to 2021. This cohort had 78,225 patients.
Incident patients were identified as those with a myasthenia gravis record in 2021 and no previous myasthenia gravis record from 2019 to 2020. This cohort had 4,214 patients.
For both the prevalent and incident cohort, the distribution of male and female patients was roughly 50/50, with a slightly higher proportion of females in the incident cohort, Dr. Rodrigues reported.
When looking at age groups, there were “very few pediatric patients,” she noted, with less than 1% of the patients under the age of 12. The highest proportion of patients were 65 years or older. The mean age was 67 in the prevalent cohort and 68 in the incident cohort.
In 2021, the overall incidence of myasthenia gravis was 3.2 per 100,000 with similar estimates for males and females (3.2 vs. 3.1 per 100,000, respectively).
Total prevalence was estimated to be 37.0 per 100,000 with sex-specific estimates being comparable at 37.3 and 36.7 per 100,000 for males and females, respectively.
The incidence and prevalence of myasthenia gravis increased with age, ranging from 0.3 and 0.4 per 100,000, respectively, in children younger than age 2 years, to 10.2 and 116.8 per 100,000, respectively, in people 65 and older.
These estimates are “significantly higher” than those from a prior U.S. analysis from 2003, Dr. Rodrigues told attendees, but they are quite similar to the estimates that were reported in Sweden in 2020.
A limitation of the analysis is that patients who do not seek care regularly may have not been identified due to inclusion criteria, potentially leading to underestimates. Also, no information was available on the myasthenia gravis subtype (ocular vs. generalized).
Underestimated burden
Reached for comment, Richard J. Nowak, MD, MS, director of the Yale Myasthenia Gravis Clinic, Yale School of Medicine, New Haven, Conn., noted that the new report, “albeit limited as a claims-based analysis, presents modern data on incidence and prevalence of myasthenia gravis in the United States.”
“It suggests that the current estimates of myasthenia gravis in the United States are too low and that the true impact/burden of myasthenia gravis is greater. While we are unable to verify the accuracy of the diagnosis, the total myasthenia gravis population is likely to be about 100,000, which is higher than prior estimates.”
“This, in fact, might be driven by greater disease awareness and increased diagnosis along with decreased mortality and longer life expectancy,” Dr. Nowak said.
“Anecdotally, we are most certainly seeing patients with new-onset myasthenia gravis in their 70s, 80s, and even 90s in recent years. The EXPLORE-MG registry published data from a tertiary center on age of onset breakdown showing myasthenia gravis can present at any age,” Dr. Nowak added.
Funding for the study was provided by Alexion, AstraZeneca Rare Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases. Dr. Nowak has no relevant disclosures.
A version of this article originally appeared on Medscape.com.
, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be due to “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.
Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.
Myasthenia gravis is a rare neuromuscular disease characterized by muscle weakness and fatigue caused by the binding of autoantibodies at the neuromuscular junction. It affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.
In Europe, the incidence and prevalence of myasthenia gravis has increased for the past several decades. In the United States, increasing prevalence has also been observed, but recent estimates are lacking, making it tough to gauge the true burden of disease, Dr. Rodrigues explained.
Claims-based analysis
To investigate, Dr. Rodrigues and colleagues analyzed claims data (commercial, Medicare, and Medicaid) and electronic health records representing over 300 million patients in the United States from 2011 to present.
They calculated sex- and age-specific incidence and prevalence of myasthenia gravis for the year 2021 using U.S. Census data.
Prevalent patients were identified as having one or more myasthenia gravis records in 2021 and two or more myasthenia gravis records, at least 30 days apart, from 2016 to 2021. This cohort had 78,225 patients.
Incident patients were identified as those with a myasthenia gravis record in 2021 and no previous myasthenia gravis record from 2019 to 2020. This cohort had 4,214 patients.
For both the prevalent and incident cohort, the distribution of male and female patients was roughly 50/50, with a slightly higher proportion of females in the incident cohort, Dr. Rodrigues reported.
When looking at age groups, there were “very few pediatric patients,” she noted, with less than 1% of the patients under the age of 12. The highest proportion of patients were 65 years or older. The mean age was 67 in the prevalent cohort and 68 in the incident cohort.
In 2021, the overall incidence of myasthenia gravis was 3.2 per 100,000 with similar estimates for males and females (3.2 vs. 3.1 per 100,000, respectively).
Total prevalence was estimated to be 37.0 per 100,000 with sex-specific estimates being comparable at 37.3 and 36.7 per 100,000 for males and females, respectively.
The incidence and prevalence of myasthenia gravis increased with age, ranging from 0.3 and 0.4 per 100,000, respectively, in children younger than age 2 years, to 10.2 and 116.8 per 100,000, respectively, in people 65 and older.
These estimates are “significantly higher” than those from a prior U.S. analysis from 2003, Dr. Rodrigues told attendees, but they are quite similar to the estimates that were reported in Sweden in 2020.
A limitation of the analysis is that patients who do not seek care regularly may have not been identified due to inclusion criteria, potentially leading to underestimates. Also, no information was available on the myasthenia gravis subtype (ocular vs. generalized).
Underestimated burden
Reached for comment, Richard J. Nowak, MD, MS, director of the Yale Myasthenia Gravis Clinic, Yale School of Medicine, New Haven, Conn., noted that the new report, “albeit limited as a claims-based analysis, presents modern data on incidence and prevalence of myasthenia gravis in the United States.”
“It suggests that the current estimates of myasthenia gravis in the United States are too low and that the true impact/burden of myasthenia gravis is greater. While we are unable to verify the accuracy of the diagnosis, the total myasthenia gravis population is likely to be about 100,000, which is higher than prior estimates.”
“This, in fact, might be driven by greater disease awareness and increased diagnosis along with decreased mortality and longer life expectancy,” Dr. Nowak said.
“Anecdotally, we are most certainly seeing patients with new-onset myasthenia gravis in their 70s, 80s, and even 90s in recent years. The EXPLORE-MG registry published data from a tertiary center on age of onset breakdown showing myasthenia gravis can present at any age,” Dr. Nowak added.
Funding for the study was provided by Alexion, AstraZeneca Rare Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases. Dr. Nowak has no relevant disclosures.
A version of this article originally appeared on Medscape.com.
, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be due to “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.
Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.
Myasthenia gravis is a rare neuromuscular disease characterized by muscle weakness and fatigue caused by the binding of autoantibodies at the neuromuscular junction. It affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.
In Europe, the incidence and prevalence of myasthenia gravis has increased for the past several decades. In the United States, increasing prevalence has also been observed, but recent estimates are lacking, making it tough to gauge the true burden of disease, Dr. Rodrigues explained.
Claims-based analysis
To investigate, Dr. Rodrigues and colleagues analyzed claims data (commercial, Medicare, and Medicaid) and electronic health records representing over 300 million patients in the United States from 2011 to present.
They calculated sex- and age-specific incidence and prevalence of myasthenia gravis for the year 2021 using U.S. Census data.
Prevalent patients were identified as having one or more myasthenia gravis records in 2021 and two or more myasthenia gravis records, at least 30 days apart, from 2016 to 2021. This cohort had 78,225 patients.
Incident patients were identified as those with a myasthenia gravis record in 2021 and no previous myasthenia gravis record from 2019 to 2020. This cohort had 4,214 patients.
For both the prevalent and incident cohort, the distribution of male and female patients was roughly 50/50, with a slightly higher proportion of females in the incident cohort, Dr. Rodrigues reported.
When looking at age groups, there were “very few pediatric patients,” she noted, with less than 1% of the patients under the age of 12. The highest proportion of patients were 65 years or older. The mean age was 67 in the prevalent cohort and 68 in the incident cohort.
In 2021, the overall incidence of myasthenia gravis was 3.2 per 100,000 with similar estimates for males and females (3.2 vs. 3.1 per 100,000, respectively).
Total prevalence was estimated to be 37.0 per 100,000 with sex-specific estimates being comparable at 37.3 and 36.7 per 100,000 for males and females, respectively.
The incidence and prevalence of myasthenia gravis increased with age, ranging from 0.3 and 0.4 per 100,000, respectively, in children younger than age 2 years, to 10.2 and 116.8 per 100,000, respectively, in people 65 and older.
These estimates are “significantly higher” than those from a prior U.S. analysis from 2003, Dr. Rodrigues told attendees, but they are quite similar to the estimates that were reported in Sweden in 2020.
A limitation of the analysis is that patients who do not seek care regularly may have not been identified due to inclusion criteria, potentially leading to underestimates. Also, no information was available on the myasthenia gravis subtype (ocular vs. generalized).
Underestimated burden
Reached for comment, Richard J. Nowak, MD, MS, director of the Yale Myasthenia Gravis Clinic, Yale School of Medicine, New Haven, Conn., noted that the new report, “albeit limited as a claims-based analysis, presents modern data on incidence and prevalence of myasthenia gravis in the United States.”
“It suggests that the current estimates of myasthenia gravis in the United States are too low and that the true impact/burden of myasthenia gravis is greater. While we are unable to verify the accuracy of the diagnosis, the total myasthenia gravis population is likely to be about 100,000, which is higher than prior estimates.”
“This, in fact, might be driven by greater disease awareness and increased diagnosis along with decreased mortality and longer life expectancy,” Dr. Nowak said.
“Anecdotally, we are most certainly seeing patients with new-onset myasthenia gravis in their 70s, 80s, and even 90s in recent years. The EXPLORE-MG registry published data from a tertiary center on age of onset breakdown showing myasthenia gravis can present at any age,” Dr. Nowak added.
Funding for the study was provided by Alexion, AstraZeneca Rare Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases. Dr. Nowak has no relevant disclosures.
A version of this article originally appeared on Medscape.com.
From AAN 2023
Therapy to reverse muscle dystrophies shows promise
BOSTON – Becker (BMD) and Duchenne muscle dystrophy (DMD) progress largely from irreversible contraction-induced injury of skeletal muscles, making the very positive interim results of an early-phase trial with a drug that prevents these injuries worth attention.
The phase 1b data in BMD, presented at the 2023 annual meeting of the American Academy of Neurology, were sufficiently promising that controlled phase 2 trials in both BMD and DMD are already enrolling, reported Joanne Donovan, MD, PhD, an adjunct professor at Boston University and chief medical officer of Edgewise Therapeutics, the company developing the drug.
Phase 1 study
Early phase studies are largely focused on safety, but the
Moreover, the evidence of a clinical effect was achieved in adult patients with a North Star Ambulatory Assessment (NSAA) score of 15, signifying advanced disease. Only 12 patients were enrolled and there were no controls, but objective evidence of a favorable effect was generated by highly significant reductions in creatine kinase (CK) and fast skeletal muscle (TNNI2) troponin, which are both biomarkers commonly used to track muscular dystrophy progression.
In patients with BMD or DMD, a lack of dystrophin is a key pathogenic feature, according to Dr. Donovan. She explained that dystrophin in muscles connects contractile proteins to membranes and surrounding matrix. In the presence of dystrophin, muscle fibers support each other, but when this protein is absent, contraction causes injury.
The drug in development, currently identified as EDG-5506, is a selective fast myosin inhibitor. This agent was shown to prevent the muscle injury caused by lack of dystrophin in animal models of muscular dystrophy and is now showing the same effect in humans. Preservation of muscle is critical to preventing BMD and DMD progression according to several sets of data, according to Dr. Donovan.
For one, it has been shown that BMD or DMD patients with relatively preserved function as defined by a NSAA score above 32 have minimal muscle damage. As NSAA scores fall below 32 points, muscle mass diminishes and fat accumulates. In natural history studies of BMD, there is a 1.2-point decline in NSAA score over 5 years, and this tracks with muscle loss and not with other variables, such as patient age.
“Progression depends on the degree of muscle loss,” Dr. Donovan stated, providing the rationale for moving forward with EDG-5506.
Proof of concept
In experimental studies, modulation of fast myelin provided complete protection against muscle injury while preserving its contractile function, and this translated into protection against loss of function. Phase 1 studies in BMD patients and healthy controls have already provided evidence that EDG-5506 is well tolerated and safe, but the new phase 1b provides a proof of concept for its ability to inhibit muscle injury in BMD patients.
In this study, called ARCH, 12 adults 18 years of age or older with a dystrophin mutation and a BMD phenotype who could complete a 100-meter timed test were enrolled. The median age at entry was 32 years. Several patients had participated in a previous phase 1 safety study. The daily starting dose of 10 mg was increased from 10 mg to 15 mg at 2 months. The dose was increased again to 20 mg at 6 months, but the data presented by Dr. Donovan were restricted to the first 6 months.
At the interim 6-month analysis, creatine kinase was reduced by 40% and TINN2 was reduced by 84% (both P < 0.001). The significant reductions in these biomarkers and others, such as myoglobin, were mostly achieved within the first month, although further reductions were observed for some biomarkers subsequently.
The NSAA score at 6 months improved on average by about 1 point on treatment. Natural history studies of BMD predict a 1-point reduction in NSAA score over this period of time. The modest improvements from baseline in pain scores at 1 month were sustained at 6 months.
On the basis of a proteomic analysis, 125 proteins mostly associated with metabolic pathways consistent with muscle injury were found to be altered in BMD patients relative to healthy controls. The majority of these proteins, whether assessed collectively or individually, normalized after 1 to 2 months of treatment with EDG-5506 and have remained stable during follow-up to date, according to Dr. Donovan.
As in previous studies, the drug was well tolerated. The three most common treatment-emergent events were dizziness, somnolence, and headache. Each was reported by about 25% of patients, but no patient discontinued therapy as a result of adverse events.
Findings deemed ‘a big deal’
These data, despite the small number of patients in the study and the limited follow-up, “are a big deal,” according to Nicholas E. Johnson, MD, division chief, neuromuscular disorders, Virginia Commonwealth University, Richmond. He pointed out that there are no effective treatments currently for BMD, and the mechanism of action is plausible.
“I am excited about the potential of this treatment, although we clearly need longer follow-up and more patients evaluated on this treatment,” Dr. Johnson said. He said that clinicians with BMD patients should be aware of the phase 2 trial that is now recruiting adult subjects.
“Becker muscular dystrophy is highly disabling. As disease advances, most patients have very limited function,” said Dr. Johnson, emphasizing the urgent unmet need for an effective therapy.
Dr. Donovan is a full time employee of Edgewise Therapeutics, which funded this study. Dr. Johnson has financial relationships with Acceleron, Arthex, AveXis, Avidity, Biogen, Dyne Therapeutics, Entrada, Juvena, ML Bio, Sarepta Therapeutics, Triplet Therapeutics, and Vertex Pharma.
BOSTON – Becker (BMD) and Duchenne muscle dystrophy (DMD) progress largely from irreversible contraction-induced injury of skeletal muscles, making the very positive interim results of an early-phase trial with a drug that prevents these injuries worth attention.
The phase 1b data in BMD, presented at the 2023 annual meeting of the American Academy of Neurology, were sufficiently promising that controlled phase 2 trials in both BMD and DMD are already enrolling, reported Joanne Donovan, MD, PhD, an adjunct professor at Boston University and chief medical officer of Edgewise Therapeutics, the company developing the drug.
Phase 1 study
Early phase studies are largely focused on safety, but the
Moreover, the evidence of a clinical effect was achieved in adult patients with a North Star Ambulatory Assessment (NSAA) score of 15, signifying advanced disease. Only 12 patients were enrolled and there were no controls, but objective evidence of a favorable effect was generated by highly significant reductions in creatine kinase (CK) and fast skeletal muscle (TNNI2) troponin, which are both biomarkers commonly used to track muscular dystrophy progression.
In patients with BMD or DMD, a lack of dystrophin is a key pathogenic feature, according to Dr. Donovan. She explained that dystrophin in muscles connects contractile proteins to membranes and surrounding matrix. In the presence of dystrophin, muscle fibers support each other, but when this protein is absent, contraction causes injury.
The drug in development, currently identified as EDG-5506, is a selective fast myosin inhibitor. This agent was shown to prevent the muscle injury caused by lack of dystrophin in animal models of muscular dystrophy and is now showing the same effect in humans. Preservation of muscle is critical to preventing BMD and DMD progression according to several sets of data, according to Dr. Donovan.
For one, it has been shown that BMD or DMD patients with relatively preserved function as defined by a NSAA score above 32 have minimal muscle damage. As NSAA scores fall below 32 points, muscle mass diminishes and fat accumulates. In natural history studies of BMD, there is a 1.2-point decline in NSAA score over 5 years, and this tracks with muscle loss and not with other variables, such as patient age.
“Progression depends on the degree of muscle loss,” Dr. Donovan stated, providing the rationale for moving forward with EDG-5506.
Proof of concept
In experimental studies, modulation of fast myelin provided complete protection against muscle injury while preserving its contractile function, and this translated into protection against loss of function. Phase 1 studies in BMD patients and healthy controls have already provided evidence that EDG-5506 is well tolerated and safe, but the new phase 1b provides a proof of concept for its ability to inhibit muscle injury in BMD patients.
In this study, called ARCH, 12 adults 18 years of age or older with a dystrophin mutation and a BMD phenotype who could complete a 100-meter timed test were enrolled. The median age at entry was 32 years. Several patients had participated in a previous phase 1 safety study. The daily starting dose of 10 mg was increased from 10 mg to 15 mg at 2 months. The dose was increased again to 20 mg at 6 months, but the data presented by Dr. Donovan were restricted to the first 6 months.
At the interim 6-month analysis, creatine kinase was reduced by 40% and TINN2 was reduced by 84% (both P < 0.001). The significant reductions in these biomarkers and others, such as myoglobin, were mostly achieved within the first month, although further reductions were observed for some biomarkers subsequently.
The NSAA score at 6 months improved on average by about 1 point on treatment. Natural history studies of BMD predict a 1-point reduction in NSAA score over this period of time. The modest improvements from baseline in pain scores at 1 month were sustained at 6 months.
On the basis of a proteomic analysis, 125 proteins mostly associated with metabolic pathways consistent with muscle injury were found to be altered in BMD patients relative to healthy controls. The majority of these proteins, whether assessed collectively or individually, normalized after 1 to 2 months of treatment with EDG-5506 and have remained stable during follow-up to date, according to Dr. Donovan.
As in previous studies, the drug was well tolerated. The three most common treatment-emergent events were dizziness, somnolence, and headache. Each was reported by about 25% of patients, but no patient discontinued therapy as a result of adverse events.
Findings deemed ‘a big deal’
These data, despite the small number of patients in the study and the limited follow-up, “are a big deal,” according to Nicholas E. Johnson, MD, division chief, neuromuscular disorders, Virginia Commonwealth University, Richmond. He pointed out that there are no effective treatments currently for BMD, and the mechanism of action is plausible.
“I am excited about the potential of this treatment, although we clearly need longer follow-up and more patients evaluated on this treatment,” Dr. Johnson said. He said that clinicians with BMD patients should be aware of the phase 2 trial that is now recruiting adult subjects.
“Becker muscular dystrophy is highly disabling. As disease advances, most patients have very limited function,” said Dr. Johnson, emphasizing the urgent unmet need for an effective therapy.
Dr. Donovan is a full time employee of Edgewise Therapeutics, which funded this study. Dr. Johnson has financial relationships with Acceleron, Arthex, AveXis, Avidity, Biogen, Dyne Therapeutics, Entrada, Juvena, ML Bio, Sarepta Therapeutics, Triplet Therapeutics, and Vertex Pharma.
BOSTON – Becker (BMD) and Duchenne muscle dystrophy (DMD) progress largely from irreversible contraction-induced injury of skeletal muscles, making the very positive interim results of an early-phase trial with a drug that prevents these injuries worth attention.
The phase 1b data in BMD, presented at the 2023 annual meeting of the American Academy of Neurology, were sufficiently promising that controlled phase 2 trials in both BMD and DMD are already enrolling, reported Joanne Donovan, MD, PhD, an adjunct professor at Boston University and chief medical officer of Edgewise Therapeutics, the company developing the drug.
Phase 1 study
Early phase studies are largely focused on safety, but the
Moreover, the evidence of a clinical effect was achieved in adult patients with a North Star Ambulatory Assessment (NSAA) score of 15, signifying advanced disease. Only 12 patients were enrolled and there were no controls, but objective evidence of a favorable effect was generated by highly significant reductions in creatine kinase (CK) and fast skeletal muscle (TNNI2) troponin, which are both biomarkers commonly used to track muscular dystrophy progression.
In patients with BMD or DMD, a lack of dystrophin is a key pathogenic feature, according to Dr. Donovan. She explained that dystrophin in muscles connects contractile proteins to membranes and surrounding matrix. In the presence of dystrophin, muscle fibers support each other, but when this protein is absent, contraction causes injury.
The drug in development, currently identified as EDG-5506, is a selective fast myosin inhibitor. This agent was shown to prevent the muscle injury caused by lack of dystrophin in animal models of muscular dystrophy and is now showing the same effect in humans. Preservation of muscle is critical to preventing BMD and DMD progression according to several sets of data, according to Dr. Donovan.
For one, it has been shown that BMD or DMD patients with relatively preserved function as defined by a NSAA score above 32 have minimal muscle damage. As NSAA scores fall below 32 points, muscle mass diminishes and fat accumulates. In natural history studies of BMD, there is a 1.2-point decline in NSAA score over 5 years, and this tracks with muscle loss and not with other variables, such as patient age.
“Progression depends on the degree of muscle loss,” Dr. Donovan stated, providing the rationale for moving forward with EDG-5506.
Proof of concept
In experimental studies, modulation of fast myelin provided complete protection against muscle injury while preserving its contractile function, and this translated into protection against loss of function. Phase 1 studies in BMD patients and healthy controls have already provided evidence that EDG-5506 is well tolerated and safe, but the new phase 1b provides a proof of concept for its ability to inhibit muscle injury in BMD patients.
In this study, called ARCH, 12 adults 18 years of age or older with a dystrophin mutation and a BMD phenotype who could complete a 100-meter timed test were enrolled. The median age at entry was 32 years. Several patients had participated in a previous phase 1 safety study. The daily starting dose of 10 mg was increased from 10 mg to 15 mg at 2 months. The dose was increased again to 20 mg at 6 months, but the data presented by Dr. Donovan were restricted to the first 6 months.
At the interim 6-month analysis, creatine kinase was reduced by 40% and TINN2 was reduced by 84% (both P < 0.001). The significant reductions in these biomarkers and others, such as myoglobin, were mostly achieved within the first month, although further reductions were observed for some biomarkers subsequently.
The NSAA score at 6 months improved on average by about 1 point on treatment. Natural history studies of BMD predict a 1-point reduction in NSAA score over this period of time. The modest improvements from baseline in pain scores at 1 month were sustained at 6 months.
On the basis of a proteomic analysis, 125 proteins mostly associated with metabolic pathways consistent with muscle injury were found to be altered in BMD patients relative to healthy controls. The majority of these proteins, whether assessed collectively or individually, normalized after 1 to 2 months of treatment with EDG-5506 and have remained stable during follow-up to date, according to Dr. Donovan.
As in previous studies, the drug was well tolerated. The three most common treatment-emergent events were dizziness, somnolence, and headache. Each was reported by about 25% of patients, but no patient discontinued therapy as a result of adverse events.
Findings deemed ‘a big deal’
These data, despite the small number of patients in the study and the limited follow-up, “are a big deal,” according to Nicholas E. Johnson, MD, division chief, neuromuscular disorders, Virginia Commonwealth University, Richmond. He pointed out that there are no effective treatments currently for BMD, and the mechanism of action is plausible.
“I am excited about the potential of this treatment, although we clearly need longer follow-up and more patients evaluated on this treatment,” Dr. Johnson said. He said that clinicians with BMD patients should be aware of the phase 2 trial that is now recruiting adult subjects.
“Becker muscular dystrophy is highly disabling. As disease advances, most patients have very limited function,” said Dr. Johnson, emphasizing the urgent unmet need for an effective therapy.
Dr. Donovan is a full time employee of Edgewise Therapeutics, which funded this study. Dr. Johnson has financial relationships with Acceleron, Arthex, AveXis, Avidity, Biogen, Dyne Therapeutics, Entrada, Juvena, ML Bio, Sarepta Therapeutics, Triplet Therapeutics, and Vertex Pharma.
FROM AAN 2023
Childhood trauma tied to increased Parkinson’s disease severity
new research shows.
Results of the first study to evaluate the relationship between childhood trauma and PD investigators found that the relationship appears to be dose dependent. Patients with PD who reported more than one ACE all experienced a statistically significant decrease in QOL, and for each additional ACE, there was significant worsening of motor symptoms.
This study supports a recent-call to-action paper in JAMA Neurology encouraging adoption of “trauma-informed neurology,” study investigator Indu Subramanian, MD, clinical professor, department of neurology, University of California, Los Angeles, said in an interview.
“We need to start asking about ACEs in everyone. It should be part of our medical intake,” said Dr. Subramanian, who is also the director of the Southwest Parkinson’s Disease Research, Education, and Clinical Center, West Los Angeles Veterans Affairs Medical Center.
The study was published online in Neurology: Clinical Practice.
Hard on the mind and body
A robust body of literature has clearly established a connection between ACEs, which include physical and emotional abuse, neglect, and household dysfunction, and negative physical health outcomes across the lifespan. These include stroke, dementia, diabetes, cancer, cardiovascular disease, autoimmune disorders, hypertension, and premature death as well as psychosocial health outcomes such as anxiety, depression, substance use, and suicide.
However, until now, the effects of childhood trauma have not been evaluated in a PD population.
As part of the MVP study, 712 adults with PD responded to an online survey asking about childhood trauma.
As anticipated, patients with the least reported childhood trauma reported the highest current QOL and lowest patient-reported motor and nonmotor symptom burden compared with peers with higher reported childhood trauma, the researchers reported.
PD symptom burden increased and QOL decreased as the number of ACEs increased.
Patients with ACE scores of 4 or higher reported greater PD symptom severity for 45% of the variables assessed, including apathy, muscle pain, daytime sleepiness, restless leg syndrome, depression, fatigue, comprehension, and anxiety (P < .05), compared with peers with trauma scores of 0.
Limitations of the study included the cross-sectional nature, which prevents making any causal determinations. Also, the ACE questionnaire, because it is self-reported and a retrospective collection of data, introduces the risk for recall bias. In addition, 65% of respondents were women, and racial and ethnic minority groups were not well represented.
Looking ahead, Dr. Subramanian and coauthors believe future research should “attempt to include more diverse populations, attempt improve the response rate of these sensitive questions and, most importantly, determine whether the adverse outcomes associated with childhood trauma can be mitigated with lifestyle modification, psychosocial support, and intervention in adulthood.”
“As a trauma-informed approach, something sorely lacking yet needed in the field of movement disorders, clinicians can proactively screen for ACEs while being mindful to avoid retraumatization,” they suggested. “They can begin to identify how ACEs may physiologically contribute to PD symptom and focus on targeting appropriate interventions that may improve outcomes.”
Life experiences matter
In a comment, Michael S. Okun, MD, medical advisor, Parkinson’s Foundation, and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said that “the idea that childhood trauma could be associated with a mild increase in severity of Parkinson’s symptoms such as apathy, pain, sleepiness and depression is fascinating.”
“We should however temper our enthusiasm for the results of this study because they were obtained through a direct patient survey, and not collected from large well characterized medical database,” Dr. Okun said.
He added” “If the data on childhood trauma and Parkinson’s can be replicated, we must ask why this could be?
“For Parkinson clinicians this as a reminder of how important obtaining a complete life history can be when strategizing on a plan to reduce motor and nonmotor Parkinson symptoms. Life experiences matter and can impact symptoms,” Dr. Okun said.
The MVP study was initiated with support of the National Center for Complementary and Integrative Health. The ongoing data collection has been supported by a donation from Sondra and Bill Fondren. Dr. Subramanian and Dr. Okun disclosed no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
new research shows.
Results of the first study to evaluate the relationship between childhood trauma and PD investigators found that the relationship appears to be dose dependent. Patients with PD who reported more than one ACE all experienced a statistically significant decrease in QOL, and for each additional ACE, there was significant worsening of motor symptoms.
This study supports a recent-call to-action paper in JAMA Neurology encouraging adoption of “trauma-informed neurology,” study investigator Indu Subramanian, MD, clinical professor, department of neurology, University of California, Los Angeles, said in an interview.
“We need to start asking about ACEs in everyone. It should be part of our medical intake,” said Dr. Subramanian, who is also the director of the Southwest Parkinson’s Disease Research, Education, and Clinical Center, West Los Angeles Veterans Affairs Medical Center.
The study was published online in Neurology: Clinical Practice.
Hard on the mind and body
A robust body of literature has clearly established a connection between ACEs, which include physical and emotional abuse, neglect, and household dysfunction, and negative physical health outcomes across the lifespan. These include stroke, dementia, diabetes, cancer, cardiovascular disease, autoimmune disorders, hypertension, and premature death as well as psychosocial health outcomes such as anxiety, depression, substance use, and suicide.
However, until now, the effects of childhood trauma have not been evaluated in a PD population.
As part of the MVP study, 712 adults with PD responded to an online survey asking about childhood trauma.
As anticipated, patients with the least reported childhood trauma reported the highest current QOL and lowest patient-reported motor and nonmotor symptom burden compared with peers with higher reported childhood trauma, the researchers reported.
PD symptom burden increased and QOL decreased as the number of ACEs increased.
Patients with ACE scores of 4 or higher reported greater PD symptom severity for 45% of the variables assessed, including apathy, muscle pain, daytime sleepiness, restless leg syndrome, depression, fatigue, comprehension, and anxiety (P < .05), compared with peers with trauma scores of 0.
Limitations of the study included the cross-sectional nature, which prevents making any causal determinations. Also, the ACE questionnaire, because it is self-reported and a retrospective collection of data, introduces the risk for recall bias. In addition, 65% of respondents were women, and racial and ethnic minority groups were not well represented.
Looking ahead, Dr. Subramanian and coauthors believe future research should “attempt to include more diverse populations, attempt improve the response rate of these sensitive questions and, most importantly, determine whether the adverse outcomes associated with childhood trauma can be mitigated with lifestyle modification, psychosocial support, and intervention in adulthood.”
“As a trauma-informed approach, something sorely lacking yet needed in the field of movement disorders, clinicians can proactively screen for ACEs while being mindful to avoid retraumatization,” they suggested. “They can begin to identify how ACEs may physiologically contribute to PD symptom and focus on targeting appropriate interventions that may improve outcomes.”
Life experiences matter
In a comment, Michael S. Okun, MD, medical advisor, Parkinson’s Foundation, and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said that “the idea that childhood trauma could be associated with a mild increase in severity of Parkinson’s symptoms such as apathy, pain, sleepiness and depression is fascinating.”
“We should however temper our enthusiasm for the results of this study because they were obtained through a direct patient survey, and not collected from large well characterized medical database,” Dr. Okun said.
He added” “If the data on childhood trauma and Parkinson’s can be replicated, we must ask why this could be?
“For Parkinson clinicians this as a reminder of how important obtaining a complete life history can be when strategizing on a plan to reduce motor and nonmotor Parkinson symptoms. Life experiences matter and can impact symptoms,” Dr. Okun said.
The MVP study was initiated with support of the National Center for Complementary and Integrative Health. The ongoing data collection has been supported by a donation from Sondra and Bill Fondren. Dr. Subramanian and Dr. Okun disclosed no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
new research shows.
Results of the first study to evaluate the relationship between childhood trauma and PD investigators found that the relationship appears to be dose dependent. Patients with PD who reported more than one ACE all experienced a statistically significant decrease in QOL, and for each additional ACE, there was significant worsening of motor symptoms.
This study supports a recent-call to-action paper in JAMA Neurology encouraging adoption of “trauma-informed neurology,” study investigator Indu Subramanian, MD, clinical professor, department of neurology, University of California, Los Angeles, said in an interview.
“We need to start asking about ACEs in everyone. It should be part of our medical intake,” said Dr. Subramanian, who is also the director of the Southwest Parkinson’s Disease Research, Education, and Clinical Center, West Los Angeles Veterans Affairs Medical Center.
The study was published online in Neurology: Clinical Practice.
Hard on the mind and body
A robust body of literature has clearly established a connection between ACEs, which include physical and emotional abuse, neglect, and household dysfunction, and negative physical health outcomes across the lifespan. These include stroke, dementia, diabetes, cancer, cardiovascular disease, autoimmune disorders, hypertension, and premature death as well as psychosocial health outcomes such as anxiety, depression, substance use, and suicide.
However, until now, the effects of childhood trauma have not been evaluated in a PD population.
As part of the MVP study, 712 adults with PD responded to an online survey asking about childhood trauma.
As anticipated, patients with the least reported childhood trauma reported the highest current QOL and lowest patient-reported motor and nonmotor symptom burden compared with peers with higher reported childhood trauma, the researchers reported.
PD symptom burden increased and QOL decreased as the number of ACEs increased.
Patients with ACE scores of 4 or higher reported greater PD symptom severity for 45% of the variables assessed, including apathy, muscle pain, daytime sleepiness, restless leg syndrome, depression, fatigue, comprehension, and anxiety (P < .05), compared with peers with trauma scores of 0.
Limitations of the study included the cross-sectional nature, which prevents making any causal determinations. Also, the ACE questionnaire, because it is self-reported and a retrospective collection of data, introduces the risk for recall bias. In addition, 65% of respondents were women, and racial and ethnic minority groups were not well represented.
Looking ahead, Dr. Subramanian and coauthors believe future research should “attempt to include more diverse populations, attempt improve the response rate of these sensitive questions and, most importantly, determine whether the adverse outcomes associated with childhood trauma can be mitigated with lifestyle modification, psychosocial support, and intervention in adulthood.”
“As a trauma-informed approach, something sorely lacking yet needed in the field of movement disorders, clinicians can proactively screen for ACEs while being mindful to avoid retraumatization,” they suggested. “They can begin to identify how ACEs may physiologically contribute to PD symptom and focus on targeting appropriate interventions that may improve outcomes.”
Life experiences matter
In a comment, Michael S. Okun, MD, medical advisor, Parkinson’s Foundation, and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said that “the idea that childhood trauma could be associated with a mild increase in severity of Parkinson’s symptoms such as apathy, pain, sleepiness and depression is fascinating.”
“We should however temper our enthusiasm for the results of this study because they were obtained through a direct patient survey, and not collected from large well characterized medical database,” Dr. Okun said.
He added” “If the data on childhood trauma and Parkinson’s can be replicated, we must ask why this could be?
“For Parkinson clinicians this as a reminder of how important obtaining a complete life history can be when strategizing on a plan to reduce motor and nonmotor Parkinson symptoms. Life experiences matter and can impact symptoms,” Dr. Okun said.
The MVP study was initiated with support of the National Center for Complementary and Integrative Health. The ongoing data collection has been supported by a donation from Sondra and Bill Fondren. Dr. Subramanian and Dr. Okun disclosed no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY: CLINICAL PRACTICE
Physician pleads guilty to 52 counts in opioid scheme
Jeffrey B. Sutton, DO, a neuromuscular medicine specialist, pled guilty on January 30 in federal court to 31 counts of illegally prescribing opioids and other controlled substances, 1 count of illegally distributing controlled substances, and 20 counts of health care fraud.
Prosecutors said Dr. Sutton admitted that he ignored warnings from prescription drug management organizations, insurers, and state authorities that he was prescribing excessively high dosages of opioids.
Dr. Sutton also admitted to ignoring patient requests to lower dosages and that he also ignored signs that patients were selling prescribed medications or otherwise engaging in illicit activity, including violations of a “pain management agreement” that he required them to sign.
The fraud counts pertained to Dr. Sutton billing Medicare, Medicaid, and other insurers for medically unnecessary visits that he required of patients so that he could prescribe inappropriate or unnecessary opioids.
In the charging document shared with this news organization, prosecutors said Dr. Sutton had sex with at least three patients, including during office visits and outside of the office. Occasionally, the physician would give opioids or other controlled substances – often benzodiazepines – to these patients, without a prescription or valid medical need.
Dr. Sutton escalated the dosage for one of those patients, even as the subjective pain score did not improve and when the patient’s urine tests showed the presence of THC and buprenorphine, but not any of the prescribed medications.
Another patient came to Dr. Sutton in 2007 with a warning that she had a history of “narcotic-seeking” behavior and diagnoses of depression, anxiety, paranoid schizophrenia, and obsessive-compulsive disorder.
The patient was hospitalized in 2018 for complications from benzodiazepine use (prescribed by Dr. Sutton). She weighed 80 pounds at the time. Dr. Sutton continued to prescribe benzodiazepines and extreme doses of opioids – in excess of 2,000 morphine equivalent dose – “despite recognizing and documenting repeated instances of noncompliance with treatment for psychiatric conditions, and despite the known contraindications of long-term opioid use for patients with these mental illnesses,” according to the charging document.
Dr. Sutton continued to prescribe opioids despite two hospitalizations for overdoses, more than 20 failed urine drug screens that showed presence of illicit drugs such as cocaine, and documented excessive use of alprazolam (Xanax) and methadone.
The physician surrendered his Drug Enforcement Administration Certificate of Registration of Controlled Substances Privileges in February 2022 “as an indication of your good faith in desiring to remedy any incorrect or unlawful practices on your part,” according to a letter to Dr. Sutton from the State Medical Board of Ohio. In that September 2022 letter, the Board notified Dr. Sutton of its intention to possibly suspend or revoke his license.
Dr. Sutton did not request a hearing, and the Board permanently revoked his medical license on January 16.
The court will sentence Dr. Sutton on May 23, according to a report by WFMJ.
A version of this article originally appeared on Medscape.com.
Jeffrey B. Sutton, DO, a neuromuscular medicine specialist, pled guilty on January 30 in federal court to 31 counts of illegally prescribing opioids and other controlled substances, 1 count of illegally distributing controlled substances, and 20 counts of health care fraud.
Prosecutors said Dr. Sutton admitted that he ignored warnings from prescription drug management organizations, insurers, and state authorities that he was prescribing excessively high dosages of opioids.
Dr. Sutton also admitted to ignoring patient requests to lower dosages and that he also ignored signs that patients were selling prescribed medications or otherwise engaging in illicit activity, including violations of a “pain management agreement” that he required them to sign.
The fraud counts pertained to Dr. Sutton billing Medicare, Medicaid, and other insurers for medically unnecessary visits that he required of patients so that he could prescribe inappropriate or unnecessary opioids.
In the charging document shared with this news organization, prosecutors said Dr. Sutton had sex with at least three patients, including during office visits and outside of the office. Occasionally, the physician would give opioids or other controlled substances – often benzodiazepines – to these patients, without a prescription or valid medical need.
Dr. Sutton escalated the dosage for one of those patients, even as the subjective pain score did not improve and when the patient’s urine tests showed the presence of THC and buprenorphine, but not any of the prescribed medications.
Another patient came to Dr. Sutton in 2007 with a warning that she had a history of “narcotic-seeking” behavior and diagnoses of depression, anxiety, paranoid schizophrenia, and obsessive-compulsive disorder.
The patient was hospitalized in 2018 for complications from benzodiazepine use (prescribed by Dr. Sutton). She weighed 80 pounds at the time. Dr. Sutton continued to prescribe benzodiazepines and extreme doses of opioids – in excess of 2,000 morphine equivalent dose – “despite recognizing and documenting repeated instances of noncompliance with treatment for psychiatric conditions, and despite the known contraindications of long-term opioid use for patients with these mental illnesses,” according to the charging document.
Dr. Sutton continued to prescribe opioids despite two hospitalizations for overdoses, more than 20 failed urine drug screens that showed presence of illicit drugs such as cocaine, and documented excessive use of alprazolam (Xanax) and methadone.
The physician surrendered his Drug Enforcement Administration Certificate of Registration of Controlled Substances Privileges in February 2022 “as an indication of your good faith in desiring to remedy any incorrect or unlawful practices on your part,” according to a letter to Dr. Sutton from the State Medical Board of Ohio. In that September 2022 letter, the Board notified Dr. Sutton of its intention to possibly suspend or revoke his license.
Dr. Sutton did not request a hearing, and the Board permanently revoked his medical license on January 16.
The court will sentence Dr. Sutton on May 23, according to a report by WFMJ.
A version of this article originally appeared on Medscape.com.
Jeffrey B. Sutton, DO, a neuromuscular medicine specialist, pled guilty on January 30 in federal court to 31 counts of illegally prescribing opioids and other controlled substances, 1 count of illegally distributing controlled substances, and 20 counts of health care fraud.
Prosecutors said Dr. Sutton admitted that he ignored warnings from prescription drug management organizations, insurers, and state authorities that he was prescribing excessively high dosages of opioids.
Dr. Sutton also admitted to ignoring patient requests to lower dosages and that he also ignored signs that patients were selling prescribed medications or otherwise engaging in illicit activity, including violations of a “pain management agreement” that he required them to sign.
The fraud counts pertained to Dr. Sutton billing Medicare, Medicaid, and other insurers for medically unnecessary visits that he required of patients so that he could prescribe inappropriate or unnecessary opioids.
In the charging document shared with this news organization, prosecutors said Dr. Sutton had sex with at least three patients, including during office visits and outside of the office. Occasionally, the physician would give opioids or other controlled substances – often benzodiazepines – to these patients, without a prescription or valid medical need.
Dr. Sutton escalated the dosage for one of those patients, even as the subjective pain score did not improve and when the patient’s urine tests showed the presence of THC and buprenorphine, but not any of the prescribed medications.
Another patient came to Dr. Sutton in 2007 with a warning that she had a history of “narcotic-seeking” behavior and diagnoses of depression, anxiety, paranoid schizophrenia, and obsessive-compulsive disorder.
The patient was hospitalized in 2018 for complications from benzodiazepine use (prescribed by Dr. Sutton). She weighed 80 pounds at the time. Dr. Sutton continued to prescribe benzodiazepines and extreme doses of opioids – in excess of 2,000 morphine equivalent dose – “despite recognizing and documenting repeated instances of noncompliance with treatment for psychiatric conditions, and despite the known contraindications of long-term opioid use for patients with these mental illnesses,” according to the charging document.
Dr. Sutton continued to prescribe opioids despite two hospitalizations for overdoses, more than 20 failed urine drug screens that showed presence of illicit drugs such as cocaine, and documented excessive use of alprazolam (Xanax) and methadone.
The physician surrendered his Drug Enforcement Administration Certificate of Registration of Controlled Substances Privileges in February 2022 “as an indication of your good faith in desiring to remedy any incorrect or unlawful practices on your part,” according to a letter to Dr. Sutton from the State Medical Board of Ohio. In that September 2022 letter, the Board notified Dr. Sutton of its intention to possibly suspend or revoke his license.
Dr. Sutton did not request a hearing, and the Board permanently revoked his medical license on January 16.
The court will sentence Dr. Sutton on May 23, according to a report by WFMJ.
A version of this article originally appeared on Medscape.com.
What’s new in brain health?
This transcript has been edited for clarity.
Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany.
Treatment of tension-type headache
I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.
A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.
The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.
In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
Headache after COVID-19
The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.
SSRIs during COVID-19 infection
The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.
Preventing dementia with antihypertensive treatment
The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.
Antiplatelet therapy
The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.
Regular exercise in Parkinson’s disease
The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.
Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.
This transcript has been edited for clarity.
Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany.
Treatment of tension-type headache
I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.
A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.
The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.
In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
Headache after COVID-19
The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.
SSRIs during COVID-19 infection
The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.
Preventing dementia with antihypertensive treatment
The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.
Antiplatelet therapy
The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.
Regular exercise in Parkinson’s disease
The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.
Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.
This transcript has been edited for clarity.
Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany.
Treatment of tension-type headache
I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.
A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.
The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.
In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
Headache after COVID-19
The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.
SSRIs during COVID-19 infection
The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.
Preventing dementia with antihypertensive treatment
The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.
Antiplatelet therapy
The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.
Regular exercise in Parkinson’s disease
The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.
Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.
Three wild technologies about to change health care
When I was a child, I watched syndicated episodes of the original “Star Trek.” I was dazzled by the space travel, sure, but also the medical technology.
A handheld “tricorder” detected diseases, while an intramuscular injector (“hypospray”) could treat them. Sickbay “biobeds” came with real-time health monitors that looked futuristic at the time but seem primitive today.
Such visions inspired a lot of us kids to pursue science. Little did we know the real-life advances many of us would see in our lifetimes.
Artificial intelligence helping to spot disease, robots performing surgery, even video calls between doctor and patient – all these once sounded fantastical but now happen in clinical care.
Now, in the 23rd year of the 21st century, you might not believe wht we’ll be capable of next. Three especially wild examples are moving closer to clinical reality.
Human hibernation
Captain America, Han Solo, and “Star Trek” villain Khan – all were preserved at low temperatures and then revived, waking up alive and well months, decades, or centuries later. These are fictional examples, to be sure, but the science they’re rooted in is real.
(In one extreme case, a climber survived after almost 9 hours of efforts to revive him.)
Useful for a space traveler? Maybe not. But it’s potentially huge for someone with life-threatening injuries from a car accident or a gunshot wound.
That’s the thinking behind a breakthrough procedure that came after decades of research on pigs and dogs, now in a clinical trial. The idea: A person with massive blood loss whose heart has stopped is injected with an ice-cold fluid, cooling them from the inside, down to about 50° F.
Doctors already induce more modest hypothermia to protect the brain and other organs after cardiac arrest and during surgery on the aortic arch (the main artery carrying blood from the heart).
But this experimental procedure – called emergency preservation and resuscitation (EPR) – goes far beyond that, dramatically “decreasing the body’s need for oxygen and blood flow,” says Samuel Tisherman, MD, a trauma surgeon at the University of Maryland Medical Center and the trial’s lead researcher. This puts the patient in a state of suspended animation that “could buy time for surgeons to stop the bleeding and save more of these patients.”
The technique has been done on at least six patients, though none were reported to survive. The trial is expected to include 20 people by the time it wraps up in December, according to the listing on the U.S. clinical trials database. Though given the strict requirements for candidates (emergency trauma victims who are not likely to survive), one can’t exactly rely on a set schedule.
Still, the technology is promising. Someday we may even use it to keep patients in suspended animation for months or years, experts predict, helping astronauts through decades-long spaceflights, or stalling death in sick patients awaiting a cure.
Artificial womb
Another sci-fi classic: growing human babies outside the womb. Think the fetus fields from “The Matrix,” or the frozen embryos in “Alien: Covenant.”
In 1923, British biologist J.B.S. Haldane coined a term for that – ectogenesis. He predicted that 70% of pregnancies would take place, from fertilization to birth, in artificial wombs by 2074. That many seems unlikely, but the timeline is on track.
Developing an embryo outside the womb is already routine in in vitro fertilization. And technology enables preterm babies to survive through much of the second half of gestation. Normal human pregnancy is 40 weeks, and the youngest preterm baby ever to survive was 21 weeks and 1 day old, just a few days younger than a smattering of others who lived.
The biggest obstacle for babies younger than that is lung viability. Mechanical ventilation can damage the lungs and lead to a chronic (sometimes fatal) lung disease known as bronchopulmonary dysplasia. Avoiding this would mean figuring out a way to maintain fetal circulation – the intricate system that delivers oxygenated blood from the placenta to the fetus via the umbilical cord. Researchers at Children’s Hospital of Philadelphia have done this using a fetal lamb.
The key to their invention is a substitute placenta: an oxygenator connected to the lamb’s umbilical cord. Tubes inserted through the umbilical vein and arteries carry oxygenated blood from the “placenta” to the fetus, and deoxygenated blood back out. The lamb resides in an artificial, fluid-filled amniotic sac until its lungs and other organs are developed.
Fertility treatment could benefit, too. “An artificial womb may substitute in situations in which a gestational carrier – surrogate – is indicated,” says Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health and Science University, Portland. (Dr. Amato is not involved in the CHOP research.) For example: when the mother is missing a uterus or can’t carry a pregnancy safely.
No date is set for clinical trials yet. But according to the research, the main difference between human and lamb may come down to size. A lamb’s umbilical vessels are larger, so feeding in a tube is easier. With today’s advances in miniaturizing surgical methods, that seems like a challenge scientists can overcome.
Messenger RNA therapeutics
Back to “Star Trek.” The hypospray injector’s contents could cure just about any disease, even one newly discovered on a strange planet. That’s not unlike messenger RNA (mRNA) technology, a breakthrough that enabled scientists to quickly develop some of the first COVID-19 vaccines.
But vaccines are just the beginning of what this technology can do.
A whole field of immunotherapy is emerging that uses mRNA to deliver instructions to produce chimeric antigen receptor–modified immune cells (CAR-modified immune cells). These cells are engineered to target diseased cells and tissues, like cancer cells and harmful fibroblasts (scar tissue) that promote fibrosis in, for example, the heart and lungs.
The field is bursting with rodent research, and clinical trials have started for treating some advanced-stage malignancies.
Actual clinical use may be years away, but if all goes well, these medicines could help treat or even cure the core medical problems facing humanity. We’re talking cancer, heart disease, neurodegenerative disease – transforming one therapy into another by simply changing the mRNA’s “nucleotide sequence,” the blueprint containing instructions telling it what to do, and what disease to attack.
As this technology matures, we may start to feel as if we’re really on “Star Trek,” where Dr. Leonard “Bones” McCoy pulls out the same device to treat just about every disease or injury.
A version of this article first appeared on WebMD.com.
When I was a child, I watched syndicated episodes of the original “Star Trek.” I was dazzled by the space travel, sure, but also the medical technology.
A handheld “tricorder” detected diseases, while an intramuscular injector (“hypospray”) could treat them. Sickbay “biobeds” came with real-time health monitors that looked futuristic at the time but seem primitive today.
Such visions inspired a lot of us kids to pursue science. Little did we know the real-life advances many of us would see in our lifetimes.
Artificial intelligence helping to spot disease, robots performing surgery, even video calls between doctor and patient – all these once sounded fantastical but now happen in clinical care.
Now, in the 23rd year of the 21st century, you might not believe wht we’ll be capable of next. Three especially wild examples are moving closer to clinical reality.
Human hibernation
Captain America, Han Solo, and “Star Trek” villain Khan – all were preserved at low temperatures and then revived, waking up alive and well months, decades, or centuries later. These are fictional examples, to be sure, but the science they’re rooted in is real.
(In one extreme case, a climber survived after almost 9 hours of efforts to revive him.)
Useful for a space traveler? Maybe not. But it’s potentially huge for someone with life-threatening injuries from a car accident or a gunshot wound.
That’s the thinking behind a breakthrough procedure that came after decades of research on pigs and dogs, now in a clinical trial. The idea: A person with massive blood loss whose heart has stopped is injected with an ice-cold fluid, cooling them from the inside, down to about 50° F.
Doctors already induce more modest hypothermia to protect the brain and other organs after cardiac arrest and during surgery on the aortic arch (the main artery carrying blood from the heart).
But this experimental procedure – called emergency preservation and resuscitation (EPR) – goes far beyond that, dramatically “decreasing the body’s need for oxygen and blood flow,” says Samuel Tisherman, MD, a trauma surgeon at the University of Maryland Medical Center and the trial’s lead researcher. This puts the patient in a state of suspended animation that “could buy time for surgeons to stop the bleeding and save more of these patients.”
The technique has been done on at least six patients, though none were reported to survive. The trial is expected to include 20 people by the time it wraps up in December, according to the listing on the U.S. clinical trials database. Though given the strict requirements for candidates (emergency trauma victims who are not likely to survive), one can’t exactly rely on a set schedule.
Still, the technology is promising. Someday we may even use it to keep patients in suspended animation for months or years, experts predict, helping astronauts through decades-long spaceflights, or stalling death in sick patients awaiting a cure.
Artificial womb
Another sci-fi classic: growing human babies outside the womb. Think the fetus fields from “The Matrix,” or the frozen embryos in “Alien: Covenant.”
In 1923, British biologist J.B.S. Haldane coined a term for that – ectogenesis. He predicted that 70% of pregnancies would take place, from fertilization to birth, in artificial wombs by 2074. That many seems unlikely, but the timeline is on track.
Developing an embryo outside the womb is already routine in in vitro fertilization. And technology enables preterm babies to survive through much of the second half of gestation. Normal human pregnancy is 40 weeks, and the youngest preterm baby ever to survive was 21 weeks and 1 day old, just a few days younger than a smattering of others who lived.
The biggest obstacle for babies younger than that is lung viability. Mechanical ventilation can damage the lungs and lead to a chronic (sometimes fatal) lung disease known as bronchopulmonary dysplasia. Avoiding this would mean figuring out a way to maintain fetal circulation – the intricate system that delivers oxygenated blood from the placenta to the fetus via the umbilical cord. Researchers at Children’s Hospital of Philadelphia have done this using a fetal lamb.
The key to their invention is a substitute placenta: an oxygenator connected to the lamb’s umbilical cord. Tubes inserted through the umbilical vein and arteries carry oxygenated blood from the “placenta” to the fetus, and deoxygenated blood back out. The lamb resides in an artificial, fluid-filled amniotic sac until its lungs and other organs are developed.
Fertility treatment could benefit, too. “An artificial womb may substitute in situations in which a gestational carrier – surrogate – is indicated,” says Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health and Science University, Portland. (Dr. Amato is not involved in the CHOP research.) For example: when the mother is missing a uterus or can’t carry a pregnancy safely.
No date is set for clinical trials yet. But according to the research, the main difference between human and lamb may come down to size. A lamb’s umbilical vessels are larger, so feeding in a tube is easier. With today’s advances in miniaturizing surgical methods, that seems like a challenge scientists can overcome.
Messenger RNA therapeutics
Back to “Star Trek.” The hypospray injector’s contents could cure just about any disease, even one newly discovered on a strange planet. That’s not unlike messenger RNA (mRNA) technology, a breakthrough that enabled scientists to quickly develop some of the first COVID-19 vaccines.
But vaccines are just the beginning of what this technology can do.
A whole field of immunotherapy is emerging that uses mRNA to deliver instructions to produce chimeric antigen receptor–modified immune cells (CAR-modified immune cells). These cells are engineered to target diseased cells and tissues, like cancer cells and harmful fibroblasts (scar tissue) that promote fibrosis in, for example, the heart and lungs.
The field is bursting with rodent research, and clinical trials have started for treating some advanced-stage malignancies.
Actual clinical use may be years away, but if all goes well, these medicines could help treat or even cure the core medical problems facing humanity. We’re talking cancer, heart disease, neurodegenerative disease – transforming one therapy into another by simply changing the mRNA’s “nucleotide sequence,” the blueprint containing instructions telling it what to do, and what disease to attack.
As this technology matures, we may start to feel as if we’re really on “Star Trek,” where Dr. Leonard “Bones” McCoy pulls out the same device to treat just about every disease or injury.
A version of this article first appeared on WebMD.com.
When I was a child, I watched syndicated episodes of the original “Star Trek.” I was dazzled by the space travel, sure, but also the medical technology.
A handheld “tricorder” detected diseases, while an intramuscular injector (“hypospray”) could treat them. Sickbay “biobeds” came with real-time health monitors that looked futuristic at the time but seem primitive today.
Such visions inspired a lot of us kids to pursue science. Little did we know the real-life advances many of us would see in our lifetimes.
Artificial intelligence helping to spot disease, robots performing surgery, even video calls between doctor and patient – all these once sounded fantastical but now happen in clinical care.
Now, in the 23rd year of the 21st century, you might not believe wht we’ll be capable of next. Three especially wild examples are moving closer to clinical reality.
Human hibernation
Captain America, Han Solo, and “Star Trek” villain Khan – all were preserved at low temperatures and then revived, waking up alive and well months, decades, or centuries later. These are fictional examples, to be sure, but the science they’re rooted in is real.
(In one extreme case, a climber survived after almost 9 hours of efforts to revive him.)
Useful for a space traveler? Maybe not. But it’s potentially huge for someone with life-threatening injuries from a car accident or a gunshot wound.
That’s the thinking behind a breakthrough procedure that came after decades of research on pigs and dogs, now in a clinical trial. The idea: A person with massive blood loss whose heart has stopped is injected with an ice-cold fluid, cooling them from the inside, down to about 50° F.
Doctors already induce more modest hypothermia to protect the brain and other organs after cardiac arrest and during surgery on the aortic arch (the main artery carrying blood from the heart).
But this experimental procedure – called emergency preservation and resuscitation (EPR) – goes far beyond that, dramatically “decreasing the body’s need for oxygen and blood flow,” says Samuel Tisherman, MD, a trauma surgeon at the University of Maryland Medical Center and the trial’s lead researcher. This puts the patient in a state of suspended animation that “could buy time for surgeons to stop the bleeding and save more of these patients.”
The technique has been done on at least six patients, though none were reported to survive. The trial is expected to include 20 people by the time it wraps up in December, according to the listing on the U.S. clinical trials database. Though given the strict requirements for candidates (emergency trauma victims who are not likely to survive), one can’t exactly rely on a set schedule.
Still, the technology is promising. Someday we may even use it to keep patients in suspended animation for months or years, experts predict, helping astronauts through decades-long spaceflights, or stalling death in sick patients awaiting a cure.
Artificial womb
Another sci-fi classic: growing human babies outside the womb. Think the fetus fields from “The Matrix,” or the frozen embryos in “Alien: Covenant.”
In 1923, British biologist J.B.S. Haldane coined a term for that – ectogenesis. He predicted that 70% of pregnancies would take place, from fertilization to birth, in artificial wombs by 2074. That many seems unlikely, but the timeline is on track.
Developing an embryo outside the womb is already routine in in vitro fertilization. And technology enables preterm babies to survive through much of the second half of gestation. Normal human pregnancy is 40 weeks, and the youngest preterm baby ever to survive was 21 weeks and 1 day old, just a few days younger than a smattering of others who lived.
The biggest obstacle for babies younger than that is lung viability. Mechanical ventilation can damage the lungs and lead to a chronic (sometimes fatal) lung disease known as bronchopulmonary dysplasia. Avoiding this would mean figuring out a way to maintain fetal circulation – the intricate system that delivers oxygenated blood from the placenta to the fetus via the umbilical cord. Researchers at Children’s Hospital of Philadelphia have done this using a fetal lamb.
The key to their invention is a substitute placenta: an oxygenator connected to the lamb’s umbilical cord. Tubes inserted through the umbilical vein and arteries carry oxygenated blood from the “placenta” to the fetus, and deoxygenated blood back out. The lamb resides in an artificial, fluid-filled amniotic sac until its lungs and other organs are developed.
Fertility treatment could benefit, too. “An artificial womb may substitute in situations in which a gestational carrier – surrogate – is indicated,” says Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health and Science University, Portland. (Dr. Amato is not involved in the CHOP research.) For example: when the mother is missing a uterus or can’t carry a pregnancy safely.
No date is set for clinical trials yet. But according to the research, the main difference between human and lamb may come down to size. A lamb’s umbilical vessels are larger, so feeding in a tube is easier. With today’s advances in miniaturizing surgical methods, that seems like a challenge scientists can overcome.
Messenger RNA therapeutics
Back to “Star Trek.” The hypospray injector’s contents could cure just about any disease, even one newly discovered on a strange planet. That’s not unlike messenger RNA (mRNA) technology, a breakthrough that enabled scientists to quickly develop some of the first COVID-19 vaccines.
But vaccines are just the beginning of what this technology can do.
A whole field of immunotherapy is emerging that uses mRNA to deliver instructions to produce chimeric antigen receptor–modified immune cells (CAR-modified immune cells). These cells are engineered to target diseased cells and tissues, like cancer cells and harmful fibroblasts (scar tissue) that promote fibrosis in, for example, the heart and lungs.
The field is bursting with rodent research, and clinical trials have started for treating some advanced-stage malignancies.
Actual clinical use may be years away, but if all goes well, these medicines could help treat or even cure the core medical problems facing humanity. We’re talking cancer, heart disease, neurodegenerative disease – transforming one therapy into another by simply changing the mRNA’s “nucleotide sequence,” the blueprint containing instructions telling it what to do, and what disease to attack.
As this technology matures, we may start to feel as if we’re really on “Star Trek,” where Dr. Leonard “Bones” McCoy pulls out the same device to treat just about every disease or injury.
A version of this article first appeared on WebMD.com.
High drug costs exclude most neurology patients from cutting-edge treatment
, new research shows.
“Our study of people with neurologic conditions found that fewer than 20% were being treated with new medications,” study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.
“For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease,” Dr. Callaghan said.
The study was published online in Neurology.
Most expensive drugs
Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 with those for existing guideline-supported medications for treating 11 neurologic conditions.
The new drugs included:
- erenumab, fremanezumab, and galcanezumab for migraine.
- ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS).
- pimavanserin and safinamide for Parkinson’s disease.
- droxidopa for orthostatic hypertension.
- eculizumab for myasthenia gravis (MG).
- edaravone for amyotrophic lateral sclerosis (ALS).
- deutetrabenazine and valbenazine for Huntington’s disease and tardive dyskinesia.
- patisiran and inotersen for transthyretin amyloidosis (ATTR).
- eteplirsen and deflazacort for Duchenne disease.
- nusinersen for spinal muscular atrophy (SMA).
Utilization of new drugs was modest – they accounted for one in five prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers noted.
Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.
The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.
“For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared with existing guideline-supported medications,” the authors reported.
They noted that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.
Given that most of the new neurologic agents offer little advantage compared with existing treatments – exceptions being new drugs for SMA and ATTR – drug costs should be a key consideration in prescribing decisions, Dr. Callaghan and colleagues concluded.
One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.
Revolution in neurotherapeutics
“We are living in a time when new treatments bring hope to people with neurologic diseases and disorders,” Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.
“However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them,” Dr. Avitzur added.
Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, department of neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting < 200,000 Americans).
“This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease-modifying therapy may be, if a patient cannot afford the cost, it doesn’t work,” Dr. Smith wrote.
He added that neurologists must be “diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point-of-care tools to accurately estimate each patient’s potential financial toxicity including RTBT [real-time benefit tools].
“Neurologists’ primary obligation is to the individual patient, but we are also compelled to support access to high-quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success,” Dr. Smith added.
The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Dr. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Dr. Smith has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
“Our study of people with neurologic conditions found that fewer than 20% were being treated with new medications,” study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.
“For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease,” Dr. Callaghan said.
The study was published online in Neurology.
Most expensive drugs
Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 with those for existing guideline-supported medications for treating 11 neurologic conditions.
The new drugs included:
- erenumab, fremanezumab, and galcanezumab for migraine.
- ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS).
- pimavanserin and safinamide for Parkinson’s disease.
- droxidopa for orthostatic hypertension.
- eculizumab for myasthenia gravis (MG).
- edaravone for amyotrophic lateral sclerosis (ALS).
- deutetrabenazine and valbenazine for Huntington’s disease and tardive dyskinesia.
- patisiran and inotersen for transthyretin amyloidosis (ATTR).
- eteplirsen and deflazacort for Duchenne disease.
- nusinersen for spinal muscular atrophy (SMA).
Utilization of new drugs was modest – they accounted for one in five prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers noted.
Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.
The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.
“For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared with existing guideline-supported medications,” the authors reported.
They noted that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.
Given that most of the new neurologic agents offer little advantage compared with existing treatments – exceptions being new drugs for SMA and ATTR – drug costs should be a key consideration in prescribing decisions, Dr. Callaghan and colleagues concluded.
One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.
Revolution in neurotherapeutics
“We are living in a time when new treatments bring hope to people with neurologic diseases and disorders,” Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.
“However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them,” Dr. Avitzur added.
Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, department of neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting < 200,000 Americans).
“This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease-modifying therapy may be, if a patient cannot afford the cost, it doesn’t work,” Dr. Smith wrote.
He added that neurologists must be “diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point-of-care tools to accurately estimate each patient’s potential financial toxicity including RTBT [real-time benefit tools].
“Neurologists’ primary obligation is to the individual patient, but we are also compelled to support access to high-quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success,” Dr. Smith added.
The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Dr. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Dr. Smith has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
“Our study of people with neurologic conditions found that fewer than 20% were being treated with new medications,” study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.
“For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease,” Dr. Callaghan said.
The study was published online in Neurology.
Most expensive drugs
Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 with those for existing guideline-supported medications for treating 11 neurologic conditions.
The new drugs included:
- erenumab, fremanezumab, and galcanezumab for migraine.
- ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS).
- pimavanserin and safinamide for Parkinson’s disease.
- droxidopa for orthostatic hypertension.
- eculizumab for myasthenia gravis (MG).
- edaravone for amyotrophic lateral sclerosis (ALS).
- deutetrabenazine and valbenazine for Huntington’s disease and tardive dyskinesia.
- patisiran and inotersen for transthyretin amyloidosis (ATTR).
- eteplirsen and deflazacort for Duchenne disease.
- nusinersen for spinal muscular atrophy (SMA).
Utilization of new drugs was modest – they accounted for one in five prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers noted.
Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.
The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.
“For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared with existing guideline-supported medications,” the authors reported.
They noted that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.
Given that most of the new neurologic agents offer little advantage compared with existing treatments – exceptions being new drugs for SMA and ATTR – drug costs should be a key consideration in prescribing decisions, Dr. Callaghan and colleagues concluded.
One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.
Revolution in neurotherapeutics
“We are living in a time when new treatments bring hope to people with neurologic diseases and disorders,” Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.
“However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them,” Dr. Avitzur added.
Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, department of neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting < 200,000 Americans).
“This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease-modifying therapy may be, if a patient cannot afford the cost, it doesn’t work,” Dr. Smith wrote.
He added that neurologists must be “diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point-of-care tools to accurately estimate each patient’s potential financial toxicity including RTBT [real-time benefit tools].
“Neurologists’ primary obligation is to the individual patient, but we are also compelled to support access to high-quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success,” Dr. Smith added.
The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Dr. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Dr. Smith has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
AAP issues clinical update to cerebral palsy guidelines
Updated clinical guidelines for the early diagnosis and management of cerebral palsy have been issued by the American Academy of Pediatrics.
Coauthored with the American Academy for Cerebral Palsy and Developmental Medicine, the report builds on new evidence for improved care and outcomes since the 2006 consensus guidelines.
Cerebral palsy, the most common neuromotor disorder of childhood, is often accompanied by cognitive impairments, epilepsy, sensory impairments, behavioral problems, communication difficulties, breathing and sleep problems, gastrointestinal and nutritional problems, and bone and orthopedic problems.
In the United States, the estimated prevalence of cerebral palsy ranges from 1.5 to 4 per 1,000 live births.
“Early identification and initiation of evidence-based motor therapies can improve outcomes by taking advantage of the neuroplasticity in the infant brain,” said the guideline authors in an executive summary.
The guideline, published in Pediatrics, is directed to primary care physicians with pediatrics, family practice, or internal medicine training. “It’s a much more comprehensive overview of the important role that primary care providers play in the lifetime care of people with cerebral palsy,” explained Garey Noritz, MD, chair of the 2021-2022 Executive Committee of the Council on Children with Disabilities. Dr. Noritz, a professor of pediatrics at Ohio State University and division chief of the complex health care program at Nationwide Children’s Hospital, both in Columbus, said: “The combined efforts of the primary care physician and specialty providers are needed to achieve the best outcomes.”
The AAP recommends that primary care pediatricians, neonatologists, and other specialists caring for hospitalized newborns recognize those at high risk of cerebral palsy, diagnose them as early as possible, and promptly refer them for therapy. Primary care physicians are advised to identify motor delays early by formalizing standardized developmental surveillance and screening at 9, 18, and 30 months, and to implement family-centered care across multiple specialists.
“If a motor disorder is suspected, primary care physicians should simultaneously begin a medical evaluation, refer to a specialist for definitive diagnosis, and to therapists for treatment,” Dr. Noritz emphasized.
“The earlier any possible movement disorder is recognized and intervention begins, the better a child can develop a gait pattern and work toward living an independent life, said Manish N. Shah, MD, associate professor of pediatric neurosurgery at the University of Texas, Houston, who was not involved in developing the guidelines.
For children in whom physical therapy and medication have not reduced leg spasticity, a minimally invasive spinal procedure can help release contracted tendons and encourage independent walking. The optimal age for selective dorsal rhizotomy is about 4 years, said Dr. Shah, who is director of the Texas Comprehensive Spasticity Center at Children’s Memorial Hermann Hospital in Houston. “You can turn these children into walkers. As adults, they can get jobs, have their own families. It’s life-changing.”
Importantly, the guidelines address the health care disparities leading to a higher prevalence of cerebral palsy in Black children and in those from families with lower socioeconomic status. “Efforts to combat racism and eliminate barriers to culturally sensitive prenatal, perinatal, and later pediatric care may help to improve outcomes for all children with cerebral palsy,” the authors said.
“Every child with cerebral palsy needs an individual plan, but only 30% or 40% are getting interventions,” said Dr. Shah. The updated guidelines could help payers rethink the 15-20 visits a year that are often approved, compared with the 2-3 visits per week that are needed for speech, physical, and occupational therapy, he pointed out.
“Financial issues often compromise the interdisciplinary and coordinated care associated with favorable outcomes in children with cerebral palsy,” said Heidi Feldman, MD, PhD, a developmental and behavioral pediatric specialist at Stanford (Calif.) Medicine Children’s Health’s Johnson Center for Pregnancy and Newborn Services. “With a new guideline, there may be greater willingness to fund these essential services.”
In the meantime, the AAP recommends that pediatricians advise families about available medical, social, and educational services, such as early intervention services, the Title V Maternal and Child Health block grant program, and special education services through the public school system.
Children with cerebral palsy need the same standardized primary care as any child, including the full schedule of recommended vaccinations and vision and hearing testing. They also need to be monitored and treated for the many problems that commonly co-occur, including chronic pain.
When secondary complications arise, the frequency of visits should increase.
Pneumonia, the leading cause of death in children and adolescents with cerebral palsy, can be prevented or minimized through immunization against respiratory diseases and screening for signs and symptoms of aspiration and sleep-disordered breathing.
The AAP also recommends that symptoms or functional declines undergo full investigation into other potential causes.
Since the sedentary lifestyle associated with cerebral palsy is now known to be related to the higher rates of cardiovascular complications in this patient population, the AAP recommends more attention be paid to physical activity and a healthy diet early in life. Pediatricians are advised to help families locate suitable opportunities for adaptive sports and recreation.
Almost 50% of children and adolescents with cerebral palsy have intellectual disability, 60%-80% have difficulty speaking, and about 25% are nonverbal. To address this, pediatricians should maximize the use of augmentative and alternative communication devices and involve experts in speech and language pathology, according to the guidelines.
“Many individuals with cerebral palsy and severe motor limitations have active, creative minds, and may need assistive technology, such as electronic talking devices, to demonstrate that mental life,” said Dr. Feldman. “Primary care clinicians should advocate for assistive technology.”
For challenging behavior, especially in the patient with limited verbal skills, potential nonbehavioral culprits such as constipation, esophageal reflux disease, and musculoskeletal or dental pain must be ruled out.
In the lead-up to adolescence, youth with cerebral palsy must be prepared for puberty, menstruation, and healthy, safe sexual relationships, much like their nonaffected peers. Since a disproportionate number of children with cerebral palsy experience neglect and physical, sexual, and emotional abuse, however, family stressors should be identified and caregivers referred for support services.
For the transition from pediatric to adult health care, the AAP recommends that structured planning begin between 12 and 14 years of age. Before transfer, the pediatrician should prepare a comprehensive medical summary with the input of the patient, parent/guardian, and pediatric subspecialists.
Without a proper handoff, “there is an increased risk of morbidity, medical complications, unnecessary emergency department visits, hospitalizations, and procedures,” the authors warned.
Transitions are likely to run more smoothly when youth are given the opportunity to understand their medical condition and be involved in decisions about their health. With this in mind, the AAP recommends that pediatricians actively discourage overprotective parents from getting in the way of their child developing “maximal independence.”
No potential conflicts of interest were disclosed by the authors, Dr. Shah, or Dr. Feldman.
*This story was updated on Nov. 28, 2022.
Updated clinical guidelines for the early diagnosis and management of cerebral palsy have been issued by the American Academy of Pediatrics.
Coauthored with the American Academy for Cerebral Palsy and Developmental Medicine, the report builds on new evidence for improved care and outcomes since the 2006 consensus guidelines.
Cerebral palsy, the most common neuromotor disorder of childhood, is often accompanied by cognitive impairments, epilepsy, sensory impairments, behavioral problems, communication difficulties, breathing and sleep problems, gastrointestinal and nutritional problems, and bone and orthopedic problems.
In the United States, the estimated prevalence of cerebral palsy ranges from 1.5 to 4 per 1,000 live births.
“Early identification and initiation of evidence-based motor therapies can improve outcomes by taking advantage of the neuroplasticity in the infant brain,” said the guideline authors in an executive summary.
The guideline, published in Pediatrics, is directed to primary care physicians with pediatrics, family practice, or internal medicine training. “It’s a much more comprehensive overview of the important role that primary care providers play in the lifetime care of people with cerebral palsy,” explained Garey Noritz, MD, chair of the 2021-2022 Executive Committee of the Council on Children with Disabilities. Dr. Noritz, a professor of pediatrics at Ohio State University and division chief of the complex health care program at Nationwide Children’s Hospital, both in Columbus, said: “The combined efforts of the primary care physician and specialty providers are needed to achieve the best outcomes.”
The AAP recommends that primary care pediatricians, neonatologists, and other specialists caring for hospitalized newborns recognize those at high risk of cerebral palsy, diagnose them as early as possible, and promptly refer them for therapy. Primary care physicians are advised to identify motor delays early by formalizing standardized developmental surveillance and screening at 9, 18, and 30 months, and to implement family-centered care across multiple specialists.
“If a motor disorder is suspected, primary care physicians should simultaneously begin a medical evaluation, refer to a specialist for definitive diagnosis, and to therapists for treatment,” Dr. Noritz emphasized.
“The earlier any possible movement disorder is recognized and intervention begins, the better a child can develop a gait pattern and work toward living an independent life, said Manish N. Shah, MD, associate professor of pediatric neurosurgery at the University of Texas, Houston, who was not involved in developing the guidelines.
For children in whom physical therapy and medication have not reduced leg spasticity, a minimally invasive spinal procedure can help release contracted tendons and encourage independent walking. The optimal age for selective dorsal rhizotomy is about 4 years, said Dr. Shah, who is director of the Texas Comprehensive Spasticity Center at Children’s Memorial Hermann Hospital in Houston. “You can turn these children into walkers. As adults, they can get jobs, have their own families. It’s life-changing.”
Importantly, the guidelines address the health care disparities leading to a higher prevalence of cerebral palsy in Black children and in those from families with lower socioeconomic status. “Efforts to combat racism and eliminate barriers to culturally sensitive prenatal, perinatal, and later pediatric care may help to improve outcomes for all children with cerebral palsy,” the authors said.
“Every child with cerebral palsy needs an individual plan, but only 30% or 40% are getting interventions,” said Dr. Shah. The updated guidelines could help payers rethink the 15-20 visits a year that are often approved, compared with the 2-3 visits per week that are needed for speech, physical, and occupational therapy, he pointed out.
“Financial issues often compromise the interdisciplinary and coordinated care associated with favorable outcomes in children with cerebral palsy,” said Heidi Feldman, MD, PhD, a developmental and behavioral pediatric specialist at Stanford (Calif.) Medicine Children’s Health’s Johnson Center for Pregnancy and Newborn Services. “With a new guideline, there may be greater willingness to fund these essential services.”
In the meantime, the AAP recommends that pediatricians advise families about available medical, social, and educational services, such as early intervention services, the Title V Maternal and Child Health block grant program, and special education services through the public school system.
Children with cerebral palsy need the same standardized primary care as any child, including the full schedule of recommended vaccinations and vision and hearing testing. They also need to be monitored and treated for the many problems that commonly co-occur, including chronic pain.
When secondary complications arise, the frequency of visits should increase.
Pneumonia, the leading cause of death in children and adolescents with cerebral palsy, can be prevented or minimized through immunization against respiratory diseases and screening for signs and symptoms of aspiration and sleep-disordered breathing.
The AAP also recommends that symptoms or functional declines undergo full investigation into other potential causes.
Since the sedentary lifestyle associated with cerebral palsy is now known to be related to the higher rates of cardiovascular complications in this patient population, the AAP recommends more attention be paid to physical activity and a healthy diet early in life. Pediatricians are advised to help families locate suitable opportunities for adaptive sports and recreation.
Almost 50% of children and adolescents with cerebral palsy have intellectual disability, 60%-80% have difficulty speaking, and about 25% are nonverbal. To address this, pediatricians should maximize the use of augmentative and alternative communication devices and involve experts in speech and language pathology, according to the guidelines.
“Many individuals with cerebral palsy and severe motor limitations have active, creative minds, and may need assistive technology, such as electronic talking devices, to demonstrate that mental life,” said Dr. Feldman. “Primary care clinicians should advocate for assistive technology.”
For challenging behavior, especially in the patient with limited verbal skills, potential nonbehavioral culprits such as constipation, esophageal reflux disease, and musculoskeletal or dental pain must be ruled out.
In the lead-up to adolescence, youth with cerebral palsy must be prepared for puberty, menstruation, and healthy, safe sexual relationships, much like their nonaffected peers. Since a disproportionate number of children with cerebral palsy experience neglect and physical, sexual, and emotional abuse, however, family stressors should be identified and caregivers referred for support services.
For the transition from pediatric to adult health care, the AAP recommends that structured planning begin between 12 and 14 years of age. Before transfer, the pediatrician should prepare a comprehensive medical summary with the input of the patient, parent/guardian, and pediatric subspecialists.
Without a proper handoff, “there is an increased risk of morbidity, medical complications, unnecessary emergency department visits, hospitalizations, and procedures,” the authors warned.
Transitions are likely to run more smoothly when youth are given the opportunity to understand their medical condition and be involved in decisions about their health. With this in mind, the AAP recommends that pediatricians actively discourage overprotective parents from getting in the way of their child developing “maximal independence.”
No potential conflicts of interest were disclosed by the authors, Dr. Shah, or Dr. Feldman.
*This story was updated on Nov. 28, 2022.
Updated clinical guidelines for the early diagnosis and management of cerebral palsy have been issued by the American Academy of Pediatrics.
Coauthored with the American Academy for Cerebral Palsy and Developmental Medicine, the report builds on new evidence for improved care and outcomes since the 2006 consensus guidelines.
Cerebral palsy, the most common neuromotor disorder of childhood, is often accompanied by cognitive impairments, epilepsy, sensory impairments, behavioral problems, communication difficulties, breathing and sleep problems, gastrointestinal and nutritional problems, and bone and orthopedic problems.
In the United States, the estimated prevalence of cerebral palsy ranges from 1.5 to 4 per 1,000 live births.
“Early identification and initiation of evidence-based motor therapies can improve outcomes by taking advantage of the neuroplasticity in the infant brain,” said the guideline authors in an executive summary.
The guideline, published in Pediatrics, is directed to primary care physicians with pediatrics, family practice, or internal medicine training. “It’s a much more comprehensive overview of the important role that primary care providers play in the lifetime care of people with cerebral palsy,” explained Garey Noritz, MD, chair of the 2021-2022 Executive Committee of the Council on Children with Disabilities. Dr. Noritz, a professor of pediatrics at Ohio State University and division chief of the complex health care program at Nationwide Children’s Hospital, both in Columbus, said: “The combined efforts of the primary care physician and specialty providers are needed to achieve the best outcomes.”
The AAP recommends that primary care pediatricians, neonatologists, and other specialists caring for hospitalized newborns recognize those at high risk of cerebral palsy, diagnose them as early as possible, and promptly refer them for therapy. Primary care physicians are advised to identify motor delays early by formalizing standardized developmental surveillance and screening at 9, 18, and 30 months, and to implement family-centered care across multiple specialists.
“If a motor disorder is suspected, primary care physicians should simultaneously begin a medical evaluation, refer to a specialist for definitive diagnosis, and to therapists for treatment,” Dr. Noritz emphasized.
“The earlier any possible movement disorder is recognized and intervention begins, the better a child can develop a gait pattern and work toward living an independent life, said Manish N. Shah, MD, associate professor of pediatric neurosurgery at the University of Texas, Houston, who was not involved in developing the guidelines.
For children in whom physical therapy and medication have not reduced leg spasticity, a minimally invasive spinal procedure can help release contracted tendons and encourage independent walking. The optimal age for selective dorsal rhizotomy is about 4 years, said Dr. Shah, who is director of the Texas Comprehensive Spasticity Center at Children’s Memorial Hermann Hospital in Houston. “You can turn these children into walkers. As adults, they can get jobs, have their own families. It’s life-changing.”
Importantly, the guidelines address the health care disparities leading to a higher prevalence of cerebral palsy in Black children and in those from families with lower socioeconomic status. “Efforts to combat racism and eliminate barriers to culturally sensitive prenatal, perinatal, and later pediatric care may help to improve outcomes for all children with cerebral palsy,” the authors said.
“Every child with cerebral palsy needs an individual plan, but only 30% or 40% are getting interventions,” said Dr. Shah. The updated guidelines could help payers rethink the 15-20 visits a year that are often approved, compared with the 2-3 visits per week that are needed for speech, physical, and occupational therapy, he pointed out.
“Financial issues often compromise the interdisciplinary and coordinated care associated with favorable outcomes in children with cerebral palsy,” said Heidi Feldman, MD, PhD, a developmental and behavioral pediatric specialist at Stanford (Calif.) Medicine Children’s Health’s Johnson Center for Pregnancy and Newborn Services. “With a new guideline, there may be greater willingness to fund these essential services.”
In the meantime, the AAP recommends that pediatricians advise families about available medical, social, and educational services, such as early intervention services, the Title V Maternal and Child Health block grant program, and special education services through the public school system.
Children with cerebral palsy need the same standardized primary care as any child, including the full schedule of recommended vaccinations and vision and hearing testing. They also need to be monitored and treated for the many problems that commonly co-occur, including chronic pain.
When secondary complications arise, the frequency of visits should increase.
Pneumonia, the leading cause of death in children and adolescents with cerebral palsy, can be prevented or minimized through immunization against respiratory diseases and screening for signs and symptoms of aspiration and sleep-disordered breathing.
The AAP also recommends that symptoms or functional declines undergo full investigation into other potential causes.
Since the sedentary lifestyle associated with cerebral palsy is now known to be related to the higher rates of cardiovascular complications in this patient population, the AAP recommends more attention be paid to physical activity and a healthy diet early in life. Pediatricians are advised to help families locate suitable opportunities for adaptive sports and recreation.
Almost 50% of children and adolescents with cerebral palsy have intellectual disability, 60%-80% have difficulty speaking, and about 25% are nonverbal. To address this, pediatricians should maximize the use of augmentative and alternative communication devices and involve experts in speech and language pathology, according to the guidelines.
“Many individuals with cerebral palsy and severe motor limitations have active, creative minds, and may need assistive technology, such as electronic talking devices, to demonstrate that mental life,” said Dr. Feldman. “Primary care clinicians should advocate for assistive technology.”
For challenging behavior, especially in the patient with limited verbal skills, potential nonbehavioral culprits such as constipation, esophageal reflux disease, and musculoskeletal or dental pain must be ruled out.
In the lead-up to adolescence, youth with cerebral palsy must be prepared for puberty, menstruation, and healthy, safe sexual relationships, much like their nonaffected peers. Since a disproportionate number of children with cerebral palsy experience neglect and physical, sexual, and emotional abuse, however, family stressors should be identified and caregivers referred for support services.
For the transition from pediatric to adult health care, the AAP recommends that structured planning begin between 12 and 14 years of age. Before transfer, the pediatrician should prepare a comprehensive medical summary with the input of the patient, parent/guardian, and pediatric subspecialists.
Without a proper handoff, “there is an increased risk of morbidity, medical complications, unnecessary emergency department visits, hospitalizations, and procedures,” the authors warned.
Transitions are likely to run more smoothly when youth are given the opportunity to understand their medical condition and be involved in decisions about their health. With this in mind, the AAP recommends that pediatricians actively discourage overprotective parents from getting in the way of their child developing “maximal independence.”
No potential conflicts of interest were disclosed by the authors, Dr. Shah, or Dr. Feldman.
*This story was updated on Nov. 28, 2022.
FROM PEDIATRICS
Children with autism show distinct brain features related to motor impairment
Previous research suggests that individuals with ASD overlap in motor impairment with those with DCD. But these two conditions may differ significantly in some areas, as children with ASD tend to show weaker skills in social motor tasks such as imitation, wrote Emil Kilroy, PhD, of the University of Southern California, Los Angeles, and colleagues.
The neurobiological basis of autism remains unknown, despite many research efforts, in part because of the heterogeneity of the disease, said corresponding author Lisa Aziz-Zadeh, PhD, also of the University of Southern California, in an interview.
Comorbidity with other disorders is a strong contributing factor to heterogeneity, and approximately 80% of autistic individuals have motor impairments and meet criteria for a diagnosis of DCD, said Dr. Aziz-Zadeh. “Controlling for other comorbidities, such as developmental coordination disorder, when trying to understand the neural basis of autism is important, so that we can understand which neural circuits are related to [core symptoms of autism] and which ones are related to motor impairments that are comorbid with autism, but not necessarily part of the core symptomology,” she explained. “We focused on white matter pathways here because many researchers now think the underlying basis of autism, besides genetics, is brain connectivity differences.”
In their study published in Scientific Reports, the researchers reviewed data from whole-brain correlational tractography for 22 individuals with autism spectrum disorder, 16 with developmental coordination disorder, and 21 normally developing individuals, who served as the control group. The mean age of the participants was approximately 11 years; the age range was 8-17 years.
Overall, patterns of brain diffusion (movement of fluid, mainly water molecules, in the brain) were significantly different in ASD children, compared with typically developing children.
The ASD group showed significantly reduced diffusivity in the bilateral fronto-parietal cingulum and the left parolfactory cingulum. This finding reflects previous studies suggesting an association between brain patterns in the cingulum area and ASD. But the current study is “the first to identify the fronto-parietal and the parolfactory portions of the cingulum as well as the anterior caudal u-fibers as specific to core ASD symptomatology and not related to motor-related comorbidity,” the researchers wrote.
Differences in brain diffusivity were associated with worse performance on motor skills and behavioral measures for children with ASD and children with DCD, compared with controls.
Motor development was assessed using the Total Movement Assessment Battery for Children-2 (MABC-2) and the Florida Apraxia Battery modified for children (FAB-M). The MABC-2 is among the most common tools for measuring motor skills and identifying clinically relevant motor deficits in children and teens aged 3-16 years. The test includes three subtest scores (manual dexterity, gross-motor aiming and catching, and balance) and a total score. Scores are based on a child’s best performance on each component, and higher scores indicate better functioning. In the new study, The MABC-2 total scores averaged 10.57 for controls, compared with 5.76 in the ASD group, and 4.31 in the DCD group.
Children with ASD differed from the other groups in social measures. Social skills were measured using several tools, including the Social Responsivity Scale (SRS Total), which is a parent-completed survey that includes a total score designed to reflect the severity of social deficits in ASD. It is divided into five subscales for parents to assess a child’s social skill impairment: social awareness, social cognition, social communication, social motivation, and mannerisms. Scores for the SRS are calculated in T-scores, in which a score of 50 represents the mean. T-scores of 59 and below are generally not associated with ASD, and patients with these scores are considered to have low to no symptomatology. Scores on the SRS Total in the new study were 45.95, 77.45, and 55.81 for the controls, ASD group, and DCD group, respectively.
Results should raise awareness
“The results were largely predicted in our hypotheses – that we would find specific white matter pathways in autism that would differ from [what we saw in typically developing patients and those with DCD], and that diffusivity in ASD would be related to socioemotional differences,” Dr. Aziz-Zadeh said, in an interview.
“What was surprising was that some pathways that had previously been thought to be different in autism were also compromised in DCD, indicating that they were common to motor deficits which both groups shared, not to core autism symptomology,” she noted.
A message for clinicians from the study is that a dual diagnosis of DCD is often missing in ASD practice, said Dr. Aziz-Zadeh. “Given that approximately 80% of children with ASD have DCD, testing for DCD and addressing potential motor issues should be more common practice,” she said.
Dr. Aziz-Zadeh and colleagues are now investigating relationships between the brain, behavior, and the gut microbiome. “We think that understanding autism from a full-body perspective, examining interactions between the brain and the body, will be an important step in this field,” she emphasized.
The study was limited by several factors, including the small sample size, the use of only right-handed participants, and the use of self-reports by children and parents, the researchers noted. Additionally, they noted that white matter develops at different rates in different age groups, and future studies might consider age as a factor, as well as further behavioral assessments, they said.
Small sample size limits conclusions
“Understanding the neuroanatomic differences that may contribute to the core symptoms of ASD is a very important goal for the field, particularly how they relate to other comorbid symptoms and neurodevelopmental disorders,” said Michael Gandal, MD, of the department of psychiatry at the University of Pennsylvania, Philadelphia, and a member of the Lifespan Brain Institute at the Children’s Hospital of Philadelphia, in an interview.
“While this study provides some clues into how structural connectivity may relate to motor coordination in ASD, it will be important to replicate these findings in a much larger sample before we can really appreciate how robust these findings are and how well they generalize to the broader ASD population,” Dr. Gandal emphasized.
The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Gandal had no financial conflicts to disclose.
Previous research suggests that individuals with ASD overlap in motor impairment with those with DCD. But these two conditions may differ significantly in some areas, as children with ASD tend to show weaker skills in social motor tasks such as imitation, wrote Emil Kilroy, PhD, of the University of Southern California, Los Angeles, and colleagues.
The neurobiological basis of autism remains unknown, despite many research efforts, in part because of the heterogeneity of the disease, said corresponding author Lisa Aziz-Zadeh, PhD, also of the University of Southern California, in an interview.
Comorbidity with other disorders is a strong contributing factor to heterogeneity, and approximately 80% of autistic individuals have motor impairments and meet criteria for a diagnosis of DCD, said Dr. Aziz-Zadeh. “Controlling for other comorbidities, such as developmental coordination disorder, when trying to understand the neural basis of autism is important, so that we can understand which neural circuits are related to [core symptoms of autism] and which ones are related to motor impairments that are comorbid with autism, but not necessarily part of the core symptomology,” she explained. “We focused on white matter pathways here because many researchers now think the underlying basis of autism, besides genetics, is brain connectivity differences.”
In their study published in Scientific Reports, the researchers reviewed data from whole-brain correlational tractography for 22 individuals with autism spectrum disorder, 16 with developmental coordination disorder, and 21 normally developing individuals, who served as the control group. The mean age of the participants was approximately 11 years; the age range was 8-17 years.
Overall, patterns of brain diffusion (movement of fluid, mainly water molecules, in the brain) were significantly different in ASD children, compared with typically developing children.
The ASD group showed significantly reduced diffusivity in the bilateral fronto-parietal cingulum and the left parolfactory cingulum. This finding reflects previous studies suggesting an association between brain patterns in the cingulum area and ASD. But the current study is “the first to identify the fronto-parietal and the parolfactory portions of the cingulum as well as the anterior caudal u-fibers as specific to core ASD symptomatology and not related to motor-related comorbidity,” the researchers wrote.
Differences in brain diffusivity were associated with worse performance on motor skills and behavioral measures for children with ASD and children with DCD, compared with controls.
Motor development was assessed using the Total Movement Assessment Battery for Children-2 (MABC-2) and the Florida Apraxia Battery modified for children (FAB-M). The MABC-2 is among the most common tools for measuring motor skills and identifying clinically relevant motor deficits in children and teens aged 3-16 years. The test includes three subtest scores (manual dexterity, gross-motor aiming and catching, and balance) and a total score. Scores are based on a child’s best performance on each component, and higher scores indicate better functioning. In the new study, The MABC-2 total scores averaged 10.57 for controls, compared with 5.76 in the ASD group, and 4.31 in the DCD group.
Children with ASD differed from the other groups in social measures. Social skills were measured using several tools, including the Social Responsivity Scale (SRS Total), which is a parent-completed survey that includes a total score designed to reflect the severity of social deficits in ASD. It is divided into five subscales for parents to assess a child’s social skill impairment: social awareness, social cognition, social communication, social motivation, and mannerisms. Scores for the SRS are calculated in T-scores, in which a score of 50 represents the mean. T-scores of 59 and below are generally not associated with ASD, and patients with these scores are considered to have low to no symptomatology. Scores on the SRS Total in the new study were 45.95, 77.45, and 55.81 for the controls, ASD group, and DCD group, respectively.
Results should raise awareness
“The results were largely predicted in our hypotheses – that we would find specific white matter pathways in autism that would differ from [what we saw in typically developing patients and those with DCD], and that diffusivity in ASD would be related to socioemotional differences,” Dr. Aziz-Zadeh said, in an interview.
“What was surprising was that some pathways that had previously been thought to be different in autism were also compromised in DCD, indicating that they were common to motor deficits which both groups shared, not to core autism symptomology,” she noted.
A message for clinicians from the study is that a dual diagnosis of DCD is often missing in ASD practice, said Dr. Aziz-Zadeh. “Given that approximately 80% of children with ASD have DCD, testing for DCD and addressing potential motor issues should be more common practice,” she said.
Dr. Aziz-Zadeh and colleagues are now investigating relationships between the brain, behavior, and the gut microbiome. “We think that understanding autism from a full-body perspective, examining interactions between the brain and the body, will be an important step in this field,” she emphasized.
The study was limited by several factors, including the small sample size, the use of only right-handed participants, and the use of self-reports by children and parents, the researchers noted. Additionally, they noted that white matter develops at different rates in different age groups, and future studies might consider age as a factor, as well as further behavioral assessments, they said.
Small sample size limits conclusions
“Understanding the neuroanatomic differences that may contribute to the core symptoms of ASD is a very important goal for the field, particularly how they relate to other comorbid symptoms and neurodevelopmental disorders,” said Michael Gandal, MD, of the department of psychiatry at the University of Pennsylvania, Philadelphia, and a member of the Lifespan Brain Institute at the Children’s Hospital of Philadelphia, in an interview.
“While this study provides some clues into how structural connectivity may relate to motor coordination in ASD, it will be important to replicate these findings in a much larger sample before we can really appreciate how robust these findings are and how well they generalize to the broader ASD population,” Dr. Gandal emphasized.
The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Gandal had no financial conflicts to disclose.
Previous research suggests that individuals with ASD overlap in motor impairment with those with DCD. But these two conditions may differ significantly in some areas, as children with ASD tend to show weaker skills in social motor tasks such as imitation, wrote Emil Kilroy, PhD, of the University of Southern California, Los Angeles, and colleagues.
The neurobiological basis of autism remains unknown, despite many research efforts, in part because of the heterogeneity of the disease, said corresponding author Lisa Aziz-Zadeh, PhD, also of the University of Southern California, in an interview.
Comorbidity with other disorders is a strong contributing factor to heterogeneity, and approximately 80% of autistic individuals have motor impairments and meet criteria for a diagnosis of DCD, said Dr. Aziz-Zadeh. “Controlling for other comorbidities, such as developmental coordination disorder, when trying to understand the neural basis of autism is important, so that we can understand which neural circuits are related to [core symptoms of autism] and which ones are related to motor impairments that are comorbid with autism, but not necessarily part of the core symptomology,” she explained. “We focused on white matter pathways here because many researchers now think the underlying basis of autism, besides genetics, is brain connectivity differences.”
In their study published in Scientific Reports, the researchers reviewed data from whole-brain correlational tractography for 22 individuals with autism spectrum disorder, 16 with developmental coordination disorder, and 21 normally developing individuals, who served as the control group. The mean age of the participants was approximately 11 years; the age range was 8-17 years.
Overall, patterns of brain diffusion (movement of fluid, mainly water molecules, in the brain) were significantly different in ASD children, compared with typically developing children.
The ASD group showed significantly reduced diffusivity in the bilateral fronto-parietal cingulum and the left parolfactory cingulum. This finding reflects previous studies suggesting an association between brain patterns in the cingulum area and ASD. But the current study is “the first to identify the fronto-parietal and the parolfactory portions of the cingulum as well as the anterior caudal u-fibers as specific to core ASD symptomatology and not related to motor-related comorbidity,” the researchers wrote.
Differences in brain diffusivity were associated with worse performance on motor skills and behavioral measures for children with ASD and children with DCD, compared with controls.
Motor development was assessed using the Total Movement Assessment Battery for Children-2 (MABC-2) and the Florida Apraxia Battery modified for children (FAB-M). The MABC-2 is among the most common tools for measuring motor skills and identifying clinically relevant motor deficits in children and teens aged 3-16 years. The test includes three subtest scores (manual dexterity, gross-motor aiming and catching, and balance) and a total score. Scores are based on a child’s best performance on each component, and higher scores indicate better functioning. In the new study, The MABC-2 total scores averaged 10.57 for controls, compared with 5.76 in the ASD group, and 4.31 in the DCD group.
Children with ASD differed from the other groups in social measures. Social skills were measured using several tools, including the Social Responsivity Scale (SRS Total), which is a parent-completed survey that includes a total score designed to reflect the severity of social deficits in ASD. It is divided into five subscales for parents to assess a child’s social skill impairment: social awareness, social cognition, social communication, social motivation, and mannerisms. Scores for the SRS are calculated in T-scores, in which a score of 50 represents the mean. T-scores of 59 and below are generally not associated with ASD, and patients with these scores are considered to have low to no symptomatology. Scores on the SRS Total in the new study were 45.95, 77.45, and 55.81 for the controls, ASD group, and DCD group, respectively.
Results should raise awareness
“The results were largely predicted in our hypotheses – that we would find specific white matter pathways in autism that would differ from [what we saw in typically developing patients and those with DCD], and that diffusivity in ASD would be related to socioemotional differences,” Dr. Aziz-Zadeh said, in an interview.
“What was surprising was that some pathways that had previously been thought to be different in autism were also compromised in DCD, indicating that they were common to motor deficits which both groups shared, not to core autism symptomology,” she noted.
A message for clinicians from the study is that a dual diagnosis of DCD is often missing in ASD practice, said Dr. Aziz-Zadeh. “Given that approximately 80% of children with ASD have DCD, testing for DCD and addressing potential motor issues should be more common practice,” she said.
Dr. Aziz-Zadeh and colleagues are now investigating relationships between the brain, behavior, and the gut microbiome. “We think that understanding autism from a full-body perspective, examining interactions between the brain and the body, will be an important step in this field,” she emphasized.
The study was limited by several factors, including the small sample size, the use of only right-handed participants, and the use of self-reports by children and parents, the researchers noted. Additionally, they noted that white matter develops at different rates in different age groups, and future studies might consider age as a factor, as well as further behavioral assessments, they said.
Small sample size limits conclusions
“Understanding the neuroanatomic differences that may contribute to the core symptoms of ASD is a very important goal for the field, particularly how they relate to other comorbid symptoms and neurodevelopmental disorders,” said Michael Gandal, MD, of the department of psychiatry at the University of Pennsylvania, Philadelphia, and a member of the Lifespan Brain Institute at the Children’s Hospital of Philadelphia, in an interview.
“While this study provides some clues into how structural connectivity may relate to motor coordination in ASD, it will be important to replicate these findings in a much larger sample before we can really appreciate how robust these findings are and how well they generalize to the broader ASD population,” Dr. Gandal emphasized.
The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Gandal had no financial conflicts to disclose.
FROM SCIENTIFIC REPORTS