Literature Review

Health care professionals and patients with epilepsy lack a common understanding of seizure clusters, according to research published in the April issue of Epilepsy & Behavior. Physicians and patients have differing ideas about the diagnosis, impact, and management of seizure clusters, and communication between these groups consequently is difficult. Investigators also cite a gap in the understanding of seizure clusters among health care providers as a group, and among patients as a group.

“An accepted, simple working definition of [seizure] clusters is needed that can be translated into consumer-friendly language,” said, Janice Buelow, RN, PhD, Associate Professor Emeritus at Indiana University School of Nursing in Annapolis, and colleagues. “This requires a common clinical lexicon to describe seizure clusters to facilitate communication among consumers, as well as between consumers and clinicians.” She defines consumers as including patients and caregivers.

Seizure clusters are not part of the International League Against Epilepsy Commission on Classification and Terminology, and neurologists have used inconsistent terminology to describe these events. Dr. Buelow and colleagues sought to describe and compare physicians’ and patients’ understanding of seizure clusters and to determine how these groups communicate about them. They reviewed websites with community forums such as those of the Epilepsy Foundation, Seizure Tracker, and Patients Like Me to describe patients’ understanding of seizure clusters. To describe clinicians’ understanding of seizure clusters, the investigators searched the literature for relevant articles.

Posts on community forums indicated that patients were confused about the meaning of a diagnosis of seizure clusters. Some patients thought that their physicians did not believe them when they reported having seizure clusters, which could reflect “a larger communication gap,” said Dr. Buelow. Patients also lacked confidence that physicians acknowledged their concerns about the events.

Clinicians viewed seizure clusters as a clinical event and discussed them in terms of frequency, duration, and appropriate treatment. In contrast, patients’ definitions focused on how seizure clusters affected their lives and showed little understanding of frequency.

The investigators observed that patients described seizure clusters as different from their usual seizures. Patients also remarked that a pattern of seizure clusters has a significant impact on their daily lives. Recurrent seizures contribute to a heightened sense of severity among patients, and misperceptions about the distinction between seizure clusters and status epilepticus can cause confusion, said the researchers.

The literature search revealed a lack of consensus among neurologists about what constitutes a seizure cluster. The literature also contained few discussions about risk factors, in contrast with community forums. Physicians’ discussions of severity focused on complications of seizure clusters such as status epilepticus or postictal psychosis. Professional discussions of the impact of seizure clusters mentioned progression to status epilepticus, emergency room visits, and hospital admissions rather than their influence on daily life. Neither patients nor physicians discussed how the groups communicate about seizure clusters.

—Erik Greb

Health care professionals and patients with epilepsy lack a common understanding of seizure clusters, according to research published in the April issue of Epilepsy & Behavior. Physicians and patients have differing ideas about the diagnosis, impact, and management of seizure clusters, and communication between these groups consequently is difficult. Investigators also cite a gap in the understanding of seizure clusters among health care providers as a group, and among patients as a group.

“An accepted, simple working definition of [seizure] clusters is needed that can be translated into consumer-friendly language,” said, Janice Buelow, RN, PhD, Associate Professor Emeritus at Indiana University School of Nursing in Annapolis, and colleagues. “This requires a common clinical lexicon to describe seizure clusters to facilitate communication among consumers, as well as between consumers and clinicians.” She defines consumers as including patients and caregivers.

Seizure clusters are not part of the International League Against Epilepsy Commission on Classification and Terminology, and neurologists have used inconsistent terminology to describe these events. Dr. Buelow and colleagues sought to describe and compare physicians’ and patients’ understanding of seizure clusters and to determine how these groups communicate about them. They reviewed websites with community forums such as those of the Epilepsy Foundation, Seizure Tracker, and Patients Like Me to describe patients’ understanding of seizure clusters. To describe clinicians’ understanding of seizure clusters, the investigators searched the literature for relevant articles.

Posts on community forums indicated that patients were confused about the meaning of a diagnosis of seizure clusters. Some patients thought that their physicians did not believe them when they reported having seizure clusters, which could reflect “a larger communication gap,” said Dr. Buelow. Patients also lacked confidence that physicians acknowledged their concerns about the events.

Clinicians viewed seizure clusters as a clinical event and discussed them in terms of frequency, duration, and appropriate treatment. In contrast, patients’ definitions focused on how seizure clusters affected their lives and showed little understanding of frequency.

The investigators observed that patients described seizure clusters as different from their usual seizures. Patients also remarked that a pattern of seizure clusters has a significant impact on their daily lives. Recurrent seizures contribute to a heightened sense of severity among patients, and misperceptions about the distinction between seizure clusters and status epilepticus can cause confusion, said the researchers.

The literature search revealed a lack of consensus among neurologists about what constitutes a seizure cluster. The literature also contained few discussions about risk factors, in contrast with community forums. Physicians’ discussions of severity focused on complications of seizure clusters such as status epilepticus or postictal psychosis. Professional discussions of the impact of seizure clusters mentioned progression to status epilepticus, emergency room visits, and hospital admissions rather than their influence on daily life. Neither patients nor physicians discussed how the groups communicate about seizure clusters.

—Erik Greb

Health care professionals and patients with epilepsy lack a common understanding of seizure clusters, according to research published in the April issue of Epilepsy & Behavior. Physicians and patients have differing ideas about the diagnosis, impact, and management of seizure clusters, and communication between these groups consequently is difficult. Investigators also cite a gap in the understanding of seizure clusters among health care providers as a group, and among patients as a group.

“An accepted, simple working definition of [seizure] clusters is needed that can be translated into consumer-friendly language,” said, Janice Buelow, RN, PhD, Associate Professor Emeritus at Indiana University School of Nursing in Annapolis, and colleagues. “This requires a common clinical lexicon to describe seizure clusters to facilitate communication among consumers, as well as between consumers and clinicians.” She defines consumers as including patients and caregivers.

Seizure clusters are not part of the International League Against Epilepsy Commission on Classification and Terminology, and neurologists have used inconsistent terminology to describe these events. Dr. Buelow and colleagues sought to describe and compare physicians’ and patients’ understanding of seizure clusters and to determine how these groups communicate about them. They reviewed websites with community forums such as those of the Epilepsy Foundation, Seizure Tracker, and Patients Like Me to describe patients’ understanding of seizure clusters. To describe clinicians’ understanding of seizure clusters, the investigators searched the literature for relevant articles.

Posts on community forums indicated that patients were confused about the meaning of a diagnosis of seizure clusters. Some patients thought that their physicians did not believe them when they reported having seizure clusters, which could reflect “a larger communication gap,” said Dr. Buelow. Patients also lacked confidence that physicians acknowledged their concerns about the events.

Clinicians viewed seizure clusters as a clinical event and discussed them in terms of frequency, duration, and appropriate treatment. In contrast, patients’ definitions focused on how seizure clusters affected their lives and showed little understanding of frequency.

The investigators observed that patients described seizure clusters as different from their usual seizures. Patients also remarked that a pattern of seizure clusters has a significant impact on their daily lives. Recurrent seizures contribute to a heightened sense of severity among patients, and misperceptions about the distinction between seizure clusters and status epilepticus can cause confusion, said the researchers.

The literature search revealed a lack of consensus among neurologists about what constitutes a seizure cluster. The literature also contained few discussions about risk factors, in contrast with community forums. Physicians’ discussions of severity focused on complications of seizure clusters such as status epilepticus or postictal psychosis. Professional discussions of the impact of seizure clusters mentioned progression to status epilepticus, emergency room visits, and hospital admissions rather than their influence on daily life. Neither patients nor physicians discussed how the groups communicate about seizure clusters.

—Erik Greb

Clinical question: What is the role for inpatient polysomnograms for children with medical complexity?

Background: Sleep-disordered breathing is more common in certain pediatric populations. Children with neuromuscular disease, craniofacial or tracheobronchial malformations, or developmental delay have up to 10 times the rate of sleep-disordered breathing as compared to the general pediatric population, with a prevalence as high as 40%. It is recommended that patients with neuromuscular conditions get annual polysomnograms (PSGs). The medical complexity and requirement for nursing and respiratory care makes it challenging to obtain routine outpatient PSGs in this population. This study is the first of its kind to examine the characteristics of patients receiving inpatient PSGs and to determine the effects the findings of these studies had on the patients’ care.

Study design: Retrospective case series.

Setting: Single, large, academic medical center.

Synopsis: Eight-five PSGs were completed on 70 patients during the study period. These occurred primarily in the pediatric intensive care unit (50 patients) but also in the neonatal intensive care unit (five patients) and the general pediatric floor (15 patients). The mean age of patients was 6.5 years, and 60% were male.

The most common diagnoses in this group were airway obstruction due to craniofacial abnormalities or defects of the tracheobronchial tree (54%), chronic respiratory failure (34%), hypoxic ischemic encephalopathy (23%), and genetic syndromes (14%). All sleep studies were successfully completed using the center’s dedicated sleep technicians and PSG scoring staff. There were no complications associated with the PSGs.

The most common specific indications for obtaining the PSGs were chronic pulmonary failure with airway obstruction and ventilator requirement assessment. Eighty-nine percent of patients had some abnormality of their PSG. Obstructive sleep apnea, tachypnea and desaturation, and disorders of sleep architecture were the most commonly found abnormalities.

The most common interventions based upon the PSG results were adjustment of ventilator parameters (46%), ENT referral for upper airway assessment (31%), and initiation of positive pressure ventilation (CPAP or BiPAP, 25%). Follow-up PSGs after these interventions demonstrated statistically significant improvement in apnea-hypopnea index, arousal index, and lowest oxygen saturation.

Bottom line: Inpatient PSGs for children with medical complexity are safe and often have significant findings that alter care for the patient.

Citation: Tkachenko N, Singh K, Abreu N, et al. Establishing a role for polysomnography in hospitalized children. Pediatr Neurol. 2016;57:39-45.e1. doi:10.1016/j.pediatrneurol.2015.12.020.

Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. Dupont Hospital for Children in Wilmington, Del., and assistant professor of pediatrics at Thomas Jefferson Medical College in Philadelphia.

Clinical question: What is the role for inpatient polysomnograms for children with medical complexity?

Background: Sleep-disordered breathing is more common in certain pediatric populations. Children with neuromuscular disease, craniofacial or tracheobronchial malformations, or developmental delay have up to 10 times the rate of sleep-disordered breathing as compared to the general pediatric population, with a prevalence as high as 40%. It is recommended that patients with neuromuscular conditions get annual polysomnograms (PSGs). The medical complexity and requirement for nursing and respiratory care makes it challenging to obtain routine outpatient PSGs in this population. This study is the first of its kind to examine the characteristics of patients receiving inpatient PSGs and to determine the effects the findings of these studies had on the patients’ care.

Study design: Retrospective case series.

Setting: Single, large, academic medical center.

Synopsis: Eight-five PSGs were completed on 70 patients during the study period. These occurred primarily in the pediatric intensive care unit (50 patients) but also in the neonatal intensive care unit (five patients) and the general pediatric floor (15 patients). The mean age of patients was 6.5 years, and 60% were male.

The most common diagnoses in this group were airway obstruction due to craniofacial abnormalities or defects of the tracheobronchial tree (54%), chronic respiratory failure (34%), hypoxic ischemic encephalopathy (23%), and genetic syndromes (14%). All sleep studies were successfully completed using the center’s dedicated sleep technicians and PSG scoring staff. There were no complications associated with the PSGs.

The most common specific indications for obtaining the PSGs were chronic pulmonary failure with airway obstruction and ventilator requirement assessment. Eighty-nine percent of patients had some abnormality of their PSG. Obstructive sleep apnea, tachypnea and desaturation, and disorders of sleep architecture were the most commonly found abnormalities.

The most common interventions based upon the PSG results were adjustment of ventilator parameters (46%), ENT referral for upper airway assessment (31%), and initiation of positive pressure ventilation (CPAP or BiPAP, 25%). Follow-up PSGs after these interventions demonstrated statistically significant improvement in apnea-hypopnea index, arousal index, and lowest oxygen saturation.

Bottom line: Inpatient PSGs for children with medical complexity are safe and often have significant findings that alter care for the patient.

Citation: Tkachenko N, Singh K, Abreu N, et al. Establishing a role for polysomnography in hospitalized children. Pediatr Neurol. 2016;57:39-45.e1. doi:10.1016/j.pediatrneurol.2015.12.020.

Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. Dupont Hospital for Children in Wilmington, Del., and assistant professor of pediatrics at Thomas Jefferson Medical College in Philadelphia.

Clinical question: What is the role for inpatient polysomnograms for children with medical complexity?

Background: Sleep-disordered breathing is more common in certain pediatric populations. Children with neuromuscular disease, craniofacial or tracheobronchial malformations, or developmental delay have up to 10 times the rate of sleep-disordered breathing as compared to the general pediatric population, with a prevalence as high as 40%. It is recommended that patients with neuromuscular conditions get annual polysomnograms (PSGs). The medical complexity and requirement for nursing and respiratory care makes it challenging to obtain routine outpatient PSGs in this population. This study is the first of its kind to examine the characteristics of patients receiving inpatient PSGs and to determine the effects the findings of these studies had on the patients’ care.

Study design: Retrospective case series.

Setting: Single, large, academic medical center.

Synopsis: Eight-five PSGs were completed on 70 patients during the study period. These occurred primarily in the pediatric intensive care unit (50 patients) but also in the neonatal intensive care unit (five patients) and the general pediatric floor (15 patients). The mean age of patients was 6.5 years, and 60% were male.

The most common diagnoses in this group were airway obstruction due to craniofacial abnormalities or defects of the tracheobronchial tree (54%), chronic respiratory failure (34%), hypoxic ischemic encephalopathy (23%), and genetic syndromes (14%). All sleep studies were successfully completed using the center’s dedicated sleep technicians and PSG scoring staff. There were no complications associated with the PSGs.

The most common specific indications for obtaining the PSGs were chronic pulmonary failure with airway obstruction and ventilator requirement assessment. Eighty-nine percent of patients had some abnormality of their PSG. Obstructive sleep apnea, tachypnea and desaturation, and disorders of sleep architecture were the most commonly found abnormalities.

The most common interventions based upon the PSG results were adjustment of ventilator parameters (46%), ENT referral for upper airway assessment (31%), and initiation of positive pressure ventilation (CPAP or BiPAP, 25%). Follow-up PSGs after these interventions demonstrated statistically significant improvement in apnea-hypopnea index, arousal index, and lowest oxygen saturation.

Bottom line: Inpatient PSGs for children with medical complexity are safe and often have significant findings that alter care for the patient.

Citation: Tkachenko N, Singh K, Abreu N, et al. Establishing a role for polysomnography in hospitalized children. Pediatr Neurol. 2016;57:39-45.e1. doi:10.1016/j.pediatrneurol.2015.12.020.

Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. Dupont Hospital for Children in Wilmington, Del., and assistant professor of pediatrics at Thomas Jefferson Medical College in Philadelphia.

Rosacea is an independent risk factor for Parkinson’s disease, according to data published online ahead of print March 21 in JAMA Neurology. Shared pathogenic mechanisms involving elevated matrix metalloproteinase activity could explain the association, but its clinical consequences require further study, according to the authors.

In a 2001 study of 70 patients with Parkinson’s disease, researchers observed that 18.6% of the population had rosacea and that 31.4% of participants had facial flushing associated with temperature changes. This study prompted Alexander Egeberg, MD, PhD, of the Department of Dermato-Allergology at the University of Copenhagen’s Herlev and Gentofte Hospital, and colleagues to evaluate a potential association between rosacea and Parkinson’s disease in a nationwide cohort of the Danish population.

The investigators included in the study all Danish citizens who were age 18 or older from January 1, 1997, to December 31, 2011. Patients with prevalent rosacea or Parkinson’s disease at baseline, as well as those with a history of antiparkinson dopaminergic drug use, were excluded. The investigators identified patients with rosacea by the first documentation of a hospital diagnosis of rosacea or the filling of a second prescription of topical metronidazole. The study’s primary end point was a hospital diagnosis of idiopathic Parkinson’s disease. The secondary end point was the initiation of treatment with antiparkinson dopaminergic agents.

The study’s final cohort included 5,472,745 people with a maximum follow-up of 15 years. In all, 68,053 people had rosacea, and the investigators designated the group of participants without rosacea as the reference population. In all, 22,387 people (43.8% women; mean age, 75.9) received a diagnosis of Parkinson’s disease during the study period. In addition, 93,411 people in the reference population and 1,169 people with rosacea initiated treatment with antiparkinson dopaminergic agents.

The incidence rates of Parkinson’s disease per 10,000 person-years were 3.54 in the reference population and 7.62 in patients with rosacea. The incidence rates of treatment with antiparkinson dopaminergic agents were 15.03 and 32.17, respectively. Parkinson’s disease occurred approximately 2.4 years earlier in patients with rosacea. The incidence rate ratio of Parkinson’s disease, adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, comorbidity, and medication, was 1.71 in patients with rosacea, compared with the reference population. The adjusted incidence rate ratio of treatment with antiparkinson dopaminergic agents was 1.59 in patients with rosacea, compared with the reference population.

Dr. Egeberg and colleagues found a reduced risk of Parkinson’s disease among patients who had filled prescriptions for a tetracycline. This finding suggests a need for randomized trials of this drug class in patients with Parkinson’s disease, they said.

In mouse models of Parkinson’s disease, increased expression of MMP-3 and MMP-9 has been implicated in the loss of dopaminergic neurons and nigrostriatal pathway degeneration. “Patients with rosacea also have increased activity of MMP-1, MMP-3, and MMP-9 in affected skin regions,” said the authors. “The recognition of neurogenic rosacea … lends further support to a pathogenic link between the two diseases. However, we emphasize that these findings are hypothesis generating; the basis for the pathogenic link between rosacea and Parkinson’s disease is unknown.”

—Erik Greb

Rosacea is an independent risk factor for Parkinson’s disease, according to data published online ahead of print March 21 in JAMA Neurology. Shared pathogenic mechanisms involving elevated matrix metalloproteinase activity could explain the association, but its clinical consequences require further study, according to the authors.

In a 2001 study of 70 patients with Parkinson’s disease, researchers observed that 18.6% of the population had rosacea and that 31.4% of participants had facial flushing associated with temperature changes. This study prompted Alexander Egeberg, MD, PhD, of the Department of Dermato-Allergology at the University of Copenhagen’s Herlev and Gentofte Hospital, and colleagues to evaluate a potential association between rosacea and Parkinson’s disease in a nationwide cohort of the Danish population.

The investigators included in the study all Danish citizens who were age 18 or older from January 1, 1997, to December 31, 2011. Patients with prevalent rosacea or Parkinson’s disease at baseline, as well as those with a history of antiparkinson dopaminergic drug use, were excluded. The investigators identified patients with rosacea by the first documentation of a hospital diagnosis of rosacea or the filling of a second prescription of topical metronidazole. The study’s primary end point was a hospital diagnosis of idiopathic Parkinson’s disease. The secondary end point was the initiation of treatment with antiparkinson dopaminergic agents.

The study’s final cohort included 5,472,745 people with a maximum follow-up of 15 years. In all, 68,053 people had rosacea, and the investigators designated the group of participants without rosacea as the reference population. In all, 22,387 people (43.8% women; mean age, 75.9) received a diagnosis of Parkinson’s disease during the study period. In addition, 93,411 people in the reference population and 1,169 people with rosacea initiated treatment with antiparkinson dopaminergic agents.

The incidence rates of Parkinson’s disease per 10,000 person-years were 3.54 in the reference population and 7.62 in patients with rosacea. The incidence rates of treatment with antiparkinson dopaminergic agents were 15.03 and 32.17, respectively. Parkinson’s disease occurred approximately 2.4 years earlier in patients with rosacea. The incidence rate ratio of Parkinson’s disease, adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, comorbidity, and medication, was 1.71 in patients with rosacea, compared with the reference population. The adjusted incidence rate ratio of treatment with antiparkinson dopaminergic agents was 1.59 in patients with rosacea, compared with the reference population.

Dr. Egeberg and colleagues found a reduced risk of Parkinson’s disease among patients who had filled prescriptions for a tetracycline. This finding suggests a need for randomized trials of this drug class in patients with Parkinson’s disease, they said.

In mouse models of Parkinson’s disease, increased expression of MMP-3 and MMP-9 has been implicated in the loss of dopaminergic neurons and nigrostriatal pathway degeneration. “Patients with rosacea also have increased activity of MMP-1, MMP-3, and MMP-9 in affected skin regions,” said the authors. “The recognition of neurogenic rosacea … lends further support to a pathogenic link between the two diseases. However, we emphasize that these findings are hypothesis generating; the basis for the pathogenic link between rosacea and Parkinson’s disease is unknown.”

—Erik Greb

Rosacea is an independent risk factor for Parkinson’s disease, according to data published online ahead of print March 21 in JAMA Neurology. Shared pathogenic mechanisms involving elevated matrix metalloproteinase activity could explain the association, but its clinical consequences require further study, according to the authors.

In a 2001 study of 70 patients with Parkinson’s disease, researchers observed that 18.6% of the population had rosacea and that 31.4% of participants had facial flushing associated with temperature changes. This study prompted Alexander Egeberg, MD, PhD, of the Department of Dermato-Allergology at the University of Copenhagen’s Herlev and Gentofte Hospital, and colleagues to evaluate a potential association between rosacea and Parkinson’s disease in a nationwide cohort of the Danish population.

The investigators included in the study all Danish citizens who were age 18 or older from January 1, 1997, to December 31, 2011. Patients with prevalent rosacea or Parkinson’s disease at baseline, as well as those with a history of antiparkinson dopaminergic drug use, were excluded. The investigators identified patients with rosacea by the first documentation of a hospital diagnosis of rosacea or the filling of a second prescription of topical metronidazole. The study’s primary end point was a hospital diagnosis of idiopathic Parkinson’s disease. The secondary end point was the initiation of treatment with antiparkinson dopaminergic agents.

The study’s final cohort included 5,472,745 people with a maximum follow-up of 15 years. In all, 68,053 people had rosacea, and the investigators designated the group of participants without rosacea as the reference population. In all, 22,387 people (43.8% women; mean age, 75.9) received a diagnosis of Parkinson’s disease during the study period. In addition, 93,411 people in the reference population and 1,169 people with rosacea initiated treatment with antiparkinson dopaminergic agents.

The incidence rates of Parkinson’s disease per 10,000 person-years were 3.54 in the reference population and 7.62 in patients with rosacea. The incidence rates of treatment with antiparkinson dopaminergic agents were 15.03 and 32.17, respectively. Parkinson’s disease occurred approximately 2.4 years earlier in patients with rosacea. The incidence rate ratio of Parkinson’s disease, adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, comorbidity, and medication, was 1.71 in patients with rosacea, compared with the reference population. The adjusted incidence rate ratio of treatment with antiparkinson dopaminergic agents was 1.59 in patients with rosacea, compared with the reference population.

Dr. Egeberg and colleagues found a reduced risk of Parkinson’s disease among patients who had filled prescriptions for a tetracycline. This finding suggests a need for randomized trials of this drug class in patients with Parkinson’s disease, they said.

In mouse models of Parkinson’s disease, increased expression of MMP-3 and MMP-9 has been implicated in the loss of dopaminergic neurons and nigrostriatal pathway degeneration. “Patients with rosacea also have increased activity of MMP-1, MMP-3, and MMP-9 in affected skin regions,” said the authors. “The recognition of neurogenic rosacea … lends further support to a pathogenic link between the two diseases. However, we emphasize that these findings are hypothesis generating; the basis for the pathogenic link between rosacea and Parkinson’s disease is unknown.”

—Erik Greb

Data from the mPower study of adults with Parkinson’s disease were published online March 3 in Scientific Data. A total of 9,520 participants, including patients and controls, consented to the observational study and agreed to share their data broadly with the research community. Participants downloaded an iPhone app that recorded data about their symptoms. The first six months of data from these participants were published.

“Our hope is that by sharing these data immediately, prior even to our own complete analysis, we will shorten the time to harnessing any utility that this study’s data may hold to improve the condition of patients who suffer from this disease,” said John Wilbanks and Stephen H. Friend, MD, PhD, both of Sage Bionetworks, in a commentary published in Nature Biotechnology.

Stephen H. Friend, MD, PhD

Sage Bionetworks initiated mPower in March 2015 to evaluate the feasibility of remotely collecting information about daily changes in symptom severity and their sensitivity to medication in Parkinson’s disease. Upon enrollment, participants were able to complete seven study tasks at any time. The first task was a baseline survey. Memory, tapping, voice, and walking tasks were to be completed three times per day. Participants also were asked to respond monthly to the Parkinson’s Disease Questionnaire-8 and a subset of questions from the Unified Parkinson’s Disease Rating Scale.

The memory, tapping, voice, and walking tasks were intended to be performed immediately before the patient took medication, after the patient took medication, and at another time. In the memory activity, patients watched a random series of squares in a grid light up one by one before being asked to touch the same squares in the correct order. In the tapping task, patients used two fingers to tap two stationary points on the screen for 20 seconds. During the voice activity, patients said, “Ah,” into a microphone at a steady volume for 10 seconds. In the walking activity, patients walked 20 steps in a straight line, turned around, and stood still for 30 seconds.

In all, 8,320 participants completed at least one survey or task after joining the study. A total of 6,805 participants completed the enrollment survey, and 1,087 of them reported having received a professional diagnosis of Parkinson’s disease. Follow-up was not consistent among participants, and 898 people contributed data on at least five days during the study’s first six months. The number of days that participants contributed data was similar between people with self-reported diagnosis of Parkinson’s disease and controls.

The mPower data may help establish the baseline variability of real-world activity measurement collected with mobile phones, and may help quantify fluctuation in the symptoms of Parkinson’s disease, said the authors.

—Erik Greb

Data from the mPower study of adults with Parkinson’s disease were published online March 3 in Scientific Data. A total of 9,520 participants, including patients and controls, consented to the observational study and agreed to share their data broadly with the research community. Participants downloaded an iPhone app that recorded data about their symptoms. The first six months of data from these participants were published.

“Our hope is that by sharing these data immediately, prior even to our own complete analysis, we will shorten the time to harnessing any utility that this study’s data may hold to improve the condition of patients who suffer from this disease,” said John Wilbanks and Stephen H. Friend, MD, PhD, both of Sage Bionetworks, in a commentary published in Nature Biotechnology.

Stephen H. Friend, MD, PhD

Sage Bionetworks initiated mPower in March 2015 to evaluate the feasibility of remotely collecting information about daily changes in symptom severity and their sensitivity to medication in Parkinson’s disease. Upon enrollment, participants were able to complete seven study tasks at any time. The first task was a baseline survey. Memory, tapping, voice, and walking tasks were to be completed three times per day. Participants also were asked to respond monthly to the Parkinson’s Disease Questionnaire-8 and a subset of questions from the Unified Parkinson’s Disease Rating Scale.

The memory, tapping, voice, and walking tasks were intended to be performed immediately before the patient took medication, after the patient took medication, and at another time. In the memory activity, patients watched a random series of squares in a grid light up one by one before being asked to touch the same squares in the correct order. In the tapping task, patients used two fingers to tap two stationary points on the screen for 20 seconds. During the voice activity, patients said, “Ah,” into a microphone at a steady volume for 10 seconds. In the walking activity, patients walked 20 steps in a straight line, turned around, and stood still for 30 seconds.

In all, 8,320 participants completed at least one survey or task after joining the study. A total of 6,805 participants completed the enrollment survey, and 1,087 of them reported having received a professional diagnosis of Parkinson’s disease. Follow-up was not consistent among participants, and 898 people contributed data on at least five days during the study’s first six months. The number of days that participants contributed data was similar between people with self-reported diagnosis of Parkinson’s disease and controls.

The mPower data may help establish the baseline variability of real-world activity measurement collected with mobile phones, and may help quantify fluctuation in the symptoms of Parkinson’s disease, said the authors.

—Erik Greb

Data from the mPower study of adults with Parkinson’s disease were published online March 3 in Scientific Data. A total of 9,520 participants, including patients and controls, consented to the observational study and agreed to share their data broadly with the research community. Participants downloaded an iPhone app that recorded data about their symptoms. The first six months of data from these participants were published.

“Our hope is that by sharing these data immediately, prior even to our own complete analysis, we will shorten the time to harnessing any utility that this study’s data may hold to improve the condition of patients who suffer from this disease,” said John Wilbanks and Stephen H. Friend, MD, PhD, both of Sage Bionetworks, in a commentary published in Nature Biotechnology.

Stephen H. Friend, MD, PhD

Sage Bionetworks initiated mPower in March 2015 to evaluate the feasibility of remotely collecting information about daily changes in symptom severity and their sensitivity to medication in Parkinson’s disease. Upon enrollment, participants were able to complete seven study tasks at any time. The first task was a baseline survey. Memory, tapping, voice, and walking tasks were to be completed three times per day. Participants also were asked to respond monthly to the Parkinson’s Disease Questionnaire-8 and a subset of questions from the Unified Parkinson’s Disease Rating Scale.

The memory, tapping, voice, and walking tasks were intended to be performed immediately before the patient took medication, after the patient took medication, and at another time. In the memory activity, patients watched a random series of squares in a grid light up one by one before being asked to touch the same squares in the correct order. In the tapping task, patients used two fingers to tap two stationary points on the screen for 20 seconds. During the voice activity, patients said, “Ah,” into a microphone at a steady volume for 10 seconds. In the walking activity, patients walked 20 steps in a straight line, turned around, and stood still for 30 seconds.

In all, 8,320 participants completed at least one survey or task after joining the study. A total of 6,805 participants completed the enrollment survey, and 1,087 of them reported having received a professional diagnosis of Parkinson’s disease. Follow-up was not consistent among participants, and 898 people contributed data on at least five days during the study’s first six months. The number of days that participants contributed data was similar between people with self-reported diagnosis of Parkinson’s disease and controls.

The mPower data may help establish the baseline variability of real-world activity measurement collected with mobile phones, and may help quantify fluctuation in the symptoms of Parkinson’s disease, said the authors.

—Erik Greb

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