Migraine treatments such as magnesium, ondansetron, acetaminophen, and butalbital could be harmful if taken during pregnancy, according to a study published in the April issue of Current Neurology and Neuroscience Reports. Having a history of migraine could have serious effects on the health of a pregnancy and perinatal outcomes, making safe and effective treatment important. “Patients and doctors need to be aware that concerns exist and they should carefully weigh the risks and benefits of these treatments,” said Rebecca Erwin Wells, MD, MPH, Assistant Professor of Neurology at Wake Forest Baptist Health in Winston-Salem, North Carolina, and colleagues.

Rebecca Erwin Wells, MD, MPH

Magnesium

Magnesium was formerly considered the only safe supplement for migraine during pregnancy, but its safety was recently challenged by the FDA. Eighteen case reports in the FDA’s Adverse Event Reporting System raised new concerns about potential risks such as low calcium, bone abnormalities, and rickets-like skeletal abnormalities in neonates exposed to IV magnesium in utero. Magnesium sulfate is still indicated for prevention and control of seizures in pre-eclampsia and eclampsia, however. The FDA reclassified magnesium sulfate injection as pregnancy category D because of its potential teratogenic effects. More research is needed to further understand the safety of magnesium in migraine prevention.

Ondansetron

Ondansetron is a popular antiemetic treatment for pregnant mothers, but recent findings have raised new concerns about fetal and maternal safety. The FDA released warnings about the risk of serotonin syndrome and serious dysrhythmias that the drug entails. In an observational study, 176 pregnant women exposed to ondansetron were compared with those exposed to other antiemetics and nonteratogens. No increased risks of major malformations with ondansetron were found. A case–control study in 2012 found that ondansetron increased the risk of cleft palate in offspring. A Danish investigation involving 897,018 women who were pregnant between 1997 and 2010 revealed a doubling in the prevalence of cardiac malformations with ondansetron use, but the data were not statistically significant. In a report published in the New England Journal of Medicine, Danish researchers examined 609,385 pregnancies from 2004 to 2011 and found no increased risks of adverse fetal outcomes associated with ondansetron.

Acetaminophen

Acetaminophen has been considered one of the safest analgesics to use during pregnancy, and more than 65% of pregnant women in the United States use it. Recent evidence, however, suggests possible links between maternal acetaminophen use and pediatric development of attention deficit hyperactivity disorder (ADHD) and wheezing. A Danish National Birth Cohort study from 1996 to 2002 involving 64,322 live-born child and mother pairs indicated that acetaminophen use during pregnancy was associated with an increased risk of ADHD-like behavior, a diagnosis of hyperkinetic disorder, or ADHD medication use at seven years. The greatest risk was associated with use during multiple trimesters and for more than 20 weeks. The Norwegian Mother and Child Cohort Study (1999–2008) involved 2,919 same-sex sibling pairs of mothers who were evaluated for paracetamol exposure and psychomotor and behavior development. Children with more than 28 days of prenatal exposure to paracetamol had poorer gross motor development, communication, and externalizing/internalizing behavior and higher activity levels.

Another prospective study, however, reported no significant relationship between maternal acetaminophen use in the first half of pregnancy and child IQ or attention. Other studies have linked paracetamol exposure to an increased risk of pediatric wheezing and asthma. However, in an Italian prospective birth cohort study involving 3,538 children, researchers found that all such associations were explained by confounding factors such as age at delivery, smoking, siblings, and asthma or asthmatic bronchitis.

Butalbital

Butalbital has been considered an abortive treatment of choice for migraine during pregnancy. According to the National Birth Defects Prevention Study, however, butalbital is associated with a potential increase in congenital heart defects. In this study, which involved 21,090 infants exposed to butalbital and 8,373 unaffected controls, periconceptual butalbital use was linked to tetralogy of Fallot, pulmonary valve stenosis, and secundum-type atrial septum defect. The small sample size limited the study’s power.

Nonpharmacologic and Procedure-Based Treatments

Pregnant women who are concerned about the risks associated with magnesium, ondansetron, acetaminophen, butalbital, or other pharmacologic treatments can try nonpharmacologic treatments. Therapies such as relaxation training, biofeedback, and physical therapy can be helpful for treatment of migraines. Healthy habits such as having a balanced diet, avoiding alcohol, limiting caffeine consumption, staying properly hydrated, and getting adequate sleep and exercise can also aid in preventing migraines.

Procedure-based migraine treatment options include craniosacral therapy and acupuncture. Craniosacral therapy involves gentle maneuvers to address restrictions in the craniosacral system. Evidence for this treatment’s efficacy in migraine, however, is limited. Acupuncture is as effective as prophylactic drug treatment for preventing migraine, and could help minimize nausea and vomiting that accompany headaches. If migraines persist with nonpharmacologic treatments, other recommended pharmacologic options such as beta-blockers, tricyclic antidepressants, riboflavin, coenzyme Q10, and pyridoxine could be effective and safe treatments.

More research is necessary to understand all the potential risks for migraine treatments and to find the safest treatment options. Pregnant mothers are advised to consult their doctor before starting any migraine treatment.

—Erica Robinson

Migraine treatments such as magnesium, ondansetron, acetaminophen, and butalbital could be harmful if taken during pregnancy, according to a study published in the April issue of Current Neurology and Neuroscience Reports. Having a history of migraine could have serious effects on the health of a pregnancy and perinatal outcomes, making safe and effective treatment important. “Patients and doctors need to be aware that concerns exist and they should carefully weigh the risks and benefits of these treatments,” said Rebecca Erwin Wells, MD, MPH, Assistant Professor of Neurology at Wake Forest Baptist Health in Winston-Salem, North Carolina, and colleagues.

Rebecca Erwin Wells, MD, MPH

Magnesium

Magnesium was formerly considered the only safe supplement for migraine during pregnancy, but its safety was recently challenged by the FDA. Eighteen case reports in the FDA’s Adverse Event Reporting System raised new concerns about potential risks such as low calcium, bone abnormalities, and rickets-like skeletal abnormalities in neonates exposed to IV magnesium in utero. Magnesium sulfate is still indicated for prevention and control of seizures in pre-eclampsia and eclampsia, however. The FDA reclassified magnesium sulfate injection as pregnancy category D because of its potential teratogenic effects. More research is needed to further understand the safety of magnesium in migraine prevention.

Ondansetron

Ondansetron is a popular antiemetic treatment for pregnant mothers, but recent findings have raised new concerns about fetal and maternal safety. The FDA released warnings about the risk of serotonin syndrome and serious dysrhythmias that the drug entails. In an observational study, 176 pregnant women exposed to ondansetron were compared with those exposed to other antiemetics and nonteratogens. No increased risks of major malformations with ondansetron were found. A case–control study in 2012 found that ondansetron increased the risk of cleft palate in offspring. A Danish investigation involving 897,018 women who were pregnant between 1997 and 2010 revealed a doubling in the prevalence of cardiac malformations with ondansetron use, but the data were not statistically significant. In a report published in the New England Journal of Medicine, Danish researchers examined 609,385 pregnancies from 2004 to 2011 and found no increased risks of adverse fetal outcomes associated with ondansetron.

Acetaminophen

Acetaminophen has been considered one of the safest analgesics to use during pregnancy, and more than 65% of pregnant women in the United States use it. Recent evidence, however, suggests possible links between maternal acetaminophen use and pediatric development of attention deficit hyperactivity disorder (ADHD) and wheezing. A Danish National Birth Cohort study from 1996 to 2002 involving 64,322 live-born child and mother pairs indicated that acetaminophen use during pregnancy was associated with an increased risk of ADHD-like behavior, a diagnosis of hyperkinetic disorder, or ADHD medication use at seven years. The greatest risk was associated with use during multiple trimesters and for more than 20 weeks. The Norwegian Mother and Child Cohort Study (1999–2008) involved 2,919 same-sex sibling pairs of mothers who were evaluated for paracetamol exposure and psychomotor and behavior development. Children with more than 28 days of prenatal exposure to paracetamol had poorer gross motor development, communication, and externalizing/internalizing behavior and higher activity levels.

Another prospective study, however, reported no significant relationship between maternal acetaminophen use in the first half of pregnancy and child IQ or attention. Other studies have linked paracetamol exposure to an increased risk of pediatric wheezing and asthma. However, in an Italian prospective birth cohort study involving 3,538 children, researchers found that all such associations were explained by confounding factors such as age at delivery, smoking, siblings, and asthma or asthmatic bronchitis.

Butalbital

Butalbital has been considered an abortive treatment of choice for migraine during pregnancy. According to the National Birth Defects Prevention Study, however, butalbital is associated with a potential increase in congenital heart defects. In this study, which involved 21,090 infants exposed to butalbital and 8,373 unaffected controls, periconceptual butalbital use was linked to tetralogy of Fallot, pulmonary valve stenosis, and secundum-type atrial septum defect. The small sample size limited the study’s power.

Nonpharmacologic and Procedure-Based Treatments

Pregnant women who are concerned about the risks associated with magnesium, ondansetron, acetaminophen, butalbital, or other pharmacologic treatments can try nonpharmacologic treatments. Therapies such as relaxation training, biofeedback, and physical therapy can be helpful for treatment of migraines. Healthy habits such as having a balanced diet, avoiding alcohol, limiting caffeine consumption, staying properly hydrated, and getting adequate sleep and exercise can also aid in preventing migraines.

Procedure-based migraine treatment options include craniosacral therapy and acupuncture. Craniosacral therapy involves gentle maneuvers to address restrictions in the craniosacral system. Evidence for this treatment’s efficacy in migraine, however, is limited. Acupuncture is as effective as prophylactic drug treatment for preventing migraine, and could help minimize nausea and vomiting that accompany headaches. If migraines persist with nonpharmacologic treatments, other recommended pharmacologic options such as beta-blockers, tricyclic antidepressants, riboflavin, coenzyme Q10, and pyridoxine could be effective and safe treatments.

More research is necessary to understand all the potential risks for migraine treatments and to find the safest treatment options. Pregnant mothers are advised to consult their doctor before starting any migraine treatment.

—Erica Robinson

Migraine treatments such as magnesium, ondansetron, acetaminophen, and butalbital could be harmful if taken during pregnancy, according to a study published in the April issue of Current Neurology and Neuroscience Reports. Having a history of migraine could have serious effects on the health of a pregnancy and perinatal outcomes, making safe and effective treatment important. “Patients and doctors need to be aware that concerns exist and they should carefully weigh the risks and benefits of these treatments,” said Rebecca Erwin Wells, MD, MPH, Assistant Professor of Neurology at Wake Forest Baptist Health in Winston-Salem, North Carolina, and colleagues.

Rebecca Erwin Wells, MD, MPH

Magnesium

Magnesium was formerly considered the only safe supplement for migraine during pregnancy, but its safety was recently challenged by the FDA. Eighteen case reports in the FDA’s Adverse Event Reporting System raised new concerns about potential risks such as low calcium, bone abnormalities, and rickets-like skeletal abnormalities in neonates exposed to IV magnesium in utero. Magnesium sulfate is still indicated for prevention and control of seizures in pre-eclampsia and eclampsia, however. The FDA reclassified magnesium sulfate injection as pregnancy category D because of its potential teratogenic effects. More research is needed to further understand the safety of magnesium in migraine prevention.

Ondansetron

Ondansetron is a popular antiemetic treatment for pregnant mothers, but recent findings have raised new concerns about fetal and maternal safety. The FDA released warnings about the risk of serotonin syndrome and serious dysrhythmias that the drug entails. In an observational study, 176 pregnant women exposed to ondansetron were compared with those exposed to other antiemetics and nonteratogens. No increased risks of major malformations with ondansetron were found. A case–control study in 2012 found that ondansetron increased the risk of cleft palate in offspring. A Danish investigation involving 897,018 women who were pregnant between 1997 and 2010 revealed a doubling in the prevalence of cardiac malformations with ondansetron use, but the data were not statistically significant. In a report published in the New England Journal of Medicine, Danish researchers examined 609,385 pregnancies from 2004 to 2011 and found no increased risks of adverse fetal outcomes associated with ondansetron.

Acetaminophen

Acetaminophen has been considered one of the safest analgesics to use during pregnancy, and more than 65% of pregnant women in the United States use it. Recent evidence, however, suggests possible links between maternal acetaminophen use and pediatric development of attention deficit hyperactivity disorder (ADHD) and wheezing. A Danish National Birth Cohort study from 1996 to 2002 involving 64,322 live-born child and mother pairs indicated that acetaminophen use during pregnancy was associated with an increased risk of ADHD-like behavior, a diagnosis of hyperkinetic disorder, or ADHD medication use at seven years. The greatest risk was associated with use during multiple trimesters and for more than 20 weeks. The Norwegian Mother and Child Cohort Study (1999–2008) involved 2,919 same-sex sibling pairs of mothers who were evaluated for paracetamol exposure and psychomotor and behavior development. Children with more than 28 days of prenatal exposure to paracetamol had poorer gross motor development, communication, and externalizing/internalizing behavior and higher activity levels.

Another prospective study, however, reported no significant relationship between maternal acetaminophen use in the first half of pregnancy and child IQ or attention. Other studies have linked paracetamol exposure to an increased risk of pediatric wheezing and asthma. However, in an Italian prospective birth cohort study involving 3,538 children, researchers found that all such associations were explained by confounding factors such as age at delivery, smoking, siblings, and asthma or asthmatic bronchitis.

Butalbital

Butalbital has been considered an abortive treatment of choice for migraine during pregnancy. According to the National Birth Defects Prevention Study, however, butalbital is associated with a potential increase in congenital heart defects. In this study, which involved 21,090 infants exposed to butalbital and 8,373 unaffected controls, periconceptual butalbital use was linked to tetralogy of Fallot, pulmonary valve stenosis, and secundum-type atrial septum defect. The small sample size limited the study’s power.

Nonpharmacologic and Procedure-Based Treatments

Pregnant women who are concerned about the risks associated with magnesium, ondansetron, acetaminophen, butalbital, or other pharmacologic treatments can try nonpharmacologic treatments. Therapies such as relaxation training, biofeedback, and physical therapy can be helpful for treatment of migraines. Healthy habits such as having a balanced diet, avoiding alcohol, limiting caffeine consumption, staying properly hydrated, and getting adequate sleep and exercise can also aid in preventing migraines.

Procedure-based migraine treatment options include craniosacral therapy and acupuncture. Craniosacral therapy involves gentle maneuvers to address restrictions in the craniosacral system. Evidence for this treatment’s efficacy in migraine, however, is limited. Acupuncture is as effective as prophylactic drug treatment for preventing migraine, and could help minimize nausea and vomiting that accompany headaches. If migraines persist with nonpharmacologic treatments, other recommended pharmacologic options such as beta-blockers, tricyclic antidepressants, riboflavin, coenzyme Q10, and pyridoxine could be effective and safe treatments.

More research is necessary to understand all the potential risks for migraine treatments and to find the safest treatment options. Pregnant mothers are advised to consult their doctor before starting any migraine treatment.

—Erica Robinson

A new analysis of registry data from European countries does not support an association between prenatal exposure to lamotrigine monotherapy and risk of orofacial cleft and clubfoot, in contrast to signals from previous studies of the antiepileptic drug. The analysis was published online ahead of print April 6 in Neurology.

Helen Dolk, DrPH, Professor of Epidemiology and Health Services Research and Head of the Center for Maternal, Fetal, and Infant Research at the University of Ulster in Coleraine, Northern Ireland, and her colleagues analyzed data from 10.1 million births exposed to antiepileptic drugs, including lamotrigine as a monotherapy, during the first trimester between 1995 and 2011. The births were recorded in 21 population-based registries from 16 European countries. The outcomes of interest were major congenital malformations in general, as well as orofacial clefts and clubfoot.

Helen Dolk, DrPH

Assessment of all antiepileptic drug-exposed congenital malformation registrations revealed that 12% of pregnant registrants were exposed to lamotrigine monotherapy. An additional 7% were exposed to lamotrigine as part of polytherapy. A total of 77.1% of pregnant women exposed to lamotrigine monotherapy had a diagnosis of epilepsy. The proportion of lamotrigine monotherapy exposures increased during the study period.

A total of 147 babies exposed to lamotrigine monotherapy with congenital malformations not attributable to chromosomal irregularities were identified from the total sample. The odds ratio for having a child with orofacial clefts after exposure to lamotrigine monotherapy was 1.31. Based on these data, the authors estimated that exposure to lamotrigine would result in orofacial clefts in fewer than one in every 550 exposed babies.

The odds ratio for having a child with clubfoot after exposure to lamotrigine monotherapy was 1.83. Although the study results confirmed the statistically significant signal for an overall excess risk of clubfoot found in a previous study that analyzed births during 1995–2005, the investigators could not reproduce this result in an independent study population of 6.3 million births during 2005–2011. Lamotrigine monotherapy was not associated with significant differences in the risk for developing any other congenital malformations, the investigators said.

—William Perlman

A new analysis of registry data from European countries does not support an association between prenatal exposure to lamotrigine monotherapy and risk of orofacial cleft and clubfoot, in contrast to signals from previous studies of the antiepileptic drug. The analysis was published online ahead of print April 6 in Neurology.

Helen Dolk, DrPH, Professor of Epidemiology and Health Services Research and Head of the Center for Maternal, Fetal, and Infant Research at the University of Ulster in Coleraine, Northern Ireland, and her colleagues analyzed data from 10.1 million births exposed to antiepileptic drugs, including lamotrigine as a monotherapy, during the first trimester between 1995 and 2011. The births were recorded in 21 population-based registries from 16 European countries. The outcomes of interest were major congenital malformations in general, as well as orofacial clefts and clubfoot.

Helen Dolk, DrPH

Assessment of all antiepileptic drug-exposed congenital malformation registrations revealed that 12% of pregnant registrants were exposed to lamotrigine monotherapy. An additional 7% were exposed to lamotrigine as part of polytherapy. A total of 77.1% of pregnant women exposed to lamotrigine monotherapy had a diagnosis of epilepsy. The proportion of lamotrigine monotherapy exposures increased during the study period.

A total of 147 babies exposed to lamotrigine monotherapy with congenital malformations not attributable to chromosomal irregularities were identified from the total sample. The odds ratio for having a child with orofacial clefts after exposure to lamotrigine monotherapy was 1.31. Based on these data, the authors estimated that exposure to lamotrigine would result in orofacial clefts in fewer than one in every 550 exposed babies.

The odds ratio for having a child with clubfoot after exposure to lamotrigine monotherapy was 1.83. Although the study results confirmed the statistically significant signal for an overall excess risk of clubfoot found in a previous study that analyzed births during 1995–2005, the investigators could not reproduce this result in an independent study population of 6.3 million births during 2005–2011. Lamotrigine monotherapy was not associated with significant differences in the risk for developing any other congenital malformations, the investigators said.

—William Perlman

A new analysis of registry data from European countries does not support an association between prenatal exposure to lamotrigine monotherapy and risk of orofacial cleft and clubfoot, in contrast to signals from previous studies of the antiepileptic drug. The analysis was published online ahead of print April 6 in Neurology.

Helen Dolk, DrPH, Professor of Epidemiology and Health Services Research and Head of the Center for Maternal, Fetal, and Infant Research at the University of Ulster in Coleraine, Northern Ireland, and her colleagues analyzed data from 10.1 million births exposed to antiepileptic drugs, including lamotrigine as a monotherapy, during the first trimester between 1995 and 2011. The births were recorded in 21 population-based registries from 16 European countries. The outcomes of interest were major congenital malformations in general, as well as orofacial clefts and clubfoot.

Helen Dolk, DrPH

Assessment of all antiepileptic drug-exposed congenital malformation registrations revealed that 12% of pregnant registrants were exposed to lamotrigine monotherapy. An additional 7% were exposed to lamotrigine as part of polytherapy. A total of 77.1% of pregnant women exposed to lamotrigine monotherapy had a diagnosis of epilepsy. The proportion of lamotrigine monotherapy exposures increased during the study period.

A total of 147 babies exposed to lamotrigine monotherapy with congenital malformations not attributable to chromosomal irregularities were identified from the total sample. The odds ratio for having a child with orofacial clefts after exposure to lamotrigine monotherapy was 1.31. Based on these data, the authors estimated that exposure to lamotrigine would result in orofacial clefts in fewer than one in every 550 exposed babies.

The odds ratio for having a child with clubfoot after exposure to lamotrigine monotherapy was 1.83. Although the study results confirmed the statistically significant signal for an overall excess risk of clubfoot found in a previous study that analyzed births during 1995–2005, the investigators could not reproduce this result in an independent study population of 6.3 million births during 2005–2011. Lamotrigine monotherapy was not associated with significant differences in the risk for developing any other congenital malformations, the investigators said.

—William Perlman

Chromosomal deletion at 22q11.2 may increase the risk of Parkinson’s disease, particularly early-onset Parkinson’s disease, according to research published online ahead of print March 23 in the Lancet Neurology.

The association between Parkinson’s disease and chromosome 22q11.2 deletion syndrome could be important for patient management, with implications for identifying and managing comorbidities as well as for genetic counseling, said Kin Y. Mok, PhD, of the Department of Molecular Neuroscience at the University College London Institute of Neurology and the Division of Life Science at Hong Kong University of Science and Technology, and colleagues.

Deletion at 22q11.2 is among the most common interstitial deletions in humans and one of the strongest genetic risk factors for schizophrenia, the authors noted. The clinical phenotype of chromosome 22q11.2 deletion syndrome varies widely and can include cleft palate, dysmorphic facial features, cardiac defects, skeletal deformities, and learning disabilities. The deletions are inherited from a parent in 5% to 10% of cases and occur de novo in the remainder of cases.

An observational study by Butcher et al found an increased frequency of Parkinson’s disease in patients with chromosome 22q11.2 deletion syndrome, compared with controls. Few patients with chromosome 22q11.2 deletion syndrome developed Parkinson’s disease, however, indicating that other factors play a role.

Four Genome-Wide Association Studies

To establish the frequency of deletions spanning the 22q11.2 locus in idiopathic Parkinson’s disease, Dr. Mok and colleagues screened data from the following four large independent genome-wide association studies: the UK Wellcome Trust Case Control Consortium 2 Parkinson’s disease, the Dutch Parkinson’s Disease Genetics Consortium, the US National Institute on Aging, and the International Parkinson’s Disease Genomics Consortium.

The investigators conducted case–control association analysis to compare the proportions of 22q11.2 deletions between groups. They used Fisher’s exact test for the independent case–control studies and the Mantel–Haenszel test for the meta-analyses. In addition, they retrieved clinical details from the medical records of patients with Parkinson’s disease who had 22q11.2 deletions.

In all, they included data from 9,387 patients with Parkinson’s disease and 13,863 controls in their analysis. Eight patients with Parkinson’ disease and none of the controls had 22q11.2 deletions. Age at onset was available for 8,451 of the patients with Parkinson’s disease, including all of those with 22q11.2 deletions. Age at onset was lower in patients carrying a 22q11.2 deletion, compared with patients with Parkinson’s disease who were not carrying a deletion (mean age at onset, 42.1 vs 60.3).In addition, a deletion was present in more patients with early-onset Parkinson’s disease than with late-onset Parkinson’s disease. “Of the 1,014 patients with Parkinson’s disease with age at onset younger than 45 years, five (0.49%) had 22q11.2 deletions, compared with three (0.04%) of 7,437 with an age at onset of 45 years or older,” the researchers said.

None of the patients with a deletion presented with a diagnosis of chromosome 22q11.2 deletion syndrome or schizophrenia. “With hindsight, some cases had other features suggestive of 22q11.2 deletion syndrome, such as hypocalcemia, depression, fatigue, mental retardation, and cleft palate,” the researchers said.

“Clinicians should bear this uncommon 22q11.2 deletion in mind when a patient presents with early-onset Parkinson’s disease,” said Dr. Mok and colleagues. “Carriers of a 22q11.2 deletion are prone to many other potential comorbidities, and clinicians should actively investigate for these comorbidities when managing a patient with a 22q11.2 deletion and Parkinson’s disease.”

Although the 22q11.2 deletion is associated with two neuropsychiatric disorders, schizophrenia and Parkinson’s disease, it is not clear whether the deletion “is a single common pathogenic pathway or whether separate genetic defects within the 22q11.2 deletion contribute to the differing phenotypes,” the authors said.

Findings May Reflect Ascertainment Bias

The findings are based on a retrospective, combined analysis of four studies that might be heterogeneous, and the methods of case referral in those studies could have led to ascertainment bias. For instance, although a history of schizoaffective disorder was not an explicit exclusion criterion in the recruitment of patients with Parkinson’s disease, the UK Brain Bank excludes patients with neuroleptic treatment at onset of Parkinson’s disease, the investigators said. Furthermore, psychiatrists or other specialists likely would manage patients who carry the deletion and have severe psychiatric or systemic illness, making those patients potentially less likely to be referred to neurology recruitment centers.

“We should approach their findings with cautious optimism,” said Eng-King Tan, MBBS, Senior Consultant Neurologist at the National Neuroscience Institute at Singapore General Hospital and Professor at Duke-National University of Singapore Medical School, in an accompanying commentary. “The estimated prevalence of 22q11.2 deletion syndrome in the general population (0.024%) and that of a 22q deletion among patients with early-onset Parkinson’s disease (0.49%) are low. Hence, any large-scale effect on screening in the general population of patients with Parkinson’s disease will be small.” In addition, fewer than 20 patients with coexistent 22q11.2 deletion syndrome and Parkinson’s disease have been identified so far, and it is not clear why only 3% of patients with the syndrome develop Parkinson’s disease, said Dr. Tan. Nevertheless, the study will heighten clinicians’ vigilance “in looking for features of 22q11.2 deletion syndrome in patients with early-onset Parkinson’s disease, and in carefully considering Parkinson’s disease as a differential diagnosis in patients with 22q11.2 deletion syndrome even if these patients are on antipsychotic drugs.”

—Jake Remaly

Chromosomal deletion at 22q11.2 may increase the risk of Parkinson’s disease, particularly early-onset Parkinson’s disease, according to research published online ahead of print March 23 in the Lancet Neurology.

The association between Parkinson’s disease and chromosome 22q11.2 deletion syndrome could be important for patient management, with implications for identifying and managing comorbidities as well as for genetic counseling, said Kin Y. Mok, PhD, of the Department of Molecular Neuroscience at the University College London Institute of Neurology and the Division of Life Science at Hong Kong University of Science and Technology, and colleagues.

Deletion at 22q11.2 is among the most common interstitial deletions in humans and one of the strongest genetic risk factors for schizophrenia, the authors noted. The clinical phenotype of chromosome 22q11.2 deletion syndrome varies widely and can include cleft palate, dysmorphic facial features, cardiac defects, skeletal deformities, and learning disabilities. The deletions are inherited from a parent in 5% to 10% of cases and occur de novo in the remainder of cases.

An observational study by Butcher et al found an increased frequency of Parkinson’s disease in patients with chromosome 22q11.2 deletion syndrome, compared with controls. Few patients with chromosome 22q11.2 deletion syndrome developed Parkinson’s disease, however, indicating that other factors play a role.

Four Genome-Wide Association Studies

To establish the frequency of deletions spanning the 22q11.2 locus in idiopathic Parkinson’s disease, Dr. Mok and colleagues screened data from the following four large independent genome-wide association studies: the UK Wellcome Trust Case Control Consortium 2 Parkinson’s disease, the Dutch Parkinson’s Disease Genetics Consortium, the US National Institute on Aging, and the International Parkinson’s Disease Genomics Consortium.

The investigators conducted case–control association analysis to compare the proportions of 22q11.2 deletions between groups. They used Fisher’s exact test for the independent case–control studies and the Mantel–Haenszel test for the meta-analyses. In addition, they retrieved clinical details from the medical records of patients with Parkinson’s disease who had 22q11.2 deletions.

In all, they included data from 9,387 patients with Parkinson’s disease and 13,863 controls in their analysis. Eight patients with Parkinson’ disease and none of the controls had 22q11.2 deletions. Age at onset was available for 8,451 of the patients with Parkinson’s disease, including all of those with 22q11.2 deletions. Age at onset was lower in patients carrying a 22q11.2 deletion, compared with patients with Parkinson’s disease who were not carrying a deletion (mean age at onset, 42.1 vs 60.3).In addition, a deletion was present in more patients with early-onset Parkinson’s disease than with late-onset Parkinson’s disease. “Of the 1,014 patients with Parkinson’s disease with age at onset younger than 45 years, five (0.49%) had 22q11.2 deletions, compared with three (0.04%) of 7,437 with an age at onset of 45 years or older,” the researchers said.

None of the patients with a deletion presented with a diagnosis of chromosome 22q11.2 deletion syndrome or schizophrenia. “With hindsight, some cases had other features suggestive of 22q11.2 deletion syndrome, such as hypocalcemia, depression, fatigue, mental retardation, and cleft palate,” the researchers said.

“Clinicians should bear this uncommon 22q11.2 deletion in mind when a patient presents with early-onset Parkinson’s disease,” said Dr. Mok and colleagues. “Carriers of a 22q11.2 deletion are prone to many other potential comorbidities, and clinicians should actively investigate for these comorbidities when managing a patient with a 22q11.2 deletion and Parkinson’s disease.”

Although the 22q11.2 deletion is associated with two neuropsychiatric disorders, schizophrenia and Parkinson’s disease, it is not clear whether the deletion “is a single common pathogenic pathway or whether separate genetic defects within the 22q11.2 deletion contribute to the differing phenotypes,” the authors said.

Findings May Reflect Ascertainment Bias

The findings are based on a retrospective, combined analysis of four studies that might be heterogeneous, and the methods of case referral in those studies could have led to ascertainment bias. For instance, although a history of schizoaffective disorder was not an explicit exclusion criterion in the recruitment of patients with Parkinson’s disease, the UK Brain Bank excludes patients with neuroleptic treatment at onset of Parkinson’s disease, the investigators said. Furthermore, psychiatrists or other specialists likely would manage patients who carry the deletion and have severe psychiatric or systemic illness, making those patients potentially less likely to be referred to neurology recruitment centers.

“We should approach their findings with cautious optimism,” said Eng-King Tan, MBBS, Senior Consultant Neurologist at the National Neuroscience Institute at Singapore General Hospital and Professor at Duke-National University of Singapore Medical School, in an accompanying commentary. “The estimated prevalence of 22q11.2 deletion syndrome in the general population (0.024%) and that of a 22q deletion among patients with early-onset Parkinson’s disease (0.49%) are low. Hence, any large-scale effect on screening in the general population of patients with Parkinson’s disease will be small.” In addition, fewer than 20 patients with coexistent 22q11.2 deletion syndrome and Parkinson’s disease have been identified so far, and it is not clear why only 3% of patients with the syndrome develop Parkinson’s disease, said Dr. Tan. Nevertheless, the study will heighten clinicians’ vigilance “in looking for features of 22q11.2 deletion syndrome in patients with early-onset Parkinson’s disease, and in carefully considering Parkinson’s disease as a differential diagnosis in patients with 22q11.2 deletion syndrome even if these patients are on antipsychotic drugs.”

—Jake Remaly

Chromosomal deletion at 22q11.2 may increase the risk of Parkinson’s disease, particularly early-onset Parkinson’s disease, according to research published online ahead of print March 23 in the Lancet Neurology.

The association between Parkinson’s disease and chromosome 22q11.2 deletion syndrome could be important for patient management, with implications for identifying and managing comorbidities as well as for genetic counseling, said Kin Y. Mok, PhD, of the Department of Molecular Neuroscience at the University College London Institute of Neurology and the Division of Life Science at Hong Kong University of Science and Technology, and colleagues.

Deletion at 22q11.2 is among the most common interstitial deletions in humans and one of the strongest genetic risk factors for schizophrenia, the authors noted. The clinical phenotype of chromosome 22q11.2 deletion syndrome varies widely and can include cleft palate, dysmorphic facial features, cardiac defects, skeletal deformities, and learning disabilities. The deletions are inherited from a parent in 5% to 10% of cases and occur de novo in the remainder of cases.

An observational study by Butcher et al found an increased frequency of Parkinson’s disease in patients with chromosome 22q11.2 deletion syndrome, compared with controls. Few patients with chromosome 22q11.2 deletion syndrome developed Parkinson’s disease, however, indicating that other factors play a role.

Four Genome-Wide Association Studies

To establish the frequency of deletions spanning the 22q11.2 locus in idiopathic Parkinson’s disease, Dr. Mok and colleagues screened data from the following four large independent genome-wide association studies: the UK Wellcome Trust Case Control Consortium 2 Parkinson’s disease, the Dutch Parkinson’s Disease Genetics Consortium, the US National Institute on Aging, and the International Parkinson’s Disease Genomics Consortium.

The investigators conducted case–control association analysis to compare the proportions of 22q11.2 deletions between groups. They used Fisher’s exact test for the independent case–control studies and the Mantel–Haenszel test for the meta-analyses. In addition, they retrieved clinical details from the medical records of patients with Parkinson’s disease who had 22q11.2 deletions.

In all, they included data from 9,387 patients with Parkinson’s disease and 13,863 controls in their analysis. Eight patients with Parkinson’ disease and none of the controls had 22q11.2 deletions. Age at onset was available for 8,451 of the patients with Parkinson’s disease, including all of those with 22q11.2 deletions. Age at onset was lower in patients carrying a 22q11.2 deletion, compared with patients with Parkinson’s disease who were not carrying a deletion (mean age at onset, 42.1 vs 60.3).In addition, a deletion was present in more patients with early-onset Parkinson’s disease than with late-onset Parkinson’s disease. “Of the 1,014 patients with Parkinson’s disease with age at onset younger than 45 years, five (0.49%) had 22q11.2 deletions, compared with three (0.04%) of 7,437 with an age at onset of 45 years or older,” the researchers said.

None of the patients with a deletion presented with a diagnosis of chromosome 22q11.2 deletion syndrome or schizophrenia. “With hindsight, some cases had other features suggestive of 22q11.2 deletion syndrome, such as hypocalcemia, depression, fatigue, mental retardation, and cleft palate,” the researchers said.

“Clinicians should bear this uncommon 22q11.2 deletion in mind when a patient presents with early-onset Parkinson’s disease,” said Dr. Mok and colleagues. “Carriers of a 22q11.2 deletion are prone to many other potential comorbidities, and clinicians should actively investigate for these comorbidities when managing a patient with a 22q11.2 deletion and Parkinson’s disease.”

Although the 22q11.2 deletion is associated with two neuropsychiatric disorders, schizophrenia and Parkinson’s disease, it is not clear whether the deletion “is a single common pathogenic pathway or whether separate genetic defects within the 22q11.2 deletion contribute to the differing phenotypes,” the authors said.

Findings May Reflect Ascertainment Bias

The findings are based on a retrospective, combined analysis of four studies that might be heterogeneous, and the methods of case referral in those studies could have led to ascertainment bias. For instance, although a history of schizoaffective disorder was not an explicit exclusion criterion in the recruitment of patients with Parkinson’s disease, the UK Brain Bank excludes patients with neuroleptic treatment at onset of Parkinson’s disease, the investigators said. Furthermore, psychiatrists or other specialists likely would manage patients who carry the deletion and have severe psychiatric or systemic illness, making those patients potentially less likely to be referred to neurology recruitment centers.

“We should approach their findings with cautious optimism,” said Eng-King Tan, MBBS, Senior Consultant Neurologist at the National Neuroscience Institute at Singapore General Hospital and Professor at Duke-National University of Singapore Medical School, in an accompanying commentary. “The estimated prevalence of 22q11.2 deletion syndrome in the general population (0.024%) and that of a 22q deletion among patients with early-onset Parkinson’s disease (0.49%) are low. Hence, any large-scale effect on screening in the general population of patients with Parkinson’s disease will be small.” In addition, fewer than 20 patients with coexistent 22q11.2 deletion syndrome and Parkinson’s disease have been identified so far, and it is not clear why only 3% of patients with the syndrome develop Parkinson’s disease, said Dr. Tan. Nevertheless, the study will heighten clinicians’ vigilance “in looking for features of 22q11.2 deletion syndrome in patients with early-onset Parkinson’s disease, and in carefully considering Parkinson’s disease as a differential diagnosis in patients with 22q11.2 deletion syndrome even if these patients are on antipsychotic drugs.”

—Jake Remaly

A 12-item case-finding tool correctly classifies most people with migraine and chronic migraine, according to research published in the March issue of Cephalalgia. The tool, which is called Identify Chronic Migraine (ID-CM), classifies migraine with a sensitivity of 83.5% and a specificity of 88.5% and chronic migraine with a sensitivity of 80.6% and a specificity of 88.6%.

Migraine, and chronic migraine in particular, is underdiagnosed and undertreated, said Richard B. Lipton, MD, Vice Chair of Neurology at Albert Einstein College of Medicine in the Bronx, New York, and colleagues. The authors sought to develop a valid case-finding tool for chronic migraine that would be applicable to people who reported severe headache.

Richard B. Lipton, MD

The researchers developed their instrument in four stages. In the first stage, they convened an international panel of expert clinicians and researchers that selected potential items from existing diagnostic tools. The panel also suggested additional items for consideration. In stage two, Dr. Lipton and colleagues conducted cognitive debriefing interviews with people with chronic migraine to determine whether the latter understood the tool’s instructions and whether the items were worded properly.

Researchers also administered the items that had emerged from stage two, along with a set of patient-reported outcome measures, to a Web-based sample of 1,600 people with migraine or other severe headache. Data from this stage enabled them to perform a psychometric assessment of the new tool’s candidate items. Finally, in stage four, investigators compared diagnoses assigned using ID-CM with independent diagnoses assigned by headache experts using a semistructured diagnostic interview for migraine. Patients who had participated in the third stage of development were invited to participate in this stage.

The final version of ID-CM includes two questions about headache frequency, four about headache symptoms, two about medication use, two about whether headache interferes with activities, and two about whether headache interferes with making plans.

“ID-CM has been rigorously evaluated and has strong psychometric properties and high classification accuracy, both for migraine and chronic migraine,” said Dr. Lipton. “Compared with other well-known and highly regarded screening and diagnostic tools for various diseases/disorders, the classification accuracy of ID-CM was both absolutely and relatively strong....The simplicity and accuracy of ID-CM will enable health care professionals with or without training in neurology, pain, or headache to correctly identify the majority of patients with migraine or chronic migraine,” Dr. Lipton said. “Clinicians will then be able to accurately diagnose or refer affected patients to specialists for effective treatment that will reduce the burden of illness experienced by those with migraine and chronic migraine.”

—Erik Greb

A 12-item case-finding tool correctly classifies most people with migraine and chronic migraine, according to research published in the March issue of Cephalalgia. The tool, which is called Identify Chronic Migraine (ID-CM), classifies migraine with a sensitivity of 83.5% and a specificity of 88.5% and chronic migraine with a sensitivity of 80.6% and a specificity of 88.6%.

Migraine, and chronic migraine in particular, is underdiagnosed and undertreated, said Richard B. Lipton, MD, Vice Chair of Neurology at Albert Einstein College of Medicine in the Bronx, New York, and colleagues. The authors sought to develop a valid case-finding tool for chronic migraine that would be applicable to people who reported severe headache.

Richard B. Lipton, MD

The researchers developed their instrument in four stages. In the first stage, they convened an international panel of expert clinicians and researchers that selected potential items from existing diagnostic tools. The panel also suggested additional items for consideration. In stage two, Dr. Lipton and colleagues conducted cognitive debriefing interviews with people with chronic migraine to determine whether the latter understood the tool’s instructions and whether the items were worded properly.

Researchers also administered the items that had emerged from stage two, along with a set of patient-reported outcome measures, to a Web-based sample of 1,600 people with migraine or other severe headache. Data from this stage enabled them to perform a psychometric assessment of the new tool’s candidate items. Finally, in stage four, investigators compared diagnoses assigned using ID-CM with independent diagnoses assigned by headache experts using a semistructured diagnostic interview for migraine. Patients who had participated in the third stage of development were invited to participate in this stage.

The final version of ID-CM includes two questions about headache frequency, four about headache symptoms, two about medication use, two about whether headache interferes with activities, and two about whether headache interferes with making plans.

“ID-CM has been rigorously evaluated and has strong psychometric properties and high classification accuracy, both for migraine and chronic migraine,” said Dr. Lipton. “Compared with other well-known and highly regarded screening and diagnostic tools for various diseases/disorders, the classification accuracy of ID-CM was both absolutely and relatively strong....The simplicity and accuracy of ID-CM will enable health care professionals with or without training in neurology, pain, or headache to correctly identify the majority of patients with migraine or chronic migraine,” Dr. Lipton said. “Clinicians will then be able to accurately diagnose or refer affected patients to specialists for effective treatment that will reduce the burden of illness experienced by those with migraine and chronic migraine.”

—Erik Greb

A 12-item case-finding tool correctly classifies most people with migraine and chronic migraine, according to research published in the March issue of Cephalalgia. The tool, which is called Identify Chronic Migraine (ID-CM), classifies migraine with a sensitivity of 83.5% and a specificity of 88.5% and chronic migraine with a sensitivity of 80.6% and a specificity of 88.6%.

Migraine, and chronic migraine in particular, is underdiagnosed and undertreated, said Richard B. Lipton, MD, Vice Chair of Neurology at Albert Einstein College of Medicine in the Bronx, New York, and colleagues. The authors sought to develop a valid case-finding tool for chronic migraine that would be applicable to people who reported severe headache.

Richard B. Lipton, MD

The researchers developed their instrument in four stages. In the first stage, they convened an international panel of expert clinicians and researchers that selected potential items from existing diagnostic tools. The panel also suggested additional items for consideration. In stage two, Dr. Lipton and colleagues conducted cognitive debriefing interviews with people with chronic migraine to determine whether the latter understood the tool’s instructions and whether the items were worded properly.

Researchers also administered the items that had emerged from stage two, along with a set of patient-reported outcome measures, to a Web-based sample of 1,600 people with migraine or other severe headache. Data from this stage enabled them to perform a psychometric assessment of the new tool’s candidate items. Finally, in stage four, investigators compared diagnoses assigned using ID-CM with independent diagnoses assigned by headache experts using a semistructured diagnostic interview for migraine. Patients who had participated in the third stage of development were invited to participate in this stage.

The final version of ID-CM includes two questions about headache frequency, four about headache symptoms, two about medication use, two about whether headache interferes with activities, and two about whether headache interferes with making plans.

“ID-CM has been rigorously evaluated and has strong psychometric properties and high classification accuracy, both for migraine and chronic migraine,” said Dr. Lipton. “Compared with other well-known and highly regarded screening and diagnostic tools for various diseases/disorders, the classification accuracy of ID-CM was both absolutely and relatively strong....The simplicity and accuracy of ID-CM will enable health care professionals with or without training in neurology, pain, or headache to correctly identify the majority of patients with migraine or chronic migraine,” Dr. Lipton said. “Clinicians will then be able to accurately diagnose or refer affected patients to specialists for effective treatment that will reduce the burden of illness experienced by those with migraine and chronic migraine.”

—Erik Greb

STOWE, VERMONT—Rather than greater headache frequency, a systemic endocrine–metabolic disorder that is associated with frequent headaches may distinguish chronic migraine from episodic migraine, said Egilius L. H. Spierings, MD, PhD, at the 26th Annual Stowe Headache Symposium of the Headache Cooperative of New England.

Egilius L. H. Spierings, MD, PhD

According to the International Headache Society (IHS), a patient with headache on 15 or more days per month for more than three months, and whose headache has the features of migraine on at least eight days per month, fulfills the diagnostic criteria for chronic migraine. A migraineur with headache on 14 or fewer days per month has episodic migraine. The neurology community has accepted this distinction.

The IHS classification is “extremely simple” and “highly arbitrarily defined,” said Dr. Spierings, Director of the Headache and Face Pain Program at Tufts Medical Center in Boston and Clinical Professor of Craniofacial Pain at Tufts University. “There must be more behind that distinction, especially when you look at the question of why Botox works preventively in chronic migraine and not in episodic migraine.”

Taking the perspective of a general practitioner, rather than that of a headache specialist, may clarify the distinction between chronic and episodic migraine, according to Dr. Spierings. A general review of systems suggests that patients with episodic migraine tend to be healthy overall, while patients with chronic migraine tend to have many psychiatric and medical comorbidities. In an exploratory study, Dr. Spierings and colleagues found that women with chronic migraine had a significantly higher prevalence of menstrual cycle disorders (eg, oligomenorrhea and polymenorrhea) and dysmenorrhea, compared with women with episodic migraine.

These findings appear to be consistent with those of previous research. In 2002, Bigal and colleagues found that asthma, allergies, hypertension, and hypothyroidism were significantly more common in patients with chronic migraine than in those with episodic migraine. In 2006, Tietjen et al observed that endometriosis was significantly more common in women with chronic migraine than in women with episodic migraine.

In the most extensive study in this area, Ferrari et al found that psychiatric, gastrointestinal, musculoskeletal, ocular, genitourinary, hematologic, cerebrovascular, and cardiac comorbidities were significantly more common in patients with chronic migraine than in those with episodic migraine. Hypertension, constipation, and insomnia also were more prevalent in chronic migraine.

In addition, data from various studies show that patients with chronic migraine tend to be, on average, 10 to 20 years older than those with episodic migraine. About two-thirds of patients with chronic migraine develop their condition gradually over time out of episodic migraine, a transition that takes, on average, 11.6 years. During this period, these patients may develop the comorbidities that are more frequent in chronic migraine, said Dr. Spierings.

But younger patients with chronic migraine also have more comorbidities than patients of the same age with episodic migraine. One patient of Dr. Spierings was an 18-year-old woman who had had chronic migraine since menarche and whose mother had migraine. The woman’s comorbidities included fatigue, insomnia, anxiety, depression, tight and sore neck and shoulder muscles, reflux disease, and diarrhea. Another patient of Dr. Spierings was a 20-year-old woman who had had chronic migraine since menarche and whose mother had migraine. Among her comorbidities were fatigue, insomnia, depression, tight and sore neck and shoulder muscles, lumbago, polymenorrhea, dysmenorrhea, and hypermenorrhea.

Dr. Spierings also examined a 34-year-old woman without a family history of migraine. She developed a pressure sensation in the temples, but not headaches or migraine, after pregnancy. The woman’s comorbidities included fatigue, anxiety, tight and sore neck and shoulder muscles, fibromyalgia, gastritis, constipation, endometriosis, and hypermenorrhea.

All three patients have a disorder of multiple systems that affects the nervous system, the musculoskeletal system, the gastrointestinal system, and the genitourinary system. “The only unifying diagnosis … is somatic symptom disorder,” said Dr. Spierings. Yet this diagnosis is unsatisfying, he added.

“These people have a systemic endocrine–metabolic disorder centered around energy metabolism that causes the multitude of medical and psychiatric conditions that we tend to see in patients [with chronic migraine] .… It is a syndrome with multiple etiologies, either endocrine or metabolic, genetic or acquired.” The first two patients may have a “genetically determined headache amplifier” that contributed to the development of chronic migraine, Dr. Spierings added. The third patient, who has no family history of migraine, does not have this genetically determined headache amplifier.

In previous research, Dr. Spierings and colleagues concluded that stress, tension, irregular eating times, fatigue, and insufficient sleep were general headache triggers to which everyone is susceptible. “When we do not have that headache amplifier, we get regular headaches that we can combat with a couple of aspirin. When we have that headache amplifier inherited from one or both parents, we need specific antimigraine medications to take care of it,” he said. The inherited headache amplifier “is the essence of migraine” and is related to the threshold at which neurogenic inflammation occurs, said Dr. Spierings. Patients with chronic migraine have the headache amplifier and a systemic disorder not shared by patients with episodic migraine, he concluded.

—Erik Greb

STOWE, VERMONT—Rather than greater headache frequency, a systemic endocrine–metabolic disorder that is associated with frequent headaches may distinguish chronic migraine from episodic migraine, said Egilius L. H. Spierings, MD, PhD, at the 26th Annual Stowe Headache Symposium of the Headache Cooperative of New England.

Egilius L. H. Spierings, MD, PhD

According to the International Headache Society (IHS), a patient with headache on 15 or more days per month for more than three months, and whose headache has the features of migraine on at least eight days per month, fulfills the diagnostic criteria for chronic migraine. A migraineur with headache on 14 or fewer days per month has episodic migraine. The neurology community has accepted this distinction.

The IHS classification is “extremely simple” and “highly arbitrarily defined,” said Dr. Spierings, Director of the Headache and Face Pain Program at Tufts Medical Center in Boston and Clinical Professor of Craniofacial Pain at Tufts University. “There must be more behind that distinction, especially when you look at the question of why Botox works preventively in chronic migraine and not in episodic migraine.”

Taking the perspective of a general practitioner, rather than that of a headache specialist, may clarify the distinction between chronic and episodic migraine, according to Dr. Spierings. A general review of systems suggests that patients with episodic migraine tend to be healthy overall, while patients with chronic migraine tend to have many psychiatric and medical comorbidities. In an exploratory study, Dr. Spierings and colleagues found that women with chronic migraine had a significantly higher prevalence of menstrual cycle disorders (eg, oligomenorrhea and polymenorrhea) and dysmenorrhea, compared with women with episodic migraine.

These findings appear to be consistent with those of previous research. In 2002, Bigal and colleagues found that asthma, allergies, hypertension, and hypothyroidism were significantly more common in patients with chronic migraine than in those with episodic migraine. In 2006, Tietjen et al observed that endometriosis was significantly more common in women with chronic migraine than in women with episodic migraine.

In the most extensive study in this area, Ferrari et al found that psychiatric, gastrointestinal, musculoskeletal, ocular, genitourinary, hematologic, cerebrovascular, and cardiac comorbidities were significantly more common in patients with chronic migraine than in those with episodic migraine. Hypertension, constipation, and insomnia also were more prevalent in chronic migraine.

In addition, data from various studies show that patients with chronic migraine tend to be, on average, 10 to 20 years older than those with episodic migraine. About two-thirds of patients with chronic migraine develop their condition gradually over time out of episodic migraine, a transition that takes, on average, 11.6 years. During this period, these patients may develop the comorbidities that are more frequent in chronic migraine, said Dr. Spierings.

But younger patients with chronic migraine also have more comorbidities than patients of the same age with episodic migraine. One patient of Dr. Spierings was an 18-year-old woman who had had chronic migraine since menarche and whose mother had migraine. The woman’s comorbidities included fatigue, insomnia, anxiety, depression, tight and sore neck and shoulder muscles, reflux disease, and diarrhea. Another patient of Dr. Spierings was a 20-year-old woman who had had chronic migraine since menarche and whose mother had migraine. Among her comorbidities were fatigue, insomnia, depression, tight and sore neck and shoulder muscles, lumbago, polymenorrhea, dysmenorrhea, and hypermenorrhea.

Dr. Spierings also examined a 34-year-old woman without a family history of migraine. She developed a pressure sensation in the temples, but not headaches or migraine, after pregnancy. The woman’s comorbidities included fatigue, anxiety, tight and sore neck and shoulder muscles, fibromyalgia, gastritis, constipation, endometriosis, and hypermenorrhea.

All three patients have a disorder of multiple systems that affects the nervous system, the musculoskeletal system, the gastrointestinal system, and the genitourinary system. “The only unifying diagnosis … is somatic symptom disorder,” said Dr. Spierings. Yet this diagnosis is unsatisfying, he added.

“These people have a systemic endocrine–metabolic disorder centered around energy metabolism that causes the multitude of medical and psychiatric conditions that we tend to see in patients [with chronic migraine] .… It is a syndrome with multiple etiologies, either endocrine or metabolic, genetic or acquired.” The first two patients may have a “genetically determined headache amplifier” that contributed to the development of chronic migraine, Dr. Spierings added. The third patient, who has no family history of migraine, does not have this genetically determined headache amplifier.

In previous research, Dr. Spierings and colleagues concluded that stress, tension, irregular eating times, fatigue, and insufficient sleep were general headache triggers to which everyone is susceptible. “When we do not have that headache amplifier, we get regular headaches that we can combat with a couple of aspirin. When we have that headache amplifier inherited from one or both parents, we need specific antimigraine medications to take care of it,” he said. The inherited headache amplifier “is the essence of migraine” and is related to the threshold at which neurogenic inflammation occurs, said Dr. Spierings. Patients with chronic migraine have the headache amplifier and a systemic disorder not shared by patients with episodic migraine, he concluded.

—Erik Greb

STOWE, VERMONT—Rather than greater headache frequency, a systemic endocrine–metabolic disorder that is associated with frequent headaches may distinguish chronic migraine from episodic migraine, said Egilius L. H. Spierings, MD, PhD, at the 26th Annual Stowe Headache Symposium of the Headache Cooperative of New England.

Egilius L. H. Spierings, MD, PhD

According to the International Headache Society (IHS), a patient with headache on 15 or more days per month for more than three months, and whose headache has the features of migraine on at least eight days per month, fulfills the diagnostic criteria for chronic migraine. A migraineur with headache on 14 or fewer days per month has episodic migraine. The neurology community has accepted this distinction.

The IHS classification is “extremely simple” and “highly arbitrarily defined,” said Dr. Spierings, Director of the Headache and Face Pain Program at Tufts Medical Center in Boston and Clinical Professor of Craniofacial Pain at Tufts University. “There must be more behind that distinction, especially when you look at the question of why Botox works preventively in chronic migraine and not in episodic migraine.”

Taking the perspective of a general practitioner, rather than that of a headache specialist, may clarify the distinction between chronic and episodic migraine, according to Dr. Spierings. A general review of systems suggests that patients with episodic migraine tend to be healthy overall, while patients with chronic migraine tend to have many psychiatric and medical comorbidities. In an exploratory study, Dr. Spierings and colleagues found that women with chronic migraine had a significantly higher prevalence of menstrual cycle disorders (eg, oligomenorrhea and polymenorrhea) and dysmenorrhea, compared with women with episodic migraine.

These findings appear to be consistent with those of previous research. In 2002, Bigal and colleagues found that asthma, allergies, hypertension, and hypothyroidism were significantly more common in patients with chronic migraine than in those with episodic migraine. In 2006, Tietjen et al observed that endometriosis was significantly more common in women with chronic migraine than in women with episodic migraine.

In the most extensive study in this area, Ferrari et al found that psychiatric, gastrointestinal, musculoskeletal, ocular, genitourinary, hematologic, cerebrovascular, and cardiac comorbidities were significantly more common in patients with chronic migraine than in those with episodic migraine. Hypertension, constipation, and insomnia also were more prevalent in chronic migraine.

In addition, data from various studies show that patients with chronic migraine tend to be, on average, 10 to 20 years older than those with episodic migraine. About two-thirds of patients with chronic migraine develop their condition gradually over time out of episodic migraine, a transition that takes, on average, 11.6 years. During this period, these patients may develop the comorbidities that are more frequent in chronic migraine, said Dr. Spierings.

But younger patients with chronic migraine also have more comorbidities than patients of the same age with episodic migraine. One patient of Dr. Spierings was an 18-year-old woman who had had chronic migraine since menarche and whose mother had migraine. The woman’s comorbidities included fatigue, insomnia, anxiety, depression, tight and sore neck and shoulder muscles, reflux disease, and diarrhea. Another patient of Dr. Spierings was a 20-year-old woman who had had chronic migraine since menarche and whose mother had migraine. Among her comorbidities were fatigue, insomnia, depression, tight and sore neck and shoulder muscles, lumbago, polymenorrhea, dysmenorrhea, and hypermenorrhea.

Dr. Spierings also examined a 34-year-old woman without a family history of migraine. She developed a pressure sensation in the temples, but not headaches or migraine, after pregnancy. The woman’s comorbidities included fatigue, anxiety, tight and sore neck and shoulder muscles, fibromyalgia, gastritis, constipation, endometriosis, and hypermenorrhea.

All three patients have a disorder of multiple systems that affects the nervous system, the musculoskeletal system, the gastrointestinal system, and the genitourinary system. “The only unifying diagnosis … is somatic symptom disorder,” said Dr. Spierings. Yet this diagnosis is unsatisfying, he added.

“These people have a systemic endocrine–metabolic disorder centered around energy metabolism that causes the multitude of medical and psychiatric conditions that we tend to see in patients [with chronic migraine] .… It is a syndrome with multiple etiologies, either endocrine or metabolic, genetic or acquired.” The first two patients may have a “genetically determined headache amplifier” that contributed to the development of chronic migraine, Dr. Spierings added. The third patient, who has no family history of migraine, does not have this genetically determined headache amplifier.

In previous research, Dr. Spierings and colleagues concluded that stress, tension, irregular eating times, fatigue, and insufficient sleep were general headache triggers to which everyone is susceptible. “When we do not have that headache amplifier, we get regular headaches that we can combat with a couple of aspirin. When we have that headache amplifier inherited from one or both parents, we need specific antimigraine medications to take care of it,” he said. The inherited headache amplifier “is the essence of migraine” and is related to the threshold at which neurogenic inflammation occurs, said Dr. Spierings. Patients with chronic migraine have the headache amplifier and a systemic disorder not shared by patients with episodic migraine, he concluded.

—Erik Greb

In the age of technology, parents denying their teens a smartphone is blatant child abuse, at least in the eyes of the teen. Between Twitter, Instagram, and Snapchat, a teen’s entire life revolves around minute-to-minute check-ins. Smartphones have opened the door for sexual predators, bullying, and complete withdrawal from the world that surrounds them. But, with every bad there is a good and it’s knowing how to make the technology takeover work for you.

The smartphone is the best bargaining chip ever created. A teen would sooner die than lose his or her phone. Parents need to use this upper hand to get just about anything done: “You will get your phone back when XYZ is done.” Teens should understand that a phone is a privilege and not a right, so if they don’t want to cooperate, then there is a consequence.

Second, there is no greater source of information than a teen’s phone. From information in text, to locations, to the dreaded selfies, teens cannot help themselves when it comes to sharing every aspect of their lives. There are countless stories of teens getting busted because they posted a picture on Instagram with the person they were not supposed to be with or from a place they were not supposed to be. There are several great apps that allow parents to see deleted texts, and track locations and websites visited. These same apps allow parents to add controls that block X-rated websites, and notify them when the teen leaves a location or signs up for social media apps.

Accidents are the leading cause of death among teens and smartphones have only increased that. A recent study showed that 34% admitted to texting and driving. Another study reported that 11 teens die per day* because of distracted driver accidents. Not only are teens distracted, they also are inexperienced and are increasing their risk of injury. Teens are 23 times more likely to be in an accident as a result of distracted driving.

©ponsulak/ThinkStock.com

Now, there are apps that will alert parents when the teen is driving above the speed limit or has left the restricted area designated by the parent. These apps can silence incoming texts and prevent texts from being sent if the teen is in motion. Some of the apps will read the text out loud and respond with an automated response, letting the caller know that they are unavailable. Canary, My Mobile Watchdog, and Drivesafe.ly are examples, but both Sprint and Verizon have similar apps available. This is an excellent way for parents to monitor teen driving habits. The cost varies from $7.99/month to $99/month but the information provided is priceless.

Whether we like it or not, smartphones are here and have totally changed how teens interact and give them limitless exposure. Many parents, even if they own a smartphone, only use it for its basic functions and may have no idea these types of controls exist. Educating parents that they can use the phone as a tool to monitor and protect their teens is an important part of the well visit, and could very well save a life.

Dr. Pearce is a pediatrician in Frankfort, Ill. Email her at [email protected].

*Correction, 6/1/2016: The frequency of teen deaths due to distracted driver accidents was misquoted.

In the age of technology, parents denying their teens a smartphone is blatant child abuse, at least in the eyes of the teen. Between Twitter, Instagram, and Snapchat, a teen’s entire life revolves around minute-to-minute check-ins. Smartphones have opened the door for sexual predators, bullying, and complete withdrawal from the world that surrounds them. But, with every bad there is a good and it’s knowing how to make the technology takeover work for you.

The smartphone is the best bargaining chip ever created. A teen would sooner die than lose his or her phone. Parents need to use this upper hand to get just about anything done: “You will get your phone back when XYZ is done.” Teens should understand that a phone is a privilege and not a right, so if they don’t want to cooperate, then there is a consequence.

Second, there is no greater source of information than a teen’s phone. From information in text, to locations, to the dreaded selfies, teens cannot help themselves when it comes to sharing every aspect of their lives. There are countless stories of teens getting busted because they posted a picture on Instagram with the person they were not supposed to be with or from a place they were not supposed to be. There are several great apps that allow parents to see deleted texts, and track locations and websites visited. These same apps allow parents to add controls that block X-rated websites, and notify them when the teen leaves a location or signs up for social media apps.

Accidents are the leading cause of death among teens and smartphones have only increased that. A recent study showed that 34% admitted to texting and driving. Another study reported that 11 teens die per day* because of distracted driver accidents. Not only are teens distracted, they also are inexperienced and are increasing their risk of injury. Teens are 23 times more likely to be in an accident as a result of distracted driving.

©ponsulak/ThinkStock.com

Now, there are apps that will alert parents when the teen is driving above the speed limit or has left the restricted area designated by the parent. These apps can silence incoming texts and prevent texts from being sent if the teen is in motion. Some of the apps will read the text out loud and respond with an automated response, letting the caller know that they are unavailable. Canary, My Mobile Watchdog, and Drivesafe.ly are examples, but both Sprint and Verizon have similar apps available. This is an excellent way for parents to monitor teen driving habits. The cost varies from $7.99/month to $99/month but the information provided is priceless.

Whether we like it or not, smartphones are here and have totally changed how teens interact and give them limitless exposure. Many parents, even if they own a smartphone, only use it for its basic functions and may have no idea these types of controls exist. Educating parents that they can use the phone as a tool to monitor and protect their teens is an important part of the well visit, and could very well save a life.

Dr. Pearce is a pediatrician in Frankfort, Ill. Email her at [email protected].

*Correction, 6/1/2016: The frequency of teen deaths due to distracted driver accidents was misquoted.

In the age of technology, parents denying their teens a smartphone is blatant child abuse, at least in the eyes of the teen. Between Twitter, Instagram, and Snapchat, a teen’s entire life revolves around minute-to-minute check-ins. Smartphones have opened the door for sexual predators, bullying, and complete withdrawal from the world that surrounds them. But, with every bad there is a good and it’s knowing how to make the technology takeover work for you.

The smartphone is the best bargaining chip ever created. A teen would sooner die than lose his or her phone. Parents need to use this upper hand to get just about anything done: “You will get your phone back when XYZ is done.” Teens should understand that a phone is a privilege and not a right, so if they don’t want to cooperate, then there is a consequence.

Second, there is no greater source of information than a teen’s phone. From information in text, to locations, to the dreaded selfies, teens cannot help themselves when it comes to sharing every aspect of their lives. There are countless stories of teens getting busted because they posted a picture on Instagram with the person they were not supposed to be with or from a place they were not supposed to be. There are several great apps that allow parents to see deleted texts, and track locations and websites visited. These same apps allow parents to add controls that block X-rated websites, and notify them when the teen leaves a location or signs up for social media apps.

Accidents are the leading cause of death among teens and smartphones have only increased that. A recent study showed that 34% admitted to texting and driving. Another study reported that 11 teens die per day* because of distracted driver accidents. Not only are teens distracted, they also are inexperienced and are increasing their risk of injury. Teens are 23 times more likely to be in an accident as a result of distracted driving.

©ponsulak/ThinkStock.com

Now, there are apps that will alert parents when the teen is driving above the speed limit or has left the restricted area designated by the parent. These apps can silence incoming texts and prevent texts from being sent if the teen is in motion. Some of the apps will read the text out loud and respond with an automated response, letting the caller know that they are unavailable. Canary, My Mobile Watchdog, and Drivesafe.ly are examples, but both Sprint and Verizon have similar apps available. This is an excellent way for parents to monitor teen driving habits. The cost varies from $7.99/month to $99/month but the information provided is priceless.

Whether we like it or not, smartphones are here and have totally changed how teens interact and give them limitless exposure. Many parents, even if they own a smartphone, only use it for its basic functions and may have no idea these types of controls exist. Educating parents that they can use the phone as a tool to monitor and protect their teens is an important part of the well visit, and could very well save a life.

Dr. Pearce is a pediatrician in Frankfort, Ill. Email her at [email protected].

*Correction, 6/1/2016: The frequency of teen deaths due to distracted driver accidents was misquoted.

Treating multiple myeloma cells with panobinostat and FK506 reduced their viability by inhibiting expression of the PPP3CA catalytic subunit of calcineurin, according to researchers.

“The development of new calcineurin-targeted therapies, which inhibit PPP3CA–NF-kappaB signaling by small molecules, is expected to profoundly improve the treatment of multiple myeloma. This will overcome drug resistance and improve osteolytic lesions in a wide range of patients, including those receiving reduced intensity–conditioned allogeneic stem cell transplantation, who may be treated with panobinostat and FK506,” wrote Dr. Yoichi Imai of Tokyo Women’s Medical University in Japan, and his associates (JCI Insight 2016 doi: 10.1172/jci.insight.85061). .

Adding panobinostat to bortezomib and dexamethasone has been shown to improve progression-free survival in relapsed and refractory multiple myeloma, the researchers noted. Other studies have linked calcineurin activation to the pathogenesis of T-cell cancers, and calcineurin inhibition seems to be involved in defective B-cell activation, they added.

Eight candidate oncogenes were identified by use of the Gene Expression Omnibus. PPP3CA was expressed at significantly higher levels in multiple myeloma cells from patients with stage III disease compared with those with stage I disease (P = .016). Furthermore, levels of serum lactate dehydrogenase correlated with PPP3CA expression and with poor overall and progression-free survival. Patients with high PPP3CA expression also had high levels of alpha₄ integrins, which mediate resistance to bortezomib and conventional chemotherapy, the researchers noted.

When multiple myeloma cells were exposed to either panobinostat or a control agent, PPP3CA dropped in the panobinostat-treated cells. Adding the proteasome inhibitor lactacystin to the mixture counteracted this effect, “supporting the possibility that PPP3CA expression was reduced through protein degradation by panobinostat,” they said.

Levels of PPP3CA expression were lower in multiple myeloma cells that were cotreated with an HDAC inhibitor (panobinostat or ACY-1215) and the immunosuppressive agent FK506 than in multiple myeloma cells that were exposed only to an HDAC inhibitor. In addition, the combination regimen blocked the formation of osteoclasts, which are involved in osteolytic lesions, the researchers noted.

Also, significantly higher PPP3CA expression, which correlated with worse progression-free survival, was noted in bortezomib-resistant patients, compared with bortezomib-sensitive patients.

“The cytotoxic effect exerted by panobinostat on CD20+ cells was subtle, while the addition of FK506 did not increase their viability,” the researchers reported. “Moreover, development of T and B lineage cells was normal in PPP3CA-deficient mice, and panobinostat did not compromise donor lymphocyte reconstitution in a mouse BM transplantation model. These results suggest that calcineurin-targeting therapy exerts an antimyeloma effect without inducing significant side effects in normal lymphoid systems.”

The Japan Society for the Promotion of Science, the Takeda Science Foundation, the International Myeloma Foundation, and the Japan Leukemia Research Fund funded the study. The investigators had no disclosures.

Treating multiple myeloma cells with panobinostat and FK506 reduced their viability by inhibiting expression of the PPP3CA catalytic subunit of calcineurin, according to researchers.

“The development of new calcineurin-targeted therapies, which inhibit PPP3CA–NF-kappaB signaling by small molecules, is expected to profoundly improve the treatment of multiple myeloma. This will overcome drug resistance and improve osteolytic lesions in a wide range of patients, including those receiving reduced intensity–conditioned allogeneic stem cell transplantation, who may be treated with panobinostat and FK506,” wrote Dr. Yoichi Imai of Tokyo Women’s Medical University in Japan, and his associates (JCI Insight 2016 doi: 10.1172/jci.insight.85061). .

Adding panobinostat to bortezomib and dexamethasone has been shown to improve progression-free survival in relapsed and refractory multiple myeloma, the researchers noted. Other studies have linked calcineurin activation to the pathogenesis of T-cell cancers, and calcineurin inhibition seems to be involved in defective B-cell activation, they added.

Eight candidate oncogenes were identified by use of the Gene Expression Omnibus. PPP3CA was expressed at significantly higher levels in multiple myeloma cells from patients with stage III disease compared with those with stage I disease (P = .016). Furthermore, levels of serum lactate dehydrogenase correlated with PPP3CA expression and with poor overall and progression-free survival. Patients with high PPP3CA expression also had high levels of alpha₄ integrins, which mediate resistance to bortezomib and conventional chemotherapy, the researchers noted.

When multiple myeloma cells were exposed to either panobinostat or a control agent, PPP3CA dropped in the panobinostat-treated cells. Adding the proteasome inhibitor lactacystin to the mixture counteracted this effect, “supporting the possibility that PPP3CA expression was reduced through protein degradation by panobinostat,” they said.

Levels of PPP3CA expression were lower in multiple myeloma cells that were cotreated with an HDAC inhibitor (panobinostat or ACY-1215) and the immunosuppressive agent FK506 than in multiple myeloma cells that were exposed only to an HDAC inhibitor. In addition, the combination regimen blocked the formation of osteoclasts, which are involved in osteolytic lesions, the researchers noted.

Also, significantly higher PPP3CA expression, which correlated with worse progression-free survival, was noted in bortezomib-resistant patients, compared with bortezomib-sensitive patients.

“The cytotoxic effect exerted by panobinostat on CD20+ cells was subtle, while the addition of FK506 did not increase their viability,” the researchers reported. “Moreover, development of T and B lineage cells was normal in PPP3CA-deficient mice, and panobinostat did not compromise donor lymphocyte reconstitution in a mouse BM transplantation model. These results suggest that calcineurin-targeting therapy exerts an antimyeloma effect without inducing significant side effects in normal lymphoid systems.”

The Japan Society for the Promotion of Science, the Takeda Science Foundation, the International Myeloma Foundation, and the Japan Leukemia Research Fund funded the study. The investigators had no disclosures.

Treating multiple myeloma cells with panobinostat and FK506 reduced their viability by inhibiting expression of the PPP3CA catalytic subunit of calcineurin, according to researchers.

“The development of new calcineurin-targeted therapies, which inhibit PPP3CA–NF-kappaB signaling by small molecules, is expected to profoundly improve the treatment of multiple myeloma. This will overcome drug resistance and improve osteolytic lesions in a wide range of patients, including those receiving reduced intensity–conditioned allogeneic stem cell transplantation, who may be treated with panobinostat and FK506,” wrote Dr. Yoichi Imai of Tokyo Women’s Medical University in Japan, and his associates (JCI Insight 2016 doi: 10.1172/jci.insight.85061). .

Adding panobinostat to bortezomib and dexamethasone has been shown to improve progression-free survival in relapsed and refractory multiple myeloma, the researchers noted. Other studies have linked calcineurin activation to the pathogenesis of T-cell cancers, and calcineurin inhibition seems to be involved in defective B-cell activation, they added.

Eight candidate oncogenes were identified by use of the Gene Expression Omnibus. PPP3CA was expressed at significantly higher levels in multiple myeloma cells from patients with stage III disease compared with those with stage I disease (P = .016). Furthermore, levels of serum lactate dehydrogenase correlated with PPP3CA expression and with poor overall and progression-free survival. Patients with high PPP3CA expression also had high levels of alpha₄ integrins, which mediate resistance to bortezomib and conventional chemotherapy, the researchers noted.

When multiple myeloma cells were exposed to either panobinostat or a control agent, PPP3CA dropped in the panobinostat-treated cells. Adding the proteasome inhibitor lactacystin to the mixture counteracted this effect, “supporting the possibility that PPP3CA expression was reduced through protein degradation by panobinostat,” they said.

Levels of PPP3CA expression were lower in multiple myeloma cells that were cotreated with an HDAC inhibitor (panobinostat or ACY-1215) and the immunosuppressive agent FK506 than in multiple myeloma cells that were exposed only to an HDAC inhibitor. In addition, the combination regimen blocked the formation of osteoclasts, which are involved in osteolytic lesions, the researchers noted.

Also, significantly higher PPP3CA expression, which correlated with worse progression-free survival, was noted in bortezomib-resistant patients, compared with bortezomib-sensitive patients.

“The cytotoxic effect exerted by panobinostat on CD20+ cells was subtle, while the addition of FK506 did not increase their viability,” the researchers reported. “Moreover, development of T and B lineage cells was normal in PPP3CA-deficient mice, and panobinostat did not compromise donor lymphocyte reconstitution in a mouse BM transplantation model. These results suggest that calcineurin-targeting therapy exerts an antimyeloma effect without inducing significant side effects in normal lymphoid systems.”

The Japan Society for the Promotion of Science, the Takeda Science Foundation, the International Myeloma Foundation, and the Japan Leukemia Research Fund funded the study. The investigators had no disclosures.

CHICAGO – Just over one-half of all sudden deaths in a large pediatric case series were due to a primary arrhythmia syndrome, Dr. Grazia Delle Donne reported at the annual meeting of the American College of Cardiology.

She presented an analysis of all patients under the age of 18 years who were referred to London’s Royal Brompton Hospital for post mortem examination following presumed sudden cardiac death during 1991-2013. Royal Brompton is a national referral center for sudden cardiac death.

The review was undertaken because sudden cardiac death in the pediatric population occurs infrequently. Little is known about the prevalence of the various causes, noted Dr. Delle Donne of Royal Brompton.

Bruce Jancin/Frontline Medical News

Of the 398 subjects, 266 (67%) were female. The median age at death was 14 years. Twenty-two percent of the fatalities occurred during or immediately after exercise. Thirty-nine percent occurred while at rest.

Thirty-one percent of subjects had a family history of sudden cardiac death, another 14% had a family history of cardiomyopathy, and in 5% of cases there was a significant family history of arrhythmia.

Five percent of the children were known to have congenital heart disease. Eighteen percent of the children had a history of syncope.

Investigators determined that a primary arrhythmia syndrome such as long QT or Brugada syndrome was the cause of sudden death in 54% of cases. Death was attributed to cardiomyopathy in 15% cases, congenital heart disease in 8%, myocarditis in 6%, and coronary anomalies in 5%, with miscellaneous causes accounting for the remainder.

Dr. Delle Donne reported having no financial conflicts of interest regarding her presentation.

[email protected]

CHICAGO – Just over one-half of all sudden deaths in a large pediatric case series were due to a primary arrhythmia syndrome, Dr. Grazia Delle Donne reported at the annual meeting of the American College of Cardiology.

She presented an analysis of all patients under the age of 18 years who were referred to London’s Royal Brompton Hospital for post mortem examination following presumed sudden cardiac death during 1991-2013. Royal Brompton is a national referral center for sudden cardiac death.

The review was undertaken because sudden cardiac death in the pediatric population occurs infrequently. Little is known about the prevalence of the various causes, noted Dr. Delle Donne of Royal Brompton.

Bruce Jancin/Frontline Medical News

Of the 398 subjects, 266 (67%) were female. The median age at death was 14 years. Twenty-two percent of the fatalities occurred during or immediately after exercise. Thirty-nine percent occurred while at rest.

Thirty-one percent of subjects had a family history of sudden cardiac death, another 14% had a family history of cardiomyopathy, and in 5% of cases there was a significant family history of arrhythmia.

Five percent of the children were known to have congenital heart disease. Eighteen percent of the children had a history of syncope.

Investigators determined that a primary arrhythmia syndrome such as long QT or Brugada syndrome was the cause of sudden death in 54% of cases. Death was attributed to cardiomyopathy in 15% cases, congenital heart disease in 8%, myocarditis in 6%, and coronary anomalies in 5%, with miscellaneous causes accounting for the remainder.

Dr. Delle Donne reported having no financial conflicts of interest regarding her presentation.

[email protected]

CHICAGO – Just over one-half of all sudden deaths in a large pediatric case series were due to a primary arrhythmia syndrome, Dr. Grazia Delle Donne reported at the annual meeting of the American College of Cardiology.

She presented an analysis of all patients under the age of 18 years who were referred to London’s Royal Brompton Hospital for post mortem examination following presumed sudden cardiac death during 1991-2013. Royal Brompton is a national referral center for sudden cardiac death.

The review was undertaken because sudden cardiac death in the pediatric population occurs infrequently. Little is known about the prevalence of the various causes, noted Dr. Delle Donne of Royal Brompton.

Bruce Jancin/Frontline Medical News

Of the 398 subjects, 266 (67%) were female. The median age at death was 14 years. Twenty-two percent of the fatalities occurred during or immediately after exercise. Thirty-nine percent occurred while at rest.

Thirty-one percent of subjects had a family history of sudden cardiac death, another 14% had a family history of cardiomyopathy, and in 5% of cases there was a significant family history of arrhythmia.

Five percent of the children were known to have congenital heart disease. Eighteen percent of the children had a history of syncope.

Investigators determined that a primary arrhythmia syndrome such as long QT or Brugada syndrome was the cause of sudden death in 54% of cases. Death was attributed to cardiomyopathy in 15% cases, congenital heart disease in 8%, myocarditis in 6%, and coronary anomalies in 5%, with miscellaneous causes accounting for the remainder.

Dr. Delle Donne reported having no financial conflicts of interest regarding her presentation.

[email protected]

Supplement Editor:
M. Cecilia Lansang, MD, MPH

Contents

Diabetes management today: Issues in achieving glycemic goals
M. Cecilia Lansang

The role of hemoglobin A1c in the assessment of diabetes and cardiovascular risk
Courtney Nagel Sandler and Marie E. McDonnell

Antihyperglycemic drugs and cardiovascular outcomes in type 2 diabetes
Om P. Ganda

Newer oral and noninsulin therapies to treat type 2 diabetes mellitus
Kathie L. Hermayer and Andrew Dake

New insulin preparations: A primer for the clinician
Luigi Meneghini

Inpatient hyperglycemia management: A practical review for primary medical and surgical teams
M. Cecilia Lansang and Guillermo E. Umpierrez

Supplement Editor:
M. Cecilia Lansang, MD, MPH

Contents

Diabetes management today: Issues in achieving glycemic goals
M. Cecilia Lansang

The role of hemoglobin A1c in the assessment of diabetes and cardiovascular risk
Courtney Nagel Sandler and Marie E. McDonnell

Antihyperglycemic drugs and cardiovascular outcomes in type 2 diabetes
Om P. Ganda

Newer oral and noninsulin therapies to treat type 2 diabetes mellitus
Kathie L. Hermayer and Andrew Dake

New insulin preparations: A primer for the clinician
Luigi Meneghini

Inpatient hyperglycemia management: A practical review for primary medical and surgical teams
M. Cecilia Lansang and Guillermo E. Umpierrez

Supplement Editor:
M. Cecilia Lansang, MD, MPH

Contents

Diabetes management today: Issues in achieving glycemic goals
M. Cecilia Lansang

The role of hemoglobin A1c in the assessment of diabetes and cardiovascular risk
Courtney Nagel Sandler and Marie E. McDonnell

Antihyperglycemic drugs and cardiovascular outcomes in type 2 diabetes
Om P. Ganda

Newer oral and noninsulin therapies to treat type 2 diabetes mellitus
Kathie L. Hermayer and Andrew Dake

New insulin preparations: A primer for the clinician
Luigi Meneghini

Inpatient hyperglycemia management: A practical review for primary medical and surgical teams
M. Cecilia Lansang and Guillermo E. Umpierrez

Guest Editor
Andrew M. Kaunitz, MD

Authors
Sheryl Kingsberg, PhD; Michael Krychman, MD; Juliana M. Kling, MD, MPH; JoAnn E. Manson, MD, DrPH; James H. Liu, MD; Gretchen Collins, MD; Susan Kellogg Spadt, PhD, CRNP, IF, FCST, CSC

The object of this special issue is to enhance how you respond to and manage patients' menopausal and sexuality symptom concerns. The articles aim to alert women's health professionals to:

• the effects of sexual dysfunction, genitourinary syndrome of menopause in particular, on women emotionally and physically, and the available treatment options
• current nonhormonal treatment for hot flashes
• latest data on SERMs' role in managing menopausal symptoms, considering matching patients' symptoms to agents
• recommendations for intimacy counseling.

Articles included:

Image

Not enough women are receiving treatment for bothersome menopausal symptoms
Andrew M. Kaunitz, MD
Mitigating the impact of genitourinary syndrome of menopause on sexuality
Sheryl Kingsberg, PhD, and Michael Krychman, MD
Nonhormonal treatment options for vasomotor symptoms of menopause
Juliana M. Kling, MD, MPH, and JoAnn E. Manson, MD, DrPH
SERMs in menopause: Matching agents to patients' symptoms and attributes
James H. Liu, MD, and Gretchen Collins, MD

Tips for counseling women about intimacy after menopause
Susan Kellogg Spadt, PhD, CRNP, IF, FCST, CSC

Guest Editor
Andrew M. Kaunitz, MD

Authors
Sheryl Kingsberg, PhD; Michael Krychman, MD; Juliana M. Kling, MD, MPH; JoAnn E. Manson, MD, DrPH; James H. Liu, MD; Gretchen Collins, MD; Susan Kellogg Spadt, PhD, CRNP, IF, FCST, CSC

The object of this special issue is to enhance how you respond to and manage patients' menopausal and sexuality symptom concerns. The articles aim to alert women's health professionals to:

• the effects of sexual dysfunction, genitourinary syndrome of menopause in particular, on women emotionally and physically, and the available treatment options
• current nonhormonal treatment for hot flashes
• latest data on SERMs' role in managing menopausal symptoms, considering matching patients' symptoms to agents
• recommendations for intimacy counseling.

Articles included:

Image

Not enough women are receiving treatment for bothersome menopausal symptoms
Andrew M. Kaunitz, MD
Mitigating the impact of genitourinary syndrome of menopause on sexuality
Sheryl Kingsberg, PhD, and Michael Krychman, MD
Nonhormonal treatment options for vasomotor symptoms of menopause
Juliana M. Kling, MD, MPH, and JoAnn E. Manson, MD, DrPH
SERMs in menopause: Matching agents to patients' symptoms and attributes
James H. Liu, MD, and Gretchen Collins, MD

Tips for counseling women about intimacy after menopause
Susan Kellogg Spadt, PhD, CRNP, IF, FCST, CSC

Guest Editor
Andrew M. Kaunitz, MD

Authors
Sheryl Kingsberg, PhD; Michael Krychman, MD; Juliana M. Kling, MD, MPH; JoAnn E. Manson, MD, DrPH; James H. Liu, MD; Gretchen Collins, MD; Susan Kellogg Spadt, PhD, CRNP, IF, FCST, CSC

The object of this special issue is to enhance how you respond to and manage patients' menopausal and sexuality symptom concerns. The articles aim to alert women's health professionals to:

• the effects of sexual dysfunction, genitourinary syndrome of menopause in particular, on women emotionally and physically, and the available treatment options
• current nonhormonal treatment for hot flashes
• latest data on SERMs' role in managing menopausal symptoms, considering matching patients' symptoms to agents
• recommendations for intimacy counseling.

Articles included:

Image

Not enough women are receiving treatment for bothersome menopausal symptoms
Andrew M. Kaunitz, MD
Mitigating the impact of genitourinary syndrome of menopause on sexuality
Sheryl Kingsberg, PhD, and Michael Krychman, MD
Nonhormonal treatment options for vasomotor symptoms of menopause
Juliana M. Kling, MD, MPH, and JoAnn E. Manson, MD, DrPH
SERMs in menopause: Matching agents to patients' symptoms and attributes
James H. Liu, MD, and Gretchen Collins, MD

Tips for counseling women about intimacy after menopause
Susan Kellogg Spadt, PhD, CRNP, IF, FCST, CSC