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Biomarkers support impact of concussions on cognitive function
Former athletes with a history of concussion averaged higher levels of total tau in their cerebrospinal fluid than did healthy controls, and those with the highest levels showed signs of reduced cognitive function in a case-control study.
Chronic traumatic encephalopathy (CTE) remains a postmortem diagnosis, but “the potential for treating postconcussion degeneration such as CTE depends on being able to detect the in vivo pathology at an early stage to intervene before the disease progresses to an irreversible stage,” wrote Foad Taghdiri, MD, of the University of Toronto and colleagues.
In a study published in Neurology, the researchers measured concentrations of phosphorylated tau181, total tau (t-tau), and beta-amyloid in the cerebrospinal fluid (CSF) of three groups: 22 former professional athletes who had suffered multiple concussions, 5 healthy controls, and 12 individuals diagnosed with Alzheimer’s disease (AD). The average ages of the groups were 56 years, 57 years, and 60 years, respectively. All the athletes were male, and their sports included snowboarding, hockey, and football.
The average t-tau level in the CSF of the athletes was significantly higher than that of controls (349.3 pg/mL vs. 188.8 pg/mL) and significantly lower than that of AD patients (857.0 pg/mL).
Normal CSF t-tau was defined as 300 pg/mL, and 12 former athletes (45%) had high t-tau levels, with an average of 499.3 pg/mL. In this group of high t-tau former athletes, the average score on the Trail Making Test (TMT) Part B was significantly lower than the average score among the 10 former athletes with normal CSF t-tau levels (t scores 45.6 vs. 62.3; P = .017).
In addition, results from MRI scans showed that fractional anisotropy values across all the tracts were significantly lower for those with high CSF t-tau levels, compared with those who had normal CSF t-tau levels (P = .036).
The findings were limited by several factors, including the small sample size, lack of female athletes, and limited ability to compare white matter integrity between high and normal CSF t-tau groups, the researchers noted.
However, the results suggest that “multiple concussive or subconcussive events may trigger neurodegeneration to a greater degree than expected on the basis of age alone,” they said. Although the study did not allow for diagnosing the participants with CTE, “we are engaged in longitudinal studies to track neurologic and neuropsychological function, CSF biomarkers, and structural brain changes over time to further assess the delayed effects of multiple concussions on the brain,” the researchers wrote.
The study was funded by the Toronto General and Western Hospital Foundation, PSI Foundation, and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose.
SOURCE: Taghdiri F et al. Neurology. 2019 May 8. doi: 10.1212/WNL.0000000000007608
Former athletes with a history of concussion averaged higher levels of total tau in their cerebrospinal fluid than did healthy controls, and those with the highest levels showed signs of reduced cognitive function in a case-control study.
Chronic traumatic encephalopathy (CTE) remains a postmortem diagnosis, but “the potential for treating postconcussion degeneration such as CTE depends on being able to detect the in vivo pathology at an early stage to intervene before the disease progresses to an irreversible stage,” wrote Foad Taghdiri, MD, of the University of Toronto and colleagues.
In a study published in Neurology, the researchers measured concentrations of phosphorylated tau181, total tau (t-tau), and beta-amyloid in the cerebrospinal fluid (CSF) of three groups: 22 former professional athletes who had suffered multiple concussions, 5 healthy controls, and 12 individuals diagnosed with Alzheimer’s disease (AD). The average ages of the groups were 56 years, 57 years, and 60 years, respectively. All the athletes were male, and their sports included snowboarding, hockey, and football.
The average t-tau level in the CSF of the athletes was significantly higher than that of controls (349.3 pg/mL vs. 188.8 pg/mL) and significantly lower than that of AD patients (857.0 pg/mL).
Normal CSF t-tau was defined as 300 pg/mL, and 12 former athletes (45%) had high t-tau levels, with an average of 499.3 pg/mL. In this group of high t-tau former athletes, the average score on the Trail Making Test (TMT) Part B was significantly lower than the average score among the 10 former athletes with normal CSF t-tau levels (t scores 45.6 vs. 62.3; P = .017).
In addition, results from MRI scans showed that fractional anisotropy values across all the tracts were significantly lower for those with high CSF t-tau levels, compared with those who had normal CSF t-tau levels (P = .036).
The findings were limited by several factors, including the small sample size, lack of female athletes, and limited ability to compare white matter integrity between high and normal CSF t-tau groups, the researchers noted.
However, the results suggest that “multiple concussive or subconcussive events may trigger neurodegeneration to a greater degree than expected on the basis of age alone,” they said. Although the study did not allow for diagnosing the participants with CTE, “we are engaged in longitudinal studies to track neurologic and neuropsychological function, CSF biomarkers, and structural brain changes over time to further assess the delayed effects of multiple concussions on the brain,” the researchers wrote.
The study was funded by the Toronto General and Western Hospital Foundation, PSI Foundation, and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose.
SOURCE: Taghdiri F et al. Neurology. 2019 May 8. doi: 10.1212/WNL.0000000000007608
Former athletes with a history of concussion averaged higher levels of total tau in their cerebrospinal fluid than did healthy controls, and those with the highest levels showed signs of reduced cognitive function in a case-control study.
Chronic traumatic encephalopathy (CTE) remains a postmortem diagnosis, but “the potential for treating postconcussion degeneration such as CTE depends on being able to detect the in vivo pathology at an early stage to intervene before the disease progresses to an irreversible stage,” wrote Foad Taghdiri, MD, of the University of Toronto and colleagues.
In a study published in Neurology, the researchers measured concentrations of phosphorylated tau181, total tau (t-tau), and beta-amyloid in the cerebrospinal fluid (CSF) of three groups: 22 former professional athletes who had suffered multiple concussions, 5 healthy controls, and 12 individuals diagnosed with Alzheimer’s disease (AD). The average ages of the groups were 56 years, 57 years, and 60 years, respectively. All the athletes were male, and their sports included snowboarding, hockey, and football.
The average t-tau level in the CSF of the athletes was significantly higher than that of controls (349.3 pg/mL vs. 188.8 pg/mL) and significantly lower than that of AD patients (857.0 pg/mL).
Normal CSF t-tau was defined as 300 pg/mL, and 12 former athletes (45%) had high t-tau levels, with an average of 499.3 pg/mL. In this group of high t-tau former athletes, the average score on the Trail Making Test (TMT) Part B was significantly lower than the average score among the 10 former athletes with normal CSF t-tau levels (t scores 45.6 vs. 62.3; P = .017).
In addition, results from MRI scans showed that fractional anisotropy values across all the tracts were significantly lower for those with high CSF t-tau levels, compared with those who had normal CSF t-tau levels (P = .036).
The findings were limited by several factors, including the small sample size, lack of female athletes, and limited ability to compare white matter integrity between high and normal CSF t-tau groups, the researchers noted.
However, the results suggest that “multiple concussive or subconcussive events may trigger neurodegeneration to a greater degree than expected on the basis of age alone,” they said. Although the study did not allow for diagnosing the participants with CTE, “we are engaged in longitudinal studies to track neurologic and neuropsychological function, CSF biomarkers, and structural brain changes over time to further assess the delayed effects of multiple concussions on the brain,” the researchers wrote.
The study was funded by the Toronto General and Western Hospital Foundation, PSI Foundation, and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose.
SOURCE: Taghdiri F et al. Neurology. 2019 May 8. doi: 10.1212/WNL.0000000000007608
FROM NEUROLOGY
Insomnia meds get boxed warning from FDA
The Food and Drug Administration will now require that certain
Complex sleep behaviors have been seen with these medications in patients with and without a history of them, at low doses, and even after one dose of the medication. They’ve also been observed with and without concomitant use of alcohol or other CNS depressants.
Health care professionals should advise patients about these risks, even though they are rare. Patients should contact health care professionals if they either experience a complex sleep behavior while not fully awake on one of these medicines or have performed activities they don’t remember while taking the medicine.
More information about these risks and the safety warnings can be found in the FDA’s safety announcement. Other information is also available in a press announcement from the agency.
The Food and Drug Administration will now require that certain
Complex sleep behaviors have been seen with these medications in patients with and without a history of them, at low doses, and even after one dose of the medication. They’ve also been observed with and without concomitant use of alcohol or other CNS depressants.
Health care professionals should advise patients about these risks, even though they are rare. Patients should contact health care professionals if they either experience a complex sleep behavior while not fully awake on one of these medicines or have performed activities they don’t remember while taking the medicine.
More information about these risks and the safety warnings can be found in the FDA’s safety announcement. Other information is also available in a press announcement from the agency.
The Food and Drug Administration will now require that certain
Complex sleep behaviors have been seen with these medications in patients with and without a history of them, at low doses, and even after one dose of the medication. They’ve also been observed with and without concomitant use of alcohol or other CNS depressants.
Health care professionals should advise patients about these risks, even though they are rare. Patients should contact health care professionals if they either experience a complex sleep behavior while not fully awake on one of these medicines or have performed activities they don’t remember while taking the medicine.
More information about these risks and the safety warnings can be found in the FDA’s safety announcement. Other information is also available in a press announcement from the agency.
Racial, economic disparities found in buprenorphine prescriptions
Buprenorphine for opioid use disorder is much less likely to be prescribed to patients who are black or who do not have health insurance, an analysis of two national surveys shows.
Researchers analyzed data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 2004 to 2015, including 13.4 million visits in which buprenorphine was prescribed. The analysis was published as a research letter in JAMA Psychiatry.
From 2012 to 2015, the number of ambulatory visits involving buprenorphine rose from 0.04% to 0.36%. Black patients were 77% less likely to receive a prescription for buprenorphine at their visit – even after adjustment for payment method, sex, and age – while the number of prescription received by white patients was considerably higher than for patients of any other ethnicity, wrote Pooja A. Lagisetty, MD, and coauthors.
, and the age group with the highest incidence of buprenorphine prescriptions was 30-50 years.
Self-pay and private health insurance were the most common payment methods, but the number of self-paying patients receiving buprenorphine prescriptions dramatically increased from 585,568 in 2004-2007 to 5.3 million in 2012-2015.
“This finding in nationally representative data builds on a previous study that reported buprenorphine treatment disparities on the basis of race/ethnicity and income in New York City,” said Dr. Lagisetty of the department of medicine at the University of Michigan, Ann Arbor, and coauthors.
However, they acknowledged that it was unclear whether the treatment disparity might in fact reflect a difference in the prevalence of opioid use disorder across ethnicities.
Commenting on the differences in payment methods, the authors noted that, despite the enactment of mental health parity legislation and the expansion of Medicaid, the proportion of self-pay visits remained relatively unchanged across the study period.
“A recent study demonstrated that half of the physicians prescribing buprenorphine in Ohio accepted cash alone, and our findings suggest that this practice may be widespread and may be associated with additional financial barriers for low-income populations,” the researchers wrote. “With rising rates of opioid overdoses, it is imperative that policy and research efforts specifically address racial/ethnic and economic differences in treatment access and engagement.”
No conflicts of interest were declared.
SOURCE: Lagisetty P et al. JAMA Psychiatry. 2019 May 8. doi: 10.1001/jamapsychiatry.2019.0876.
Buprenorphine for opioid use disorder is much less likely to be prescribed to patients who are black or who do not have health insurance, an analysis of two national surveys shows.
Researchers analyzed data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 2004 to 2015, including 13.4 million visits in which buprenorphine was prescribed. The analysis was published as a research letter in JAMA Psychiatry.
From 2012 to 2015, the number of ambulatory visits involving buprenorphine rose from 0.04% to 0.36%. Black patients were 77% less likely to receive a prescription for buprenorphine at their visit – even after adjustment for payment method, sex, and age – while the number of prescription received by white patients was considerably higher than for patients of any other ethnicity, wrote Pooja A. Lagisetty, MD, and coauthors.
, and the age group with the highest incidence of buprenorphine prescriptions was 30-50 years.
Self-pay and private health insurance were the most common payment methods, but the number of self-paying patients receiving buprenorphine prescriptions dramatically increased from 585,568 in 2004-2007 to 5.3 million in 2012-2015.
“This finding in nationally representative data builds on a previous study that reported buprenorphine treatment disparities on the basis of race/ethnicity and income in New York City,” said Dr. Lagisetty of the department of medicine at the University of Michigan, Ann Arbor, and coauthors.
However, they acknowledged that it was unclear whether the treatment disparity might in fact reflect a difference in the prevalence of opioid use disorder across ethnicities.
Commenting on the differences in payment methods, the authors noted that, despite the enactment of mental health parity legislation and the expansion of Medicaid, the proportion of self-pay visits remained relatively unchanged across the study period.
“A recent study demonstrated that half of the physicians prescribing buprenorphine in Ohio accepted cash alone, and our findings suggest that this practice may be widespread and may be associated with additional financial barriers for low-income populations,” the researchers wrote. “With rising rates of opioid overdoses, it is imperative that policy and research efforts specifically address racial/ethnic and economic differences in treatment access and engagement.”
No conflicts of interest were declared.
SOURCE: Lagisetty P et al. JAMA Psychiatry. 2019 May 8. doi: 10.1001/jamapsychiatry.2019.0876.
Buprenorphine for opioid use disorder is much less likely to be prescribed to patients who are black or who do not have health insurance, an analysis of two national surveys shows.
Researchers analyzed data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 2004 to 2015, including 13.4 million visits in which buprenorphine was prescribed. The analysis was published as a research letter in JAMA Psychiatry.
From 2012 to 2015, the number of ambulatory visits involving buprenorphine rose from 0.04% to 0.36%. Black patients were 77% less likely to receive a prescription for buprenorphine at their visit – even after adjustment for payment method, sex, and age – while the number of prescription received by white patients was considerably higher than for patients of any other ethnicity, wrote Pooja A. Lagisetty, MD, and coauthors.
, and the age group with the highest incidence of buprenorphine prescriptions was 30-50 years.
Self-pay and private health insurance were the most common payment methods, but the number of self-paying patients receiving buprenorphine prescriptions dramatically increased from 585,568 in 2004-2007 to 5.3 million in 2012-2015.
“This finding in nationally representative data builds on a previous study that reported buprenorphine treatment disparities on the basis of race/ethnicity and income in New York City,” said Dr. Lagisetty of the department of medicine at the University of Michigan, Ann Arbor, and coauthors.
However, they acknowledged that it was unclear whether the treatment disparity might in fact reflect a difference in the prevalence of opioid use disorder across ethnicities.
Commenting on the differences in payment methods, the authors noted that, despite the enactment of mental health parity legislation and the expansion of Medicaid, the proportion of self-pay visits remained relatively unchanged across the study period.
“A recent study demonstrated that half of the physicians prescribing buprenorphine in Ohio accepted cash alone, and our findings suggest that this practice may be widespread and may be associated with additional financial barriers for low-income populations,” the researchers wrote. “With rising rates of opioid overdoses, it is imperative that policy and research efforts specifically address racial/ethnic and economic differences in treatment access and engagement.”
No conflicts of interest were declared.
SOURCE: Lagisetty P et al. JAMA Psychiatry. 2019 May 8. doi: 10.1001/jamapsychiatry.2019.0876.
FROM JAMA PSYCHIATRY
Ruzurgi approved for Lambert-Eaton myasthenic syndrome in patients under age 17
Amifampridine (Ruzurgi) has been approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder, in patients aged 6 to less than 17 years, according to a statement from the Food and Drug Administration.
The approval is the first for a LEMS treatment specifically for pediatric patients.
“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
The prevalence of LEMS in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide, according to the FDA press release.
Use of amifampridine in patients 6 to less than 17 years of age is supported by pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients 6 to less than 17 years of age.
A randomized, double-blind, placebo-controlled withdrawal study enrolled 32 adult patients who had taken amifampridine for at least 3 months. The study compared patients continuing on amifampridine with patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients who continued on amifampridine experienced less impairment compared with those switched to placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness. The scores indicated greater perceived weakening in the patients switched to placebo.
The most common side effects among amifampridine users were paresthesia, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Signs of hypersensitivity reactions include rash, hives, itching, fever, swelling, or trouble breathing.
The FDA granted this application Priority Review and Fast Track designations. Amifampridine also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of amifampridine (Ruzurgi) to Jacobus Pharmaceutical Company.
Amifampridine (Ruzurgi) has been approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder, in patients aged 6 to less than 17 years, according to a statement from the Food and Drug Administration.
The approval is the first for a LEMS treatment specifically for pediatric patients.
“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
The prevalence of LEMS in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide, according to the FDA press release.
Use of amifampridine in patients 6 to less than 17 years of age is supported by pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients 6 to less than 17 years of age.
A randomized, double-blind, placebo-controlled withdrawal study enrolled 32 adult patients who had taken amifampridine for at least 3 months. The study compared patients continuing on amifampridine with patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients who continued on amifampridine experienced less impairment compared with those switched to placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness. The scores indicated greater perceived weakening in the patients switched to placebo.
The most common side effects among amifampridine users were paresthesia, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Signs of hypersensitivity reactions include rash, hives, itching, fever, swelling, or trouble breathing.
The FDA granted this application Priority Review and Fast Track designations. Amifampridine also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of amifampridine (Ruzurgi) to Jacobus Pharmaceutical Company.
Amifampridine (Ruzurgi) has been approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder, in patients aged 6 to less than 17 years, according to a statement from the Food and Drug Administration.
The approval is the first for a LEMS treatment specifically for pediatric patients.
“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
The prevalence of LEMS in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide, according to the FDA press release.
Use of amifampridine in patients 6 to less than 17 years of age is supported by pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients 6 to less than 17 years of age.
A randomized, double-blind, placebo-controlled withdrawal study enrolled 32 adult patients who had taken amifampridine for at least 3 months. The study compared patients continuing on amifampridine with patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients who continued on amifampridine experienced less impairment compared with those switched to placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness. The scores indicated greater perceived weakening in the patients switched to placebo.
The most common side effects among amifampridine users were paresthesia, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Signs of hypersensitivity reactions include rash, hives, itching, fever, swelling, or trouble breathing.
The FDA granted this application Priority Review and Fast Track designations. Amifampridine also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of amifampridine (Ruzurgi) to Jacobus Pharmaceutical Company.
Patients describe significant impact of epilepsy on their lives
PHILADELPHIA – said Jacqueline French, MD, a professor at the Comprehensive Epilepsy Center at New York University.
“This underscores the need to consider these experiences, and potentially the stage of disease, when developing patient-reported outcome measures,” she said at the annual meeting of the American Academy of Neurology.
To describe the patient’s experience of living with epilepsy, including the occurrence of disease-related signs and symptoms and impact on daily life at different disease stages, Dr. French conducted qualitative, semistructured interviews with adults with focal epilepsy at the following stages: early (1 year or less since diagnosis), middle (1-5 years since diagnosis), and late (more than 5 years since diagnosis). The patients had varying seizure frequency and treatment experiences. They were asked to describe the symptoms and functional impact they had experienced related to epilepsy, and then to rate the degree to which each symptom and impact “bothered” them, using a disturbance rating scale from 0 (not at all) to 10 (extremely).
A total of 62 patients who were aged 18-60 years (mean age, 37 years; 73% female) were interviewed. In all, 19 of the patients had early-stage disease, 17 had middle-stage, and 26 had late-stage disease. Symptoms reported with the highest frequency and highest average disturbance (AD) ratings across all cohorts included twitching/tremors (80% of patients; AD, 5.3), confusion (78%; AD, 7.8), difficulty talking (75%; AD, 8.1), impaired/loss of consciousness (70%; AD, 6.8), stiffening (65%; AD, 5.4), déjà vu (62%; AD, 5.1), difficulty remembering (60%; AD, 8.5), and dizziness/light-headedness (58%; AD, 6.4).
The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (74%; AD, 7.1), limited ability to work and/or go to school (61%; AD, 6.7), limitations on leisure and social activities (58%; AD, 6.3), and memory loss (47%; AD, 8.4).
Dr French noted that, although disease experiences were similar among the cohorts, some heterogeneity across patient subgroups was observed.
Eisai sponsored the study.
PHILADELPHIA – said Jacqueline French, MD, a professor at the Comprehensive Epilepsy Center at New York University.
“This underscores the need to consider these experiences, and potentially the stage of disease, when developing patient-reported outcome measures,” she said at the annual meeting of the American Academy of Neurology.
To describe the patient’s experience of living with epilepsy, including the occurrence of disease-related signs and symptoms and impact on daily life at different disease stages, Dr. French conducted qualitative, semistructured interviews with adults with focal epilepsy at the following stages: early (1 year or less since diagnosis), middle (1-5 years since diagnosis), and late (more than 5 years since diagnosis). The patients had varying seizure frequency and treatment experiences. They were asked to describe the symptoms and functional impact they had experienced related to epilepsy, and then to rate the degree to which each symptom and impact “bothered” them, using a disturbance rating scale from 0 (not at all) to 10 (extremely).
A total of 62 patients who were aged 18-60 years (mean age, 37 years; 73% female) were interviewed. In all, 19 of the patients had early-stage disease, 17 had middle-stage, and 26 had late-stage disease. Symptoms reported with the highest frequency and highest average disturbance (AD) ratings across all cohorts included twitching/tremors (80% of patients; AD, 5.3), confusion (78%; AD, 7.8), difficulty talking (75%; AD, 8.1), impaired/loss of consciousness (70%; AD, 6.8), stiffening (65%; AD, 5.4), déjà vu (62%; AD, 5.1), difficulty remembering (60%; AD, 8.5), and dizziness/light-headedness (58%; AD, 6.4).
The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (74%; AD, 7.1), limited ability to work and/or go to school (61%; AD, 6.7), limitations on leisure and social activities (58%; AD, 6.3), and memory loss (47%; AD, 8.4).
Dr French noted that, although disease experiences were similar among the cohorts, some heterogeneity across patient subgroups was observed.
Eisai sponsored the study.
PHILADELPHIA – said Jacqueline French, MD, a professor at the Comprehensive Epilepsy Center at New York University.
“This underscores the need to consider these experiences, and potentially the stage of disease, when developing patient-reported outcome measures,” she said at the annual meeting of the American Academy of Neurology.
To describe the patient’s experience of living with epilepsy, including the occurrence of disease-related signs and symptoms and impact on daily life at different disease stages, Dr. French conducted qualitative, semistructured interviews with adults with focal epilepsy at the following stages: early (1 year or less since diagnosis), middle (1-5 years since diagnosis), and late (more than 5 years since diagnosis). The patients had varying seizure frequency and treatment experiences. They were asked to describe the symptoms and functional impact they had experienced related to epilepsy, and then to rate the degree to which each symptom and impact “bothered” them, using a disturbance rating scale from 0 (not at all) to 10 (extremely).
A total of 62 patients who were aged 18-60 years (mean age, 37 years; 73% female) were interviewed. In all, 19 of the patients had early-stage disease, 17 had middle-stage, and 26 had late-stage disease. Symptoms reported with the highest frequency and highest average disturbance (AD) ratings across all cohorts included twitching/tremors (80% of patients; AD, 5.3), confusion (78%; AD, 7.8), difficulty talking (75%; AD, 8.1), impaired/loss of consciousness (70%; AD, 6.8), stiffening (65%; AD, 5.4), déjà vu (62%; AD, 5.1), difficulty remembering (60%; AD, 8.5), and dizziness/light-headedness (58%; AD, 6.4).
The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (74%; AD, 7.1), limited ability to work and/or go to school (61%; AD, 6.7), limitations on leisure and social activities (58%; AD, 6.3), and memory loss (47%; AD, 8.4).
Dr French noted that, although disease experiences were similar among the cohorts, some heterogeneity across patient subgroups was observed.
Eisai sponsored the study.
REPORTING FROM AAN 2019
Key clinical point: Adults with focal epilepsy report a range of high-disturbance symptoms and impacts on daily life.
Major finding: The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (reported by 74% of respondents), limited ability to work and/or go to school (61%), limitations on leisure and social activities (58%), and memory loss (47%).
Study details: Qualitative, semistructured interviews with 62 adults with focal epilepsy at different stages of illness: early, middle, and late.
Disclosures: Eisai sponsored the study.
Physical activity slows cognitive decline in patients with Parkinson’s disease
PHILADELPHIA – according to Sneha Mantri, MD, of Duke University in Durham, N.C., and colleagues, who presented the results of their study at the annual meeting of the American Academy of Neurology.
Physical activity is an important component of the management of Parkinson’s disease and is shown to mitigate cognitive decline among patients with moderate disease, said Dr. Mantri and colleagues. “Exercise levels in de novo and early disease may influence risk of future cognitive decline; early disease also presents an opportunity for early intervention and possible disease modification,” Dr. Mantri said.
Physical activity levels in early disease are known to be low, but the effects of activity on cognition are currently unclear. To assess the relationship between physical activity and cognition, Dr. Mantri and colleagues examined patients with Parkinson’s disease who were enrolled in the prospective Parkinson’s Progression Markers Initiative (PPMI) cohort. At annual study visits, participants completed the Physical Activity Scale for the Elderly (PASE), a validated self-reported questionnaire assessing household, leisure, and work activities over the previous 7 days. The researchers used a linear mixed-effects model to compare rates of change in the Montreal Cognitive Assessment (MoCA) according to PASE scores; covariates included age, sex, Unified Parkinson’s Disease Rating Scale (UPDRS) part III score, and baseline MoCA.
A total of 379 patients completed at least one PASE questionnaire over the course of the study. PASE scores in this cohort have been previously described (Mantri S et al. J Park Dis. 2018;8[1]:107-11). Although overall rates of cognitive decline are known to be modest in this early cohort, PASE over time has a significant effect on MoCA during follow-up (P = 0.02) which suggest that higher levels of activity throughout disease are associated with better cognitive performance.
Dr. Mantri had nothing to disclose. Among her coauthors, Dr. Tropea received personal compensation from Genzyme and Medtronics and research support from Sanofi. Dr. Morley had nothing to disclose.
SOURCE: Mantri S et al. AAN 2019, Abstract P2.8-021.
PHILADELPHIA – according to Sneha Mantri, MD, of Duke University in Durham, N.C., and colleagues, who presented the results of their study at the annual meeting of the American Academy of Neurology.
Physical activity is an important component of the management of Parkinson’s disease and is shown to mitigate cognitive decline among patients with moderate disease, said Dr. Mantri and colleagues. “Exercise levels in de novo and early disease may influence risk of future cognitive decline; early disease also presents an opportunity for early intervention and possible disease modification,” Dr. Mantri said.
Physical activity levels in early disease are known to be low, but the effects of activity on cognition are currently unclear. To assess the relationship between physical activity and cognition, Dr. Mantri and colleagues examined patients with Parkinson’s disease who were enrolled in the prospective Parkinson’s Progression Markers Initiative (PPMI) cohort. At annual study visits, participants completed the Physical Activity Scale for the Elderly (PASE), a validated self-reported questionnaire assessing household, leisure, and work activities over the previous 7 days. The researchers used a linear mixed-effects model to compare rates of change in the Montreal Cognitive Assessment (MoCA) according to PASE scores; covariates included age, sex, Unified Parkinson’s Disease Rating Scale (UPDRS) part III score, and baseline MoCA.
A total of 379 patients completed at least one PASE questionnaire over the course of the study. PASE scores in this cohort have been previously described (Mantri S et al. J Park Dis. 2018;8[1]:107-11). Although overall rates of cognitive decline are known to be modest in this early cohort, PASE over time has a significant effect on MoCA during follow-up (P = 0.02) which suggest that higher levels of activity throughout disease are associated with better cognitive performance.
Dr. Mantri had nothing to disclose. Among her coauthors, Dr. Tropea received personal compensation from Genzyme and Medtronics and research support from Sanofi. Dr. Morley had nothing to disclose.
SOURCE: Mantri S et al. AAN 2019, Abstract P2.8-021.
PHILADELPHIA – according to Sneha Mantri, MD, of Duke University in Durham, N.C., and colleagues, who presented the results of their study at the annual meeting of the American Academy of Neurology.
Physical activity is an important component of the management of Parkinson’s disease and is shown to mitigate cognitive decline among patients with moderate disease, said Dr. Mantri and colleagues. “Exercise levels in de novo and early disease may influence risk of future cognitive decline; early disease also presents an opportunity for early intervention and possible disease modification,” Dr. Mantri said.
Physical activity levels in early disease are known to be low, but the effects of activity on cognition are currently unclear. To assess the relationship between physical activity and cognition, Dr. Mantri and colleagues examined patients with Parkinson’s disease who were enrolled in the prospective Parkinson’s Progression Markers Initiative (PPMI) cohort. At annual study visits, participants completed the Physical Activity Scale for the Elderly (PASE), a validated self-reported questionnaire assessing household, leisure, and work activities over the previous 7 days. The researchers used a linear mixed-effects model to compare rates of change in the Montreal Cognitive Assessment (MoCA) according to PASE scores; covariates included age, sex, Unified Parkinson’s Disease Rating Scale (UPDRS) part III score, and baseline MoCA.
A total of 379 patients completed at least one PASE questionnaire over the course of the study. PASE scores in this cohort have been previously described (Mantri S et al. J Park Dis. 2018;8[1]:107-11). Although overall rates of cognitive decline are known to be modest in this early cohort, PASE over time has a significant effect on MoCA during follow-up (P = 0.02) which suggest that higher levels of activity throughout disease are associated with better cognitive performance.
Dr. Mantri had nothing to disclose. Among her coauthors, Dr. Tropea received personal compensation from Genzyme and Medtronics and research support from Sanofi. Dr. Morley had nothing to disclose.
SOURCE: Mantri S et al. AAN 2019, Abstract P2.8-021.
REPORTING FROM AAN 2019
Key clinical point: Physical activity is associated with slower cognitive decline in patients with de novo Parkinson’s disease.
Major finding: Higher scores on the Physical Activity Scale for the Elderly over time had a significant effect on cognitive function.
Study details: A prospective study of 379 patients enrolled in the Parkinson’s Progression Markers Initiative.
Disclosures: Dr. Mantri had no relevant financial disclosures. Among her coauthors, Dr. Tropea received personal compensation from Genzyme and Medtronics and research support from Sanofi. Dr. Morley had nothing to disclose.
Source: Mantri S et al. AAN 2019, Abstract P2.8-021.
Cannabidiol reduces seizures in Dravet syndrome
Philadelphia – according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.
“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”
Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.
The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.
Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.
The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.
The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.
“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.
GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.
SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.
Philadelphia – according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.
“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”
Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.
The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.
Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.
The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.
The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.
“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.
GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.
SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.
Philadelphia – according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.
“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”
Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.
The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.
Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.
The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.
The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.
“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.
GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.
SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.
REPORTING FROM AAN 2019
Researchers examine vitamin D, skin pigmentation, and outcomes of pediatric MS
PHILADELPHIA – according to research described at the annual meeting of the American Academy of Neurology. Future research will be required to understand the interactions between dietary vitamin D ingestion, sun exposure, pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and the genetic influences of vitamin D pathways with MS risk.
Race, vitamin D status, HLA-DRB1*15 genotype, and place of residence during childhood all affect the risk of MS. The place of residence also can affect exposure to ultraviolet radiation and, thus, dermal pigmentation.
Candice Dunn, a clinical research coordinator at the Children’s Hospital of Philadelphia, and colleagues conducted a prospective study to determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25[OH]D) levels measured at baseline, and skin tone are associated with MS outcome in children with ADS. They enrolled 259 children with incident ADS in a multisite study in Toronto and Philadelphia (latitudes 43° to 51°). The investigators measured non–sun-exposed upper inner arm melanin content using the DSM II ColorMeter device. They measured 25(OH)D concentrations in serum obtained within 60 days of symptom onset and compared them with laboratory-reported normative values. Vitamin D insufficiency was defined as 25(OH)D less than 75 nmol/L. Ms. Dunn and colleagues quantified HLA-DRB1*15 alleles using allele-specific polymerase chain reaction amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.
In all, 68 children were diagnosed with MS, 191 remained monophasic (monoADS). Approximately 46% of children with MS were HLA-DRB1*15-positive, compared with 29.9% of monoADS children. In addition, children with MS had significantly lower 25(OH)D levels (mean, 45.4 nmol/L) than monoADS children (mean, 61.9 nmol/L) at baseline. Non–sun-exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (mean melanin index, 46.4) and monoADS (mean melanin index, 43.5). Furthermore, 25(OH)D levels correlated with upper inner arm melanin index in the MS group, but not in children with monoADS.
Ms. Dunn had nothing to disclose, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
SOURCE: Dunn C et al. AAN 2019, Abstract S19.007.
PHILADELPHIA – according to research described at the annual meeting of the American Academy of Neurology. Future research will be required to understand the interactions between dietary vitamin D ingestion, sun exposure, pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and the genetic influences of vitamin D pathways with MS risk.
Race, vitamin D status, HLA-DRB1*15 genotype, and place of residence during childhood all affect the risk of MS. The place of residence also can affect exposure to ultraviolet radiation and, thus, dermal pigmentation.
Candice Dunn, a clinical research coordinator at the Children’s Hospital of Philadelphia, and colleagues conducted a prospective study to determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25[OH]D) levels measured at baseline, and skin tone are associated with MS outcome in children with ADS. They enrolled 259 children with incident ADS in a multisite study in Toronto and Philadelphia (latitudes 43° to 51°). The investigators measured non–sun-exposed upper inner arm melanin content using the DSM II ColorMeter device. They measured 25(OH)D concentrations in serum obtained within 60 days of symptom onset and compared them with laboratory-reported normative values. Vitamin D insufficiency was defined as 25(OH)D less than 75 nmol/L. Ms. Dunn and colleagues quantified HLA-DRB1*15 alleles using allele-specific polymerase chain reaction amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.
In all, 68 children were diagnosed with MS, 191 remained monophasic (monoADS). Approximately 46% of children with MS were HLA-DRB1*15-positive, compared with 29.9% of monoADS children. In addition, children with MS had significantly lower 25(OH)D levels (mean, 45.4 nmol/L) than monoADS children (mean, 61.9 nmol/L) at baseline. Non–sun-exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (mean melanin index, 46.4) and monoADS (mean melanin index, 43.5). Furthermore, 25(OH)D levels correlated with upper inner arm melanin index in the MS group, but not in children with monoADS.
Ms. Dunn had nothing to disclose, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
SOURCE: Dunn C et al. AAN 2019, Abstract S19.007.
PHILADELPHIA – according to research described at the annual meeting of the American Academy of Neurology. Future research will be required to understand the interactions between dietary vitamin D ingestion, sun exposure, pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and the genetic influences of vitamin D pathways with MS risk.
Race, vitamin D status, HLA-DRB1*15 genotype, and place of residence during childhood all affect the risk of MS. The place of residence also can affect exposure to ultraviolet radiation and, thus, dermal pigmentation.
Candice Dunn, a clinical research coordinator at the Children’s Hospital of Philadelphia, and colleagues conducted a prospective study to determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25[OH]D) levels measured at baseline, and skin tone are associated with MS outcome in children with ADS. They enrolled 259 children with incident ADS in a multisite study in Toronto and Philadelphia (latitudes 43° to 51°). The investigators measured non–sun-exposed upper inner arm melanin content using the DSM II ColorMeter device. They measured 25(OH)D concentrations in serum obtained within 60 days of symptom onset and compared them with laboratory-reported normative values. Vitamin D insufficiency was defined as 25(OH)D less than 75 nmol/L. Ms. Dunn and colleagues quantified HLA-DRB1*15 alleles using allele-specific polymerase chain reaction amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.
In all, 68 children were diagnosed with MS, 191 remained monophasic (monoADS). Approximately 46% of children with MS were HLA-DRB1*15-positive, compared with 29.9% of monoADS children. In addition, children with MS had significantly lower 25(OH)D levels (mean, 45.4 nmol/L) than monoADS children (mean, 61.9 nmol/L) at baseline. Non–sun-exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (mean melanin index, 46.4) and monoADS (mean melanin index, 43.5). Furthermore, 25(OH)D levels correlated with upper inner arm melanin index in the MS group, but not in children with monoADS.
Ms. Dunn had nothing to disclose, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
SOURCE: Dunn C et al. AAN 2019, Abstract S19.007.
REPORTING FROM AAN 2019
Key clinical point: The relationship between vitamin D status and MS outcome in children relates to skin pigmentation.
Major finding: About 46% of children with MS were HLA-DRB1*15 positive.
Study details: A multisite, prospective study of 259 children with MS.
Disclosures: Ms. Dunn had no disclosures, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
Source: Dunn C et al. AAN 2019, Abstract S19.007.
Guideline issued for treating Tourette syndrome and chronic tics
PHILADELPHIA – Approaches to managing tics in patients with Tourette syndrome or chronic tic disorders “should be individualized, and the choice should be the result of a collaborative decision among patient, caregiver, and clinician, during which the benefits and harms of individual treatments as well as the presence of comorbid disorders are considered,” according to Tamara Pringsheim, MD, lead author of a practice guideline published May 6, 2019, by the American Academy of Neurology, and her collaborators.
The panel of nine physicians, two psychologists, and two patient representatives developed the recommendations based on a comprehensive systematic literature review. They concluded that treatments may decrease the frequency and severity of tics but rarely eliminate them.
The guideline was endorsed by the Child Neurology Society and the European Academy of Neurology and is the first such guideline for American neurologists, said Dr. Pringsheim of the University of Calgary (Alta.). Like recent Canadian and European guidelines, it strongly supports the Comprehensive Behavioral Intervention for Tics (CBIT) as a treatment option for tics.
After examining which medical, behavioral, and neurostimulation interventions, compared with placebo or other active interventions, improve tic severity and tic-related impairment in children and adults with Tourette syndrome or a chronic tic disorder, the guideline writers recommended that the evidence was strongest for CBIT as a first-line treatment, relative to other behavioral treatments and medications.
If symptoms affect a patient’s daily life, doctors should consider CBIT, said guideline author John Piacentini, PhD, of the University of California, Los Angeles, at the annual meeting of the American Academy of Neurology. “This treatment combines habit-reversal training, which teaches patients how to control their urges to tic, with other behavioral strategies to reduce stress and other factors that often make tics worse.”
Patients typically see results from CBIT in 8-12 weeks. More CBIT providers are needed, however, to make the treatment readily available to all patients, he said.
The guideline panel members said that there was moderate confidence in the evidence for reduced tic severity for the following therapeutic approaches, compared with placebo: haloperidol, risperidone, aripiprazole (children only), tiapride (children only), clonidine, onabotulinumtoxinA injections, ningdong granule (as formulated by Zhao), (children only), and ling granule (children only). There was low or very low confidence in the evidence for all other therapies for reducing tic severity.
Comorbid conditions
Many people with tic disorders have neurodevelopmental or psychiatric conditions such as ADHD, obsessive-compulsive disorder, and mood and anxiety disorders. The guideline recommends that people with tics be evaluated for these conditions.
Alpha2-adrenergic agonists may improve symptoms of tic disorders and ADHD, the authors said. There was moderate confidence in the evidence for reduced tic severity for people with a comorbid diagnosis of ADHD with clonidine plus methylphenidate (children only) and methylphenidate alone (children only), compared with placebo.
Adults with severe Tourette syndrome who are resistant to medical and behavioral therapy may benefit from deep brain stimulation (DBS), the guideline states. There was moderate confidence in the evidence for reduced tic severity for DBS of the globus pallidus, compared with sham DBS, as an option for adults with severe tics who have failed CBIT and drugs. These patients first must be screened by a mental health professional and continue to be monitored throughout DBS treatment.
Adults with Tourette syndrome who self-treat their tics with cannabis in states where cannabis is legal should see a doctor who can monitor the use of cannabis for efficacy and adverse effects, the guideline says.
Adverse effects of therapy
The panel also examined the risks of harm, including weight gain, elevated prolactin levels, sedation, drug-induced movement disorders, hypotension, bradycardia, and ECG changes with medical treatments, compared with placebo or other active interventions. In regard to weight gain, the panel concluded with moderate confidence that people with tics receiving risperidone or aripiprazole (children only) are probably more likely to gain weight than people receiving placebo. There was low confidence for associations between specific therapies and elevated prolactin levels.
Compared with people receiving placebo, there was moderate confidence that tiapride is probably associated with higher rates of physical tiredness and sleep disturbances (children only), that clonidine is probably associated with sedation, and that guanfacine is probably associated with drowsiness (children only). There was moderate evidence that pimozide is probably associated with extrapyramidal symptoms. There was low confidence that any specific treatment led to hypotension, bradycardia, or ECG changes.
Additional guideline specifics
The guideline’s practice recommendations include explaining the natural history of tic disorders to patients and caregivers and evaluating patients for functional impairment. Watchful waiting is an acceptable approach in people who do not experience functional impairment, and patients receiving medications for tics must have periodic reevaluations for the need for ongoing medical treatment. People with Tourette syndrome should be referred to resources for psychoeducation for teachers and peers, such as the Tourette Association of America.
Comorbid ADHD occurs in 30%-50% of patients with tics. If screening for ADHD is positive, the burden of ADHD symptoms should be assessed and those with functionally impairing ADHD should be treated for the disorder. Similarly, obsessive-compulsive behaviors occur in 10%-50% of those with Tourette syndrome. If an assessment finds comorbid obsessive-compulsive disorder, it should be treated.
Other psychiatric comorbidities with Tourette syndrome include anxiety disorders, oppositional defiant disorder, and mood disorders. When screening for these conditions, one must inquire about suicidal thoughts and suicide attempts and refer to appropriate resources if present, according to the guidelines.
Individuals with tics and comorbid ADHD should be advised that alpha2-adrenergic agonists may provide benefit for both conditions. Alpha2-adrenergic agonists should be prescribed for the treatment of tics when the benefits of treatment outweigh the risks and patients must be counseled regarding common side effects of alpha2-adrenergic agonists, including sedation. Heart rate and blood pressure must be monitored in patients with tics treated with alpha2-adrenergic agonists. If prescribing extended-release guanfacine, one must monitor the QTc interval in patients with a history of cardiac conditions, patients taking other QT-prolonging agents, or patients with a family history of long QT syndrome. If discontinuing alpha2-adrenergic agonists, they must gradually be tapered to avoid rebound hypertension.
If considering antipsychotic therapies, patients must be counseled on the relative risk for extrapyramidal, hormonal, and metabolic adverse effects to inform decision making on which antipsychotic should be prescribed. Before prescribing antipsychotics for tics, ECGs must be performed. The QTc interval must be measured before and after starting pimozide or ziprasidone, or if antipsychotics are coadministered with other drugs that can prolong the QT interval. The lowest effective dose should be prescribed to decrease the risk of adverse effects, and patients should be monitored for drug-induced movement disorders and for metabolic and hormonal adverse effects of antipsychotics. When attempting to discontinue antipsychotics for tics, the medications should be gradually tapered over weeks to months to avoid withdrawal dyskinesias.
If topiramate is prescribed, patients must be counseled regarding common adverse effects, including cognitive and language problems, somnolence, weight loss, and an increased risk of renal stones.
Some patients with Tourette syndrome use cannabis as a self-medication for tics and comorbidities. Because of the risks associated with cannabis use and widespread self-medication with cannabis for tics, where regional legislation and resources allow, physicians must offer to direct patients to appropriate medical supervision when cannabis is used as self-medication for tics. Appropriate medical supervision would entail education and monitoring for efficacy and adverse effects, according to the guidelines.
Where regional legislation allows, physicians prescribing cannabis-based medication must prescribe the lowest effective dose to decrease the risk of adverse effects. Physicians prescribing cannabis-based medication must inform patients that medication may impair driving ability. Physicians prescribing cannabis-based medication to patients with Tourette syndrome must periodically reevaluate the need for ongoing treatment.
A multidisciplinary evaluation is needed to establish when the benefits of treatment outweigh the risks for prescribing DBS for medication-resistant motor and phonic tics. The DSM-5 diagnosis of Tourette syndrome must be confirmed and exclude secondary and functional tic-like movements when considering DBS for medication-resistant tics. A mental health professional must screen patients preoperatively and follow patients postoperatively for psychiatric disorders that may impede the long-term success of the therapy. Physicians must confirm that multiple classes of medication (antipsychotics, dopamine depleters, alpha1 agonists) and behavioral therapy have been administered (or are contraindicated) before prescribing DBS for tics.
The practice guideline was developed with financial support from AAN. Dr. Pringsheim reported no disclosures. Dr. Piacentini reported receiving funding for travel and speaking from foundations and universities and has received royalties from publishers. In addition, he has performed behavior therapy for tics for approximately 50% of his clinical time and has received financial or material support from Pfizer, the National Institute of Mental Health, and foundations.
SOURCE: Pringsheim T et al. Neurology. 2019 May 6. doi: 10.1212/WNL.0000000000007466.
PHILADELPHIA – Approaches to managing tics in patients with Tourette syndrome or chronic tic disorders “should be individualized, and the choice should be the result of a collaborative decision among patient, caregiver, and clinician, during which the benefits and harms of individual treatments as well as the presence of comorbid disorders are considered,” according to Tamara Pringsheim, MD, lead author of a practice guideline published May 6, 2019, by the American Academy of Neurology, and her collaborators.
The panel of nine physicians, two psychologists, and two patient representatives developed the recommendations based on a comprehensive systematic literature review. They concluded that treatments may decrease the frequency and severity of tics but rarely eliminate them.
The guideline was endorsed by the Child Neurology Society and the European Academy of Neurology and is the first such guideline for American neurologists, said Dr. Pringsheim of the University of Calgary (Alta.). Like recent Canadian and European guidelines, it strongly supports the Comprehensive Behavioral Intervention for Tics (CBIT) as a treatment option for tics.
After examining which medical, behavioral, and neurostimulation interventions, compared with placebo or other active interventions, improve tic severity and tic-related impairment in children and adults with Tourette syndrome or a chronic tic disorder, the guideline writers recommended that the evidence was strongest for CBIT as a first-line treatment, relative to other behavioral treatments and medications.
If symptoms affect a patient’s daily life, doctors should consider CBIT, said guideline author John Piacentini, PhD, of the University of California, Los Angeles, at the annual meeting of the American Academy of Neurology. “This treatment combines habit-reversal training, which teaches patients how to control their urges to tic, with other behavioral strategies to reduce stress and other factors that often make tics worse.”
Patients typically see results from CBIT in 8-12 weeks. More CBIT providers are needed, however, to make the treatment readily available to all patients, he said.
The guideline panel members said that there was moderate confidence in the evidence for reduced tic severity for the following therapeutic approaches, compared with placebo: haloperidol, risperidone, aripiprazole (children only), tiapride (children only), clonidine, onabotulinumtoxinA injections, ningdong granule (as formulated by Zhao), (children only), and ling granule (children only). There was low or very low confidence in the evidence for all other therapies for reducing tic severity.
Comorbid conditions
Many people with tic disorders have neurodevelopmental or psychiatric conditions such as ADHD, obsessive-compulsive disorder, and mood and anxiety disorders. The guideline recommends that people with tics be evaluated for these conditions.
Alpha2-adrenergic agonists may improve symptoms of tic disorders and ADHD, the authors said. There was moderate confidence in the evidence for reduced tic severity for people with a comorbid diagnosis of ADHD with clonidine plus methylphenidate (children only) and methylphenidate alone (children only), compared with placebo.
Adults with severe Tourette syndrome who are resistant to medical and behavioral therapy may benefit from deep brain stimulation (DBS), the guideline states. There was moderate confidence in the evidence for reduced tic severity for DBS of the globus pallidus, compared with sham DBS, as an option for adults with severe tics who have failed CBIT and drugs. These patients first must be screened by a mental health professional and continue to be monitored throughout DBS treatment.
Adults with Tourette syndrome who self-treat their tics with cannabis in states where cannabis is legal should see a doctor who can monitor the use of cannabis for efficacy and adverse effects, the guideline says.
Adverse effects of therapy
The panel also examined the risks of harm, including weight gain, elevated prolactin levels, sedation, drug-induced movement disorders, hypotension, bradycardia, and ECG changes with medical treatments, compared with placebo or other active interventions. In regard to weight gain, the panel concluded with moderate confidence that people with tics receiving risperidone or aripiprazole (children only) are probably more likely to gain weight than people receiving placebo. There was low confidence for associations between specific therapies and elevated prolactin levels.
Compared with people receiving placebo, there was moderate confidence that tiapride is probably associated with higher rates of physical tiredness and sleep disturbances (children only), that clonidine is probably associated with sedation, and that guanfacine is probably associated with drowsiness (children only). There was moderate evidence that pimozide is probably associated with extrapyramidal symptoms. There was low confidence that any specific treatment led to hypotension, bradycardia, or ECG changes.
Additional guideline specifics
The guideline’s practice recommendations include explaining the natural history of tic disorders to patients and caregivers and evaluating patients for functional impairment. Watchful waiting is an acceptable approach in people who do not experience functional impairment, and patients receiving medications for tics must have periodic reevaluations for the need for ongoing medical treatment. People with Tourette syndrome should be referred to resources for psychoeducation for teachers and peers, such as the Tourette Association of America.
Comorbid ADHD occurs in 30%-50% of patients with tics. If screening for ADHD is positive, the burden of ADHD symptoms should be assessed and those with functionally impairing ADHD should be treated for the disorder. Similarly, obsessive-compulsive behaviors occur in 10%-50% of those with Tourette syndrome. If an assessment finds comorbid obsessive-compulsive disorder, it should be treated.
Other psychiatric comorbidities with Tourette syndrome include anxiety disorders, oppositional defiant disorder, and mood disorders. When screening for these conditions, one must inquire about suicidal thoughts and suicide attempts and refer to appropriate resources if present, according to the guidelines.
Individuals with tics and comorbid ADHD should be advised that alpha2-adrenergic agonists may provide benefit for both conditions. Alpha2-adrenergic agonists should be prescribed for the treatment of tics when the benefits of treatment outweigh the risks and patients must be counseled regarding common side effects of alpha2-adrenergic agonists, including sedation. Heart rate and blood pressure must be monitored in patients with tics treated with alpha2-adrenergic agonists. If prescribing extended-release guanfacine, one must monitor the QTc interval in patients with a history of cardiac conditions, patients taking other QT-prolonging agents, or patients with a family history of long QT syndrome. If discontinuing alpha2-adrenergic agonists, they must gradually be tapered to avoid rebound hypertension.
If considering antipsychotic therapies, patients must be counseled on the relative risk for extrapyramidal, hormonal, and metabolic adverse effects to inform decision making on which antipsychotic should be prescribed. Before prescribing antipsychotics for tics, ECGs must be performed. The QTc interval must be measured before and after starting pimozide or ziprasidone, or if antipsychotics are coadministered with other drugs that can prolong the QT interval. The lowest effective dose should be prescribed to decrease the risk of adverse effects, and patients should be monitored for drug-induced movement disorders and for metabolic and hormonal adverse effects of antipsychotics. When attempting to discontinue antipsychotics for tics, the medications should be gradually tapered over weeks to months to avoid withdrawal dyskinesias.
If topiramate is prescribed, patients must be counseled regarding common adverse effects, including cognitive and language problems, somnolence, weight loss, and an increased risk of renal stones.
Some patients with Tourette syndrome use cannabis as a self-medication for tics and comorbidities. Because of the risks associated with cannabis use and widespread self-medication with cannabis for tics, where regional legislation and resources allow, physicians must offer to direct patients to appropriate medical supervision when cannabis is used as self-medication for tics. Appropriate medical supervision would entail education and monitoring for efficacy and adverse effects, according to the guidelines.
Where regional legislation allows, physicians prescribing cannabis-based medication must prescribe the lowest effective dose to decrease the risk of adverse effects. Physicians prescribing cannabis-based medication must inform patients that medication may impair driving ability. Physicians prescribing cannabis-based medication to patients with Tourette syndrome must periodically reevaluate the need for ongoing treatment.
A multidisciplinary evaluation is needed to establish when the benefits of treatment outweigh the risks for prescribing DBS for medication-resistant motor and phonic tics. The DSM-5 diagnosis of Tourette syndrome must be confirmed and exclude secondary and functional tic-like movements when considering DBS for medication-resistant tics. A mental health professional must screen patients preoperatively and follow patients postoperatively for psychiatric disorders that may impede the long-term success of the therapy. Physicians must confirm that multiple classes of medication (antipsychotics, dopamine depleters, alpha1 agonists) and behavioral therapy have been administered (or are contraindicated) before prescribing DBS for tics.
The practice guideline was developed with financial support from AAN. Dr. Pringsheim reported no disclosures. Dr. Piacentini reported receiving funding for travel and speaking from foundations and universities and has received royalties from publishers. In addition, he has performed behavior therapy for tics for approximately 50% of his clinical time and has received financial or material support from Pfizer, the National Institute of Mental Health, and foundations.
SOURCE: Pringsheim T et al. Neurology. 2019 May 6. doi: 10.1212/WNL.0000000000007466.
PHILADELPHIA – Approaches to managing tics in patients with Tourette syndrome or chronic tic disorders “should be individualized, and the choice should be the result of a collaborative decision among patient, caregiver, and clinician, during which the benefits and harms of individual treatments as well as the presence of comorbid disorders are considered,” according to Tamara Pringsheim, MD, lead author of a practice guideline published May 6, 2019, by the American Academy of Neurology, and her collaborators.
The panel of nine physicians, two psychologists, and two patient representatives developed the recommendations based on a comprehensive systematic literature review. They concluded that treatments may decrease the frequency and severity of tics but rarely eliminate them.
The guideline was endorsed by the Child Neurology Society and the European Academy of Neurology and is the first such guideline for American neurologists, said Dr. Pringsheim of the University of Calgary (Alta.). Like recent Canadian and European guidelines, it strongly supports the Comprehensive Behavioral Intervention for Tics (CBIT) as a treatment option for tics.
After examining which medical, behavioral, and neurostimulation interventions, compared with placebo or other active interventions, improve tic severity and tic-related impairment in children and adults with Tourette syndrome or a chronic tic disorder, the guideline writers recommended that the evidence was strongest for CBIT as a first-line treatment, relative to other behavioral treatments and medications.
If symptoms affect a patient’s daily life, doctors should consider CBIT, said guideline author John Piacentini, PhD, of the University of California, Los Angeles, at the annual meeting of the American Academy of Neurology. “This treatment combines habit-reversal training, which teaches patients how to control their urges to tic, with other behavioral strategies to reduce stress and other factors that often make tics worse.”
Patients typically see results from CBIT in 8-12 weeks. More CBIT providers are needed, however, to make the treatment readily available to all patients, he said.
The guideline panel members said that there was moderate confidence in the evidence for reduced tic severity for the following therapeutic approaches, compared with placebo: haloperidol, risperidone, aripiprazole (children only), tiapride (children only), clonidine, onabotulinumtoxinA injections, ningdong granule (as formulated by Zhao), (children only), and ling granule (children only). There was low or very low confidence in the evidence for all other therapies for reducing tic severity.
Comorbid conditions
Many people with tic disorders have neurodevelopmental or psychiatric conditions such as ADHD, obsessive-compulsive disorder, and mood and anxiety disorders. The guideline recommends that people with tics be evaluated for these conditions.
Alpha2-adrenergic agonists may improve symptoms of tic disorders and ADHD, the authors said. There was moderate confidence in the evidence for reduced tic severity for people with a comorbid diagnosis of ADHD with clonidine plus methylphenidate (children only) and methylphenidate alone (children only), compared with placebo.
Adults with severe Tourette syndrome who are resistant to medical and behavioral therapy may benefit from deep brain stimulation (DBS), the guideline states. There was moderate confidence in the evidence for reduced tic severity for DBS of the globus pallidus, compared with sham DBS, as an option for adults with severe tics who have failed CBIT and drugs. These patients first must be screened by a mental health professional and continue to be monitored throughout DBS treatment.
Adults with Tourette syndrome who self-treat their tics with cannabis in states where cannabis is legal should see a doctor who can monitor the use of cannabis for efficacy and adverse effects, the guideline says.
Adverse effects of therapy
The panel also examined the risks of harm, including weight gain, elevated prolactin levels, sedation, drug-induced movement disorders, hypotension, bradycardia, and ECG changes with medical treatments, compared with placebo or other active interventions. In regard to weight gain, the panel concluded with moderate confidence that people with tics receiving risperidone or aripiprazole (children only) are probably more likely to gain weight than people receiving placebo. There was low confidence for associations between specific therapies and elevated prolactin levels.
Compared with people receiving placebo, there was moderate confidence that tiapride is probably associated with higher rates of physical tiredness and sleep disturbances (children only), that clonidine is probably associated with sedation, and that guanfacine is probably associated with drowsiness (children only). There was moderate evidence that pimozide is probably associated with extrapyramidal symptoms. There was low confidence that any specific treatment led to hypotension, bradycardia, or ECG changes.
Additional guideline specifics
The guideline’s practice recommendations include explaining the natural history of tic disorders to patients and caregivers and evaluating patients for functional impairment. Watchful waiting is an acceptable approach in people who do not experience functional impairment, and patients receiving medications for tics must have periodic reevaluations for the need for ongoing medical treatment. People with Tourette syndrome should be referred to resources for psychoeducation for teachers and peers, such as the Tourette Association of America.
Comorbid ADHD occurs in 30%-50% of patients with tics. If screening for ADHD is positive, the burden of ADHD symptoms should be assessed and those with functionally impairing ADHD should be treated for the disorder. Similarly, obsessive-compulsive behaviors occur in 10%-50% of those with Tourette syndrome. If an assessment finds comorbid obsessive-compulsive disorder, it should be treated.
Other psychiatric comorbidities with Tourette syndrome include anxiety disorders, oppositional defiant disorder, and mood disorders. When screening for these conditions, one must inquire about suicidal thoughts and suicide attempts and refer to appropriate resources if present, according to the guidelines.
Individuals with tics and comorbid ADHD should be advised that alpha2-adrenergic agonists may provide benefit for both conditions. Alpha2-adrenergic agonists should be prescribed for the treatment of tics when the benefits of treatment outweigh the risks and patients must be counseled regarding common side effects of alpha2-adrenergic agonists, including sedation. Heart rate and blood pressure must be monitored in patients with tics treated with alpha2-adrenergic agonists. If prescribing extended-release guanfacine, one must monitor the QTc interval in patients with a history of cardiac conditions, patients taking other QT-prolonging agents, or patients with a family history of long QT syndrome. If discontinuing alpha2-adrenergic agonists, they must gradually be tapered to avoid rebound hypertension.
If considering antipsychotic therapies, patients must be counseled on the relative risk for extrapyramidal, hormonal, and metabolic adverse effects to inform decision making on which antipsychotic should be prescribed. Before prescribing antipsychotics for tics, ECGs must be performed. The QTc interval must be measured before and after starting pimozide or ziprasidone, or if antipsychotics are coadministered with other drugs that can prolong the QT interval. The lowest effective dose should be prescribed to decrease the risk of adverse effects, and patients should be monitored for drug-induced movement disorders and for metabolic and hormonal adverse effects of antipsychotics. When attempting to discontinue antipsychotics for tics, the medications should be gradually tapered over weeks to months to avoid withdrawal dyskinesias.
If topiramate is prescribed, patients must be counseled regarding common adverse effects, including cognitive and language problems, somnolence, weight loss, and an increased risk of renal stones.
Some patients with Tourette syndrome use cannabis as a self-medication for tics and comorbidities. Because of the risks associated with cannabis use and widespread self-medication with cannabis for tics, where regional legislation and resources allow, physicians must offer to direct patients to appropriate medical supervision when cannabis is used as self-medication for tics. Appropriate medical supervision would entail education and monitoring for efficacy and adverse effects, according to the guidelines.
Where regional legislation allows, physicians prescribing cannabis-based medication must prescribe the lowest effective dose to decrease the risk of adverse effects. Physicians prescribing cannabis-based medication must inform patients that medication may impair driving ability. Physicians prescribing cannabis-based medication to patients with Tourette syndrome must periodically reevaluate the need for ongoing treatment.
A multidisciplinary evaluation is needed to establish when the benefits of treatment outweigh the risks for prescribing DBS for medication-resistant motor and phonic tics. The DSM-5 diagnosis of Tourette syndrome must be confirmed and exclude secondary and functional tic-like movements when considering DBS for medication-resistant tics. A mental health professional must screen patients preoperatively and follow patients postoperatively for psychiatric disorders that may impede the long-term success of the therapy. Physicians must confirm that multiple classes of medication (antipsychotics, dopamine depleters, alpha1 agonists) and behavioral therapy have been administered (or are contraindicated) before prescribing DBS for tics.
The practice guideline was developed with financial support from AAN. Dr. Pringsheim reported no disclosures. Dr. Piacentini reported receiving funding for travel and speaking from foundations and universities and has received royalties from publishers. In addition, he has performed behavior therapy for tics for approximately 50% of his clinical time and has received financial or material support from Pfizer, the National Institute of Mental Health, and foundations.
SOURCE: Pringsheim T et al. Neurology. 2019 May 6. doi: 10.1212/WNL.0000000000007466.
REPORTING FROM AAN 2019
Single-center study outlines stroke risk, DOAC type in nonvalvular AFib patients
PHILADELPHIA – A disproportionate number of breakthrough strokes were observed among patients receiving rivaroxaban for nonvalvular atrial fibrillation in a stroke unit, according to a small, single-center, retrospective study presented at the annual meeting of the American Academy of Neurology.
The researchers reviewed all patients presenting to a tertiary care stroke unit in Australia from January 2015 to June 2018.
A total of 56 patients (median age was 74 years; 61% were male) had received direct oral anticoagulant (DOAC) therapy and then had an ischemic stroke. Of those patients, 37 (66%) had strokes while receiving the treatment; 14 patients (25%) had a stroke after recently stopping a DOAC, often prior to a medical procedure; and 5 patients (9%) were not adherent to their DOAC regimen.
Of the 37 patients who had strokes during DOAC treatment, 48% were on rivaroxaban, 9% were on dabigatran, and 9% were on apixaban, Fiona Chan, MD, of The Princess Alexandra Hospital, Brisbane, Australia, and coinvestigators reported in a poster presentation.
While these findings need to be replicated in a larger study, they do “raise concern for inadequate stroke prevention within this cohort,” they said.
Moreover, the findings illustrate the importance of bridging anticoagulation prior to procedures, when appropriate, to minimize stroke risk, they added, as 25% of the strokes had occurred in patients who recently stopped the DOACs due to procedures.
To determine which DOAC was most often associated with breakthrough ischemic strokes in patients with nonvalvular atrial fibrillation, the investigators compared the proportion of DOACs prescribed in Australia to the proportion of observed strokes in their cohort.
Despite accounting for about 51% of Australian DOAC prescriptions, rivaroxaban represented nearly 73% of breakthrough strokes among the patients who had strokes while receiving the treatment (P = .001), the investigators reported.
Conversely, apixaban accounted for about 35% of prescriptions but 14% of the breakthrough strokes (P = .0007), while dabigatran accounted for 14% of prescriptions and 14% of the strokes (P = 0.99), the investigators said in their poster.
One limitation of this retrospective study is that the patient cohort came from a single specialized center, and may not reflect the true incidence of nonvalvular atrial fibrillation across Australia, the researchers noted.
Dr. Chan and coinvestigators reported that they had no relevant financial disclosures.
SOURCE: Chan F et al. AAN 2019. P1.3-001.
PHILADELPHIA – A disproportionate number of breakthrough strokes were observed among patients receiving rivaroxaban for nonvalvular atrial fibrillation in a stroke unit, according to a small, single-center, retrospective study presented at the annual meeting of the American Academy of Neurology.
The researchers reviewed all patients presenting to a tertiary care stroke unit in Australia from January 2015 to June 2018.
A total of 56 patients (median age was 74 years; 61% were male) had received direct oral anticoagulant (DOAC) therapy and then had an ischemic stroke. Of those patients, 37 (66%) had strokes while receiving the treatment; 14 patients (25%) had a stroke after recently stopping a DOAC, often prior to a medical procedure; and 5 patients (9%) were not adherent to their DOAC regimen.
Of the 37 patients who had strokes during DOAC treatment, 48% were on rivaroxaban, 9% were on dabigatran, and 9% were on apixaban, Fiona Chan, MD, of The Princess Alexandra Hospital, Brisbane, Australia, and coinvestigators reported in a poster presentation.
While these findings need to be replicated in a larger study, they do “raise concern for inadequate stroke prevention within this cohort,” they said.
Moreover, the findings illustrate the importance of bridging anticoagulation prior to procedures, when appropriate, to minimize stroke risk, they added, as 25% of the strokes had occurred in patients who recently stopped the DOACs due to procedures.
To determine which DOAC was most often associated with breakthrough ischemic strokes in patients with nonvalvular atrial fibrillation, the investigators compared the proportion of DOACs prescribed in Australia to the proportion of observed strokes in their cohort.
Despite accounting for about 51% of Australian DOAC prescriptions, rivaroxaban represented nearly 73% of breakthrough strokes among the patients who had strokes while receiving the treatment (P = .001), the investigators reported.
Conversely, apixaban accounted for about 35% of prescriptions but 14% of the breakthrough strokes (P = .0007), while dabigatran accounted for 14% of prescriptions and 14% of the strokes (P = 0.99), the investigators said in their poster.
One limitation of this retrospective study is that the patient cohort came from a single specialized center, and may not reflect the true incidence of nonvalvular atrial fibrillation across Australia, the researchers noted.
Dr. Chan and coinvestigators reported that they had no relevant financial disclosures.
SOURCE: Chan F et al. AAN 2019. P1.3-001.
PHILADELPHIA – A disproportionate number of breakthrough strokes were observed among patients receiving rivaroxaban for nonvalvular atrial fibrillation in a stroke unit, according to a small, single-center, retrospective study presented at the annual meeting of the American Academy of Neurology.
The researchers reviewed all patients presenting to a tertiary care stroke unit in Australia from January 2015 to June 2018.
A total of 56 patients (median age was 74 years; 61% were male) had received direct oral anticoagulant (DOAC) therapy and then had an ischemic stroke. Of those patients, 37 (66%) had strokes while receiving the treatment; 14 patients (25%) had a stroke after recently stopping a DOAC, often prior to a medical procedure; and 5 patients (9%) were not adherent to their DOAC regimen.
Of the 37 patients who had strokes during DOAC treatment, 48% were on rivaroxaban, 9% were on dabigatran, and 9% were on apixaban, Fiona Chan, MD, of The Princess Alexandra Hospital, Brisbane, Australia, and coinvestigators reported in a poster presentation.
While these findings need to be replicated in a larger study, they do “raise concern for inadequate stroke prevention within this cohort,” they said.
Moreover, the findings illustrate the importance of bridging anticoagulation prior to procedures, when appropriate, to minimize stroke risk, they added, as 25% of the strokes had occurred in patients who recently stopped the DOACs due to procedures.
To determine which DOAC was most often associated with breakthrough ischemic strokes in patients with nonvalvular atrial fibrillation, the investigators compared the proportion of DOACs prescribed in Australia to the proportion of observed strokes in their cohort.
Despite accounting for about 51% of Australian DOAC prescriptions, rivaroxaban represented nearly 73% of breakthrough strokes among the patients who had strokes while receiving the treatment (P = .001), the investigators reported.
Conversely, apixaban accounted for about 35% of prescriptions but 14% of the breakthrough strokes (P = .0007), while dabigatran accounted for 14% of prescriptions and 14% of the strokes (P = 0.99), the investigators said in their poster.
One limitation of this retrospective study is that the patient cohort came from a single specialized center, and may not reflect the true incidence of nonvalvular atrial fibrillation across Australia, the researchers noted.
Dr. Chan and coinvestigators reported that they had no relevant financial disclosures.
SOURCE: Chan F et al. AAN 2019. P1.3-001.
REPORTING FROM AAN 2019
Key clinical point: Rivaroxaban was associated with a disproportionate number of breakthrough strokes among patients with nonvalvular atrial fibrillation treated with direct oral anticoagulants at one stroke unit in Australia.
Major finding: Despite accounting for about 51% of Australian DOAC prescriptions, rivaroxaban represented nearly 73% of breakthrough strokes among the patients who had strokes while receiving treatment (P = .001).
Study details: Retrospective study of 56 patients with nonvalvular atrial fibrillation reporting to a tertiary care stroke unit in Australia.
Disclosures: The authors reported no financial disclosures.
Source: Chan F et al. AAN 019. Poster P1.3-001.