Literature Review

Self-management of epilepsy using a group-format, remote intervention improves mood, quality of life, and health functioning in high-risk individuals, according to a randomized, controlled trial published in the September issue of Epilepsia.

In the six-month trial, 120 individuals with epilepsy who had experienced at least one epilepsy-related negative health event in the previous six months were randomized to a wait-list control group or a novel self‐management intervention.

The eight-session intervention, known as SMART, focused on modifiable factors that can be addressed with self-management, such as stress, substance abuse, routine, nutrition, and social support. It was delivered remotely during eight to 10 weeks, either by telephone or online, after an initial in-person session.

“SMART combines the portability and low cost of a Web‐based intervention with the personally salient components of behavior modeling obtained by interacting with individuals who have walked the walk in living with epilepsy,” said Martha Sajatovic, MD, Professor of Psychiatry at Case Western Reserve University in Cleveland, and her colleagues.

—Bianca Nogrady

Suggested Reading

Sajatovic M, Colon-Zimmermann K, Kahriman M, et al. A 6-month prospective randomized controlled trial of remotely delivered group format epilepsy self-management versus waitlist control for high-risk people with epilepsy. Epilepsia. 2018;59(9):1684-1695.

Self-management of epilepsy using a group-format, remote intervention improves mood, quality of life, and health functioning in high-risk individuals, according to a randomized, controlled trial published in the September issue of Epilepsia.

In the six-month trial, 120 individuals with epilepsy who had experienced at least one epilepsy-related negative health event in the previous six months were randomized to a wait-list control group or a novel self‐management intervention.

The eight-session intervention, known as SMART, focused on modifiable factors that can be addressed with self-management, such as stress, substance abuse, routine, nutrition, and social support. It was delivered remotely during eight to 10 weeks, either by telephone or online, after an initial in-person session.

“SMART combines the portability and low cost of a Web‐based intervention with the personally salient components of behavior modeling obtained by interacting with individuals who have walked the walk in living with epilepsy,” said Martha Sajatovic, MD, Professor of Psychiatry at Case Western Reserve University in Cleveland, and her colleagues.

—Bianca Nogrady

Suggested Reading

Sajatovic M, Colon-Zimmermann K, Kahriman M, et al. A 6-month prospective randomized controlled trial of remotely delivered group format epilepsy self-management versus waitlist control for high-risk people with epilepsy. Epilepsia. 2018;59(9):1684-1695.

Self-management of epilepsy using a group-format, remote intervention improves mood, quality of life, and health functioning in high-risk individuals, according to a randomized, controlled trial published in the September issue of Epilepsia.

In the six-month trial, 120 individuals with epilepsy who had experienced at least one epilepsy-related negative health event in the previous six months were randomized to a wait-list control group or a novel self‐management intervention.

The eight-session intervention, known as SMART, focused on modifiable factors that can be addressed with self-management, such as stress, substance abuse, routine, nutrition, and social support. It was delivered remotely during eight to 10 weeks, either by telephone or online, after an initial in-person session.

“SMART combines the portability and low cost of a Web‐based intervention with the personally salient components of behavior modeling obtained by interacting with individuals who have walked the walk in living with epilepsy,” said Martha Sajatovic, MD, Professor of Psychiatry at Case Western Reserve University in Cleveland, and her colleagues.

—Bianca Nogrady

Suggested Reading

Sajatovic M, Colon-Zimmermann K, Kahriman M, et al. A 6-month prospective randomized controlled trial of remotely delivered group format epilepsy self-management versus waitlist control for high-risk people with epilepsy. Epilepsia. 2018;59(9):1684-1695.

An estimated 3% of patients with multiple sclerosis (MS) have a benign course of disease, according to findings from a population-based UK study published online ahead of print September 3 in Journal of Neurology, Neurosurgery & Psychiatry. The term “benign MS” remains problematic, however.

“The study of the individuals with extremely favorable outcomes may uncover insights about disease pathogenesis or repair. However, the insensitivity of Expanded Disability Status Scale [EDSS]–based definitions of benign MS and the discrepancy between patient and clinician perception of benign MS undermine use of the term ‘benign’ in the clinical setting,” said Emma Clare Tallantyre, BMBS, PhD, Clinical Senior Lecturer in Neurosciences at Cardiff University in the UK, and her colleagues.

The investigators found that of 1,049 patients with a disease duration of longer than 15 years, 200 had a recent EDSS score of less than 4.0. Of those patients, 60 were clinically assessed, and nine (15%) had benign MS, which was defined as an EDSS score less than 3.0 and lack of significant fatigue, mood disturbance, cognitive impairment, and disruption to employment in the absence of disease-modifying therapy at at least 15 years after symptom onset.

Extrapolating these data, the investigators estimated that 30 patients in the study population of 1,049 had benign MS, yielding a prevalence of 2.9%. Of the 60 patients who were clinically assessed, 39 thought they had benign MS, based on the following definition: “When referring to illness, ‘benign’ usually means a condition which has little or no harmful effects on a person. There are no complications, and there is a good outcome or prognosis.”

Patients who self-reported benign MS had significantly lower EDSS scores, fewer depressive symptoms, lower fatigue severity, and lower reported MS impact than did patients who did not report benign MS. “Self-reported benign MS status showed poor agreement with our composite definition of benign MS status and only fair agreement with EDSS-based definitions of benign MS status,” said the investigators.

—Jeff Evans

Suggested Reading

Tallantyre EC, Major PC, Atherton MJ, et al. How common is truly benign MS in a UK population? J Neurol Neurosurg Psychiatry. 2018 Sep 3 [Epub ahead of print].

An estimated 3% of patients with multiple sclerosis (MS) have a benign course of disease, according to findings from a population-based UK study published online ahead of print September 3 in Journal of Neurology, Neurosurgery & Psychiatry. The term “benign MS” remains problematic, however.

“The study of the individuals with extremely favorable outcomes may uncover insights about disease pathogenesis or repair. However, the insensitivity of Expanded Disability Status Scale [EDSS]–based definitions of benign MS and the discrepancy between patient and clinician perception of benign MS undermine use of the term ‘benign’ in the clinical setting,” said Emma Clare Tallantyre, BMBS, PhD, Clinical Senior Lecturer in Neurosciences at Cardiff University in the UK, and her colleagues.

The investigators found that of 1,049 patients with a disease duration of longer than 15 years, 200 had a recent EDSS score of less than 4.0. Of those patients, 60 were clinically assessed, and nine (15%) had benign MS, which was defined as an EDSS score less than 3.0 and lack of significant fatigue, mood disturbance, cognitive impairment, and disruption to employment in the absence of disease-modifying therapy at at least 15 years after symptom onset.

Extrapolating these data, the investigators estimated that 30 patients in the study population of 1,049 had benign MS, yielding a prevalence of 2.9%. Of the 60 patients who were clinically assessed, 39 thought they had benign MS, based on the following definition: “When referring to illness, ‘benign’ usually means a condition which has little or no harmful effects on a person. There are no complications, and there is a good outcome or prognosis.”

Patients who self-reported benign MS had significantly lower EDSS scores, fewer depressive symptoms, lower fatigue severity, and lower reported MS impact than did patients who did not report benign MS. “Self-reported benign MS status showed poor agreement with our composite definition of benign MS status and only fair agreement with EDSS-based definitions of benign MS status,” said the investigators.

—Jeff Evans

Suggested Reading

Tallantyre EC, Major PC, Atherton MJ, et al. How common is truly benign MS in a UK population? J Neurol Neurosurg Psychiatry. 2018 Sep 3 [Epub ahead of print].

An estimated 3% of patients with multiple sclerosis (MS) have a benign course of disease, according to findings from a population-based UK study published online ahead of print September 3 in Journal of Neurology, Neurosurgery & Psychiatry. The term “benign MS” remains problematic, however.

“The study of the individuals with extremely favorable outcomes may uncover insights about disease pathogenesis or repair. However, the insensitivity of Expanded Disability Status Scale [EDSS]–based definitions of benign MS and the discrepancy between patient and clinician perception of benign MS undermine use of the term ‘benign’ in the clinical setting,” said Emma Clare Tallantyre, BMBS, PhD, Clinical Senior Lecturer in Neurosciences at Cardiff University in the UK, and her colleagues.

The investigators found that of 1,049 patients with a disease duration of longer than 15 years, 200 had a recent EDSS score of less than 4.0. Of those patients, 60 were clinically assessed, and nine (15%) had benign MS, which was defined as an EDSS score less than 3.0 and lack of significant fatigue, mood disturbance, cognitive impairment, and disruption to employment in the absence of disease-modifying therapy at at least 15 years after symptom onset.

Extrapolating these data, the investigators estimated that 30 patients in the study population of 1,049 had benign MS, yielding a prevalence of 2.9%. Of the 60 patients who were clinically assessed, 39 thought they had benign MS, based on the following definition: “When referring to illness, ‘benign’ usually means a condition which has little or no harmful effects on a person. There are no complications, and there is a good outcome or prognosis.”

Patients who self-reported benign MS had significantly lower EDSS scores, fewer depressive symptoms, lower fatigue severity, and lower reported MS impact than did patients who did not report benign MS. “Self-reported benign MS status showed poor agreement with our composite definition of benign MS status and only fair agreement with EDSS-based definitions of benign MS status,” said the investigators.

—Jeff Evans

Suggested Reading

Tallantyre EC, Major PC, Atherton MJ, et al. How common is truly benign MS in a UK population? J Neurol Neurosurg Psychiatry. 2018 Sep 3 [Epub ahead of print].

Spinal muscular atrophy (SMA) is now among the disorders officially included in the Recommended Uniform Screening Panel (RUSP), which state public health departments use to screen newborns for genetic disorders.

Secretary of the Department of Health and Human Services (HHS) Alex M. Azar II formally added SMA to the panel on July 2 on the recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children.

“Adding SMA to the list will help ensure that babies born with SMA are identified, so that they have the opportunity to benefit from early treatment and intervention,” according to a statement from the Muscular Dystrophy Association about the decision. “This testing can also provide families with a genetic diagnosis—information that often is required to determine whether their child is eligible to participate in clinical trials.”

Adding SMA to the RUSP does not mean that states must screen newborns for the disorder. Each state’s public health apparatus decides independently whether to accept the recommendation and which disorders on the RUSP to screen for. Most states screen for most disorders on the RUSP. Evidence compiled by the advisory committee suggested a wide variation in resources, infrastructure, funding, and time to implementation among states.

Drug Approval Raised Ethical Questions

An estimated one in 11,000 newborns has SMA, a disorder caused by mutations in the survival motor neuron 1 (SMN1) gene. SMA affects motor neurons in the brainstem and spinal cord, thus leading to motor weakness and atrophy. The only treatment for SMA had been palliative care until the FDA approved nusinersen for the disorder in December 2016. The drug’s approval has raised ethical questions.^1–3

After reviewing the evidence at its February 8 meeting, the advisory committee recommended adding SMA screening to the RUSP in a March 8 letter from committee chair Joseph A. Bocchini Jr, MD, Professor and Chair of Pediatrics at Louisiana State University Health in Shreveport.

According to Secretary Azar’s summary in his July 2 letter of acceptance, the evidence review suggested that “early screening and treatment can lead to decreased mortality for individuals with SMA and improved motor milestones.”

“SMA can be detected through newborn screening, and treatment is now available that can not only reduce the risk of death, but decrease the development of neurologic impairment,” he said in an interview. “As with adding any condition to newborn screening, public health laboratories will need to develop strategies to incorporate the screening test. The current FDA-approved treatment, nusinersen, is delivered by lumbar puncture into the spinal fluid. In addition, there are exciting advances in gene therapy leading to new treatment approaches.”

Symptom Onset Distinguishes the Types of SMA

Approximately 95% of SMA cases result from the deletion of exon 7 from both alleles of SMN1. Other, rarer cases are caused by mutations in different genes. Without the SMN protein produced by SMN1, a person gradually loses muscle function.

A similar gene, SMN2, also can produce the SMN protein, but in much lower amounts—typically less than 10% of what a person needs. People can, however, have multiple copies of SMN2, which can produce slightly more SMN protein and slow the disease process.

The five types of SMA are determined according to symptom onset, which directly correlates with disorder severity and prognosis. Approximately 54% of SMA cases are Type I, in which progressive weakness occurs over the first six months of life and results in early death. Only 18% of children with Type I live past age 4, and 68% die by age 2. Type 0 is rarer, but more severe, usually causing fetal loss or early infant death.

Type II represents 18% of SMA cases and causes progressive weakness by age 15 months. Most people with Type II survive to their 30s but later experience respiratory failure and rarely reach their 40s. Individuals with Types III and IV typically have a normal lifespan and only begin to see progressive muscle weakness after age 1 or in adulthood.

Dr. Kemper’s group focused on the three types diagnosed in infancy: Types I, II, and III. “It will be critical to make sure that infants diagnosed with SMA through newborn screening receive follow-up shortly afterward to determine whether they would benefit from nusinersen,” said Dr. Kemper. “More information is needed about the long-term outcomes of those infants who begin treatment following newborn screening, so we not only know about outcomes in later childhood and adolescence, but treatment approaches can be further refined and personalized.”

Long-Term Data on Nusinersen Are Lacking

Nusinersen alters the splicing of precursor messenger RNA in SMN2 so that the mRNA strands are longer, which increases the amount of SMN protein produced. Concerns about the medication, however, have included its cost—$750,000 in the first year and $375,000 every following year for life—and potential adverse events from repeated administration. Nusinersen is injected into the spinal canal four times in the first year and once annually thereafter, and the painful injections require patient immobilization. Potential adverse events include thrombocytopenia and nephrotoxicity, along with potential complications from repeated lumbar punctures over time.²

Other concerns about the drug include its limited evidence base, lack of long-term data, associated costs with administration (eg, travel costs), the potential for patients taking nusinersen to be excluded from future clinical trials on other treatments, and ensuring parents have enough information on the drug’s limitations and potential risks to provide adequate informed consent.²

Yet evidence to date is favorable in children with early onset SMA. Dr. Bocchini wrote in the letter to Secretary Azar that “limited data suggest that treatment effect is greater when the treatment is initiated before symptoms develop and when the individual has more copies of SMN2.”

Dr. Kemper’s group concluded that screening can detect SMA in newborns and that treatment can modify the disease course. “Grey literature suggests those with total disease duration less than or equal to 12 weeks before nusinersen treatment were more likely to have better outcomes than those with longer periods of disease duration.

“Presymptomatic treatment alters the natural history” of the disorder, the group found, although outcome data past age 1 are not yet available. Based on findings from a New York pilot program, they predicted that nationwide newborn screening would avert 33 deaths and 48 cases of children who were dependent on a ventilator among an annual cohort of four million births.

At the time of the evidence review, Massachusetts, Minnesota, Missouri, North Carolina, New York, Utah, and Wisconsin initiated pilot programs or whole-population mandated screening for SMA. Of the three states that reported costs, all reported costs of $1 or less per screen.

The research for the evidence review was funded by a Health Resources and Services Administration grant to Duke University in Durham, North Carolina. No disclosures were provided for evidence review group members.

—Tara Haelle

References

1. King NMP, Bishop CE. New treatments for serious conditions: ethical implications. Gene Ther. 2017;24(9):534-538.

2. Gerrity MS, Prasad V, Obley AJ. Concerns about the approval of nusinersen sodium by the US Food and Drug Administration. JAMA Intern Med. 2018;178(6):743-744.

3. Burgart AM, Magnus D, Tabor HK, et al. Ethical challenges confronted when providing nusinersen treatment for spinal muscular atrophy. JAMA Pediatr. 2018;172(2):188-192.

Spinal muscular atrophy (SMA) is now among the disorders officially included in the Recommended Uniform Screening Panel (RUSP), which state public health departments use to screen newborns for genetic disorders.

Secretary of the Department of Health and Human Services (HHS) Alex M. Azar II formally added SMA to the panel on July 2 on the recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children.

“Adding SMA to the list will help ensure that babies born with SMA are identified, so that they have the opportunity to benefit from early treatment and intervention,” according to a statement from the Muscular Dystrophy Association about the decision. “This testing can also provide families with a genetic diagnosis—information that often is required to determine whether their child is eligible to participate in clinical trials.”

Adding SMA to the RUSP does not mean that states must screen newborns for the disorder. Each state’s public health apparatus decides independently whether to accept the recommendation and which disorders on the RUSP to screen for. Most states screen for most disorders on the RUSP. Evidence compiled by the advisory committee suggested a wide variation in resources, infrastructure, funding, and time to implementation among states.

Drug Approval Raised Ethical Questions

An estimated one in 11,000 newborns has SMA, a disorder caused by mutations in the survival motor neuron 1 (SMN1) gene. SMA affects motor neurons in the brainstem and spinal cord, thus leading to motor weakness and atrophy. The only treatment for SMA had been palliative care until the FDA approved nusinersen for the disorder in December 2016. The drug’s approval has raised ethical questions.^1–3

After reviewing the evidence at its February 8 meeting, the advisory committee recommended adding SMA screening to the RUSP in a March 8 letter from committee chair Joseph A. Bocchini Jr, MD, Professor and Chair of Pediatrics at Louisiana State University Health in Shreveport.

According to Secretary Azar’s summary in his July 2 letter of acceptance, the evidence review suggested that “early screening and treatment can lead to decreased mortality for individuals with SMA and improved motor milestones.”

“SMA can be detected through newborn screening, and treatment is now available that can not only reduce the risk of death, but decrease the development of neurologic impairment,” he said in an interview. “As with adding any condition to newborn screening, public health laboratories will need to develop strategies to incorporate the screening test. The current FDA-approved treatment, nusinersen, is delivered by lumbar puncture into the spinal fluid. In addition, there are exciting advances in gene therapy leading to new treatment approaches.”

Symptom Onset Distinguishes the Types of SMA

Approximately 95% of SMA cases result from the deletion of exon 7 from both alleles of SMN1. Other, rarer cases are caused by mutations in different genes. Without the SMN protein produced by SMN1, a person gradually loses muscle function.

A similar gene, SMN2, also can produce the SMN protein, but in much lower amounts—typically less than 10% of what a person needs. People can, however, have multiple copies of SMN2, which can produce slightly more SMN protein and slow the disease process.

The five types of SMA are determined according to symptom onset, which directly correlates with disorder severity and prognosis. Approximately 54% of SMA cases are Type I, in which progressive weakness occurs over the first six months of life and results in early death. Only 18% of children with Type I live past age 4, and 68% die by age 2. Type 0 is rarer, but more severe, usually causing fetal loss or early infant death.

Type II represents 18% of SMA cases and causes progressive weakness by age 15 months. Most people with Type II survive to their 30s but later experience respiratory failure and rarely reach their 40s. Individuals with Types III and IV typically have a normal lifespan and only begin to see progressive muscle weakness after age 1 or in adulthood.

Dr. Kemper’s group focused on the three types diagnosed in infancy: Types I, II, and III. “It will be critical to make sure that infants diagnosed with SMA through newborn screening receive follow-up shortly afterward to determine whether they would benefit from nusinersen,” said Dr. Kemper. “More information is needed about the long-term outcomes of those infants who begin treatment following newborn screening, so we not only know about outcomes in later childhood and adolescence, but treatment approaches can be further refined and personalized.”

Long-Term Data on Nusinersen Are Lacking

Nusinersen alters the splicing of precursor messenger RNA in SMN2 so that the mRNA strands are longer, which increases the amount of SMN protein produced. Concerns about the medication, however, have included its cost—$750,000 in the first year and $375,000 every following year for life—and potential adverse events from repeated administration. Nusinersen is injected into the spinal canal four times in the first year and once annually thereafter, and the painful injections require patient immobilization. Potential adverse events include thrombocytopenia and nephrotoxicity, along with potential complications from repeated lumbar punctures over time.²

Other concerns about the drug include its limited evidence base, lack of long-term data, associated costs with administration (eg, travel costs), the potential for patients taking nusinersen to be excluded from future clinical trials on other treatments, and ensuring parents have enough information on the drug’s limitations and potential risks to provide adequate informed consent.²

Yet evidence to date is favorable in children with early onset SMA. Dr. Bocchini wrote in the letter to Secretary Azar that “limited data suggest that treatment effect is greater when the treatment is initiated before symptoms develop and when the individual has more copies of SMN2.”

Dr. Kemper’s group concluded that screening can detect SMA in newborns and that treatment can modify the disease course. “Grey literature suggests those with total disease duration less than or equal to 12 weeks before nusinersen treatment were more likely to have better outcomes than those with longer periods of disease duration.

“Presymptomatic treatment alters the natural history” of the disorder, the group found, although outcome data past age 1 are not yet available. Based on findings from a New York pilot program, they predicted that nationwide newborn screening would avert 33 deaths and 48 cases of children who were dependent on a ventilator among an annual cohort of four million births.

At the time of the evidence review, Massachusetts, Minnesota, Missouri, North Carolina, New York, Utah, and Wisconsin initiated pilot programs or whole-population mandated screening for SMA. Of the three states that reported costs, all reported costs of $1 or less per screen.

The research for the evidence review was funded by a Health Resources and Services Administration grant to Duke University in Durham, North Carolina. No disclosures were provided for evidence review group members.

—Tara Haelle

References

1. King NMP, Bishop CE. New treatments for serious conditions: ethical implications. Gene Ther. 2017;24(9):534-538.

2. Gerrity MS, Prasad V, Obley AJ. Concerns about the approval of nusinersen sodium by the US Food and Drug Administration. JAMA Intern Med. 2018;178(6):743-744.

3. Burgart AM, Magnus D, Tabor HK, et al. Ethical challenges confronted when providing nusinersen treatment for spinal muscular atrophy. JAMA Pediatr. 2018;172(2):188-192.

Spinal muscular atrophy (SMA) is now among the disorders officially included in the Recommended Uniform Screening Panel (RUSP), which state public health departments use to screen newborns for genetic disorders.

Secretary of the Department of Health and Human Services (HHS) Alex M. Azar II formally added SMA to the panel on July 2 on the recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children.

“Adding SMA to the list will help ensure that babies born with SMA are identified, so that they have the opportunity to benefit from early treatment and intervention,” according to a statement from the Muscular Dystrophy Association about the decision. “This testing can also provide families with a genetic diagnosis—information that often is required to determine whether their child is eligible to participate in clinical trials.”

Adding SMA to the RUSP does not mean that states must screen newborns for the disorder. Each state’s public health apparatus decides independently whether to accept the recommendation and which disorders on the RUSP to screen for. Most states screen for most disorders on the RUSP. Evidence compiled by the advisory committee suggested a wide variation in resources, infrastructure, funding, and time to implementation among states.

Drug Approval Raised Ethical Questions

An estimated one in 11,000 newborns has SMA, a disorder caused by mutations in the survival motor neuron 1 (SMN1) gene. SMA affects motor neurons in the brainstem and spinal cord, thus leading to motor weakness and atrophy. The only treatment for SMA had been palliative care until the FDA approved nusinersen for the disorder in December 2016. The drug’s approval has raised ethical questions.^1–3

After reviewing the evidence at its February 8 meeting, the advisory committee recommended adding SMA screening to the RUSP in a March 8 letter from committee chair Joseph A. Bocchini Jr, MD, Professor and Chair of Pediatrics at Louisiana State University Health in Shreveport.

According to Secretary Azar’s summary in his July 2 letter of acceptance, the evidence review suggested that “early screening and treatment can lead to decreased mortality for individuals with SMA and improved motor milestones.”

“SMA can be detected through newborn screening, and treatment is now available that can not only reduce the risk of death, but decrease the development of neurologic impairment,” he said in an interview. “As with adding any condition to newborn screening, public health laboratories will need to develop strategies to incorporate the screening test. The current FDA-approved treatment, nusinersen, is delivered by lumbar puncture into the spinal fluid. In addition, there are exciting advances in gene therapy leading to new treatment approaches.”

Symptom Onset Distinguishes the Types of SMA

Approximately 95% of SMA cases result from the deletion of exon 7 from both alleles of SMN1. Other, rarer cases are caused by mutations in different genes. Without the SMN protein produced by SMN1, a person gradually loses muscle function.

A similar gene, SMN2, also can produce the SMN protein, but in much lower amounts—typically less than 10% of what a person needs. People can, however, have multiple copies of SMN2, which can produce slightly more SMN protein and slow the disease process.

The five types of SMA are determined according to symptom onset, which directly correlates with disorder severity and prognosis. Approximately 54% of SMA cases are Type I, in which progressive weakness occurs over the first six months of life and results in early death. Only 18% of children with Type I live past age 4, and 68% die by age 2. Type 0 is rarer, but more severe, usually causing fetal loss or early infant death.

Type II represents 18% of SMA cases and causes progressive weakness by age 15 months. Most people with Type II survive to their 30s but later experience respiratory failure and rarely reach their 40s. Individuals with Types III and IV typically have a normal lifespan and only begin to see progressive muscle weakness after age 1 or in adulthood.

Dr. Kemper’s group focused on the three types diagnosed in infancy: Types I, II, and III. “It will be critical to make sure that infants diagnosed with SMA through newborn screening receive follow-up shortly afterward to determine whether they would benefit from nusinersen,” said Dr. Kemper. “More information is needed about the long-term outcomes of those infants who begin treatment following newborn screening, so we not only know about outcomes in later childhood and adolescence, but treatment approaches can be further refined and personalized.”

Long-Term Data on Nusinersen Are Lacking

Nusinersen alters the splicing of precursor messenger RNA in SMN2 so that the mRNA strands are longer, which increases the amount of SMN protein produced. Concerns about the medication, however, have included its cost—$750,000 in the first year and $375,000 every following year for life—and potential adverse events from repeated administration. Nusinersen is injected into the spinal canal four times in the first year and once annually thereafter, and the painful injections require patient immobilization. Potential adverse events include thrombocytopenia and nephrotoxicity, along with potential complications from repeated lumbar punctures over time.²

Other concerns about the drug include its limited evidence base, lack of long-term data, associated costs with administration (eg, travel costs), the potential for patients taking nusinersen to be excluded from future clinical trials on other treatments, and ensuring parents have enough information on the drug’s limitations and potential risks to provide adequate informed consent.²

Yet evidence to date is favorable in children with early onset SMA. Dr. Bocchini wrote in the letter to Secretary Azar that “limited data suggest that treatment effect is greater when the treatment is initiated before symptoms develop and when the individual has more copies of SMN2.”

Dr. Kemper’s group concluded that screening can detect SMA in newborns and that treatment can modify the disease course. “Grey literature suggests those with total disease duration less than or equal to 12 weeks before nusinersen treatment were more likely to have better outcomes than those with longer periods of disease duration.

“Presymptomatic treatment alters the natural history” of the disorder, the group found, although outcome data past age 1 are not yet available. Based on findings from a New York pilot program, they predicted that nationwide newborn screening would avert 33 deaths and 48 cases of children who were dependent on a ventilator among an annual cohort of four million births.

At the time of the evidence review, Massachusetts, Minnesota, Missouri, North Carolina, New York, Utah, and Wisconsin initiated pilot programs or whole-population mandated screening for SMA. Of the three states that reported costs, all reported costs of $1 or less per screen.

The research for the evidence review was funded by a Health Resources and Services Administration grant to Duke University in Durham, North Carolina. No disclosures were provided for evidence review group members.

—Tara Haelle

References

1. King NMP, Bishop CE. New treatments for serious conditions: ethical implications. Gene Ther. 2017;24(9):534-538.

2. Gerrity MS, Prasad V, Obley AJ. Concerns about the approval of nusinersen sodium by the US Food and Drug Administration. JAMA Intern Med. 2018;178(6):743-744.

3. Burgart AM, Magnus D, Tabor HK, et al. Ethical challenges confronted when providing nusinersen treatment for spinal muscular atrophy. JAMA Pediatr. 2018;172(2):188-192.

Residents of Denmark who seek medical attention for traumatic brain injury (TBI) have an increased risk of suicide, compared with the general Danish population without TBI, according to a study published in the August 14 issue of JAMA. “Additional analyses revealed that the risk of suicide was higher for individuals with severe TBI, numerous medical contacts, and longer hospital stays,” said lead author Trine Madsen, PhD. Individuals were at highest risk in the first six months after discharge, said Dr. Madsen, who is a postdoctoral fellow at the Danish Research Institute for Suicide Prevention in Hellerup.

A history of TBI previously has been associated with higher rates of self-harm, suicide, and death than are found in the general population. However, previous studies have been limited by methodological shortcomings, such as small sample sizes and low numbers of suicide cases with TBI. Dr. Madsen and colleagues conducted a retrospective cohort study using nationwide registers covering 7,418,391 individuals living in Denmark between 1980 and 2014 with 164,265,624 person-years’ follow-up. Of these people, 567,823 (7.6%) had a medical contact for TBI, which included mild TBI (ie, concussion), skull fracture without documented TBI, and severe TBI (ie, head injuries with evidence of structural brain injury).

Of 34,529 individuals who died by suicide, 3,536 (10.2%) had medical contact for TBI, including 2,701 for mild TBI, 174 for skull fracture without documented TBI, and 661 for severe TBI. The absolute suicide rate was 41 per 100,000 person-years among those with TBI versus 20 per 100,000 person-years among those with no diagnosis of TBI. After accounting for relevant covariates such as fractures not involving the skull, psychiatric diagnoses, and deliberate self-harm, the adjusted incidence ratio was 1.90.

This study “provides insights into the underappreciated relationship between TBI and suicide,” said Lee Goldstein, MD, PhD, and Ramon Diaz-Arrastia, MD, PhD, in an accompanying editorial. “The results … point to an important clinical triad—TBI history, recent injury (especially with long hospital stays), and more numerous postinjury medical contacts for TBI—that serves as a red flag for increased suicide risk,” said Dr. Goldstein, who is affiliated with Boston University School of Medicine, and Dr. Diaz-Arrastia, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia. The results “indicate that increased suicide risk is relevant across all TBI severity levels, including the far more common mild injuries. Clinicians, health care professionals, and mental health practitioners must take notice of this important information.”

—Glenn S. Williams

Suggested Reading

Goldstein L, Diaz-Arrastia R. Traumatic brain injury and risk of suicide. JAMA. 2018;320(6):554-556.

Madsen T, Erlangsen A, Orlovska S, et al. Association between traumatic brain injury and risk of suicide. JAMA. 2018;320(6):580-588.

Residents of Denmark who seek medical attention for traumatic brain injury (TBI) have an increased risk of suicide, compared with the general Danish population without TBI, according to a study published in the August 14 issue of JAMA. “Additional analyses revealed that the risk of suicide was higher for individuals with severe TBI, numerous medical contacts, and longer hospital stays,” said lead author Trine Madsen, PhD. Individuals were at highest risk in the first six months after discharge, said Dr. Madsen, who is a postdoctoral fellow at the Danish Research Institute for Suicide Prevention in Hellerup.

A history of TBI previously has been associated with higher rates of self-harm, suicide, and death than are found in the general population. However, previous studies have been limited by methodological shortcomings, such as small sample sizes and low numbers of suicide cases with TBI. Dr. Madsen and colleagues conducted a retrospective cohort study using nationwide registers covering 7,418,391 individuals living in Denmark between 1980 and 2014 with 164,265,624 person-years’ follow-up. Of these people, 567,823 (7.6%) had a medical contact for TBI, which included mild TBI (ie, concussion), skull fracture without documented TBI, and severe TBI (ie, head injuries with evidence of structural brain injury).

Of 34,529 individuals who died by suicide, 3,536 (10.2%) had medical contact for TBI, including 2,701 for mild TBI, 174 for skull fracture without documented TBI, and 661 for severe TBI. The absolute suicide rate was 41 per 100,000 person-years among those with TBI versus 20 per 100,000 person-years among those with no diagnosis of TBI. After accounting for relevant covariates such as fractures not involving the skull, psychiatric diagnoses, and deliberate self-harm, the adjusted incidence ratio was 1.90.

This study “provides insights into the underappreciated relationship between TBI and suicide,” said Lee Goldstein, MD, PhD, and Ramon Diaz-Arrastia, MD, PhD, in an accompanying editorial. “The results … point to an important clinical triad—TBI history, recent injury (especially with long hospital stays), and more numerous postinjury medical contacts for TBI—that serves as a red flag for increased suicide risk,” said Dr. Goldstein, who is affiliated with Boston University School of Medicine, and Dr. Diaz-Arrastia, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia. The results “indicate that increased suicide risk is relevant across all TBI severity levels, including the far more common mild injuries. Clinicians, health care professionals, and mental health practitioners must take notice of this important information.”

—Glenn S. Williams

Suggested Reading

Goldstein L, Diaz-Arrastia R. Traumatic brain injury and risk of suicide. JAMA. 2018;320(6):554-556.

Madsen T, Erlangsen A, Orlovska S, et al. Association between traumatic brain injury and risk of suicide. JAMA. 2018;320(6):580-588.

Residents of Denmark who seek medical attention for traumatic brain injury (TBI) have an increased risk of suicide, compared with the general Danish population without TBI, according to a study published in the August 14 issue of JAMA. “Additional analyses revealed that the risk of suicide was higher for individuals with severe TBI, numerous medical contacts, and longer hospital stays,” said lead author Trine Madsen, PhD. Individuals were at highest risk in the first six months after discharge, said Dr. Madsen, who is a postdoctoral fellow at the Danish Research Institute for Suicide Prevention in Hellerup.

A history of TBI previously has been associated with higher rates of self-harm, suicide, and death than are found in the general population. However, previous studies have been limited by methodological shortcomings, such as small sample sizes and low numbers of suicide cases with TBI. Dr. Madsen and colleagues conducted a retrospective cohort study using nationwide registers covering 7,418,391 individuals living in Denmark between 1980 and 2014 with 164,265,624 person-years’ follow-up. Of these people, 567,823 (7.6%) had a medical contact for TBI, which included mild TBI (ie, concussion), skull fracture without documented TBI, and severe TBI (ie, head injuries with evidence of structural brain injury).

Of 34,529 individuals who died by suicide, 3,536 (10.2%) had medical contact for TBI, including 2,701 for mild TBI, 174 for skull fracture without documented TBI, and 661 for severe TBI. The absolute suicide rate was 41 per 100,000 person-years among those with TBI versus 20 per 100,000 person-years among those with no diagnosis of TBI. After accounting for relevant covariates such as fractures not involving the skull, psychiatric diagnoses, and deliberate self-harm, the adjusted incidence ratio was 1.90.

This study “provides insights into the underappreciated relationship between TBI and suicide,” said Lee Goldstein, MD, PhD, and Ramon Diaz-Arrastia, MD, PhD, in an accompanying editorial. “The results … point to an important clinical triad—TBI history, recent injury (especially with long hospital stays), and more numerous postinjury medical contacts for TBI—that serves as a red flag for increased suicide risk,” said Dr. Goldstein, who is affiliated with Boston University School of Medicine, and Dr. Diaz-Arrastia, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia. The results “indicate that increased suicide risk is relevant across all TBI severity levels, including the far more common mild injuries. Clinicians, health care professionals, and mental health practitioners must take notice of this important information.”

—Glenn S. Williams

Suggested Reading

Goldstein L, Diaz-Arrastia R. Traumatic brain injury and risk of suicide. JAMA. 2018;320(6):554-556.

Madsen T, Erlangsen A, Orlovska S, et al. Association between traumatic brain injury and risk of suicide. JAMA. 2018;320(6):580-588.

The prodrome of multiple sclerosis (MS) may include an increased risk of nervous system, sensory, and musculoskeletal disorders, according to research published online ahead of print July 1 in Multiple Sclerosis Journal. Patients who later develop MS also may be more likely to have genitourinary and psychiatric symptoms in the five years before diagnosis.

“The existence of such warning signs is well-accepted for Alzheimer’s disease and Parkinson’s disease, but there has been little investigation into a similar pattern for MS,” said Helen Tremlett, PhD, Professor in the Division of Neurology at the University of British Columbia in Canada. “We now need to delve deeper into this phenomenon, perhaps using data-mining techniques. We want to see if there are discernible patterns related to sex, age, or the type of MS they eventually develop.”

Clinical and Administrative Matched Cohorts

Dr. Tremlett and colleagues analyzed data from a matched-cohort record-linkage study to examine the MS prodrome. The investigators used population-based health administrative data and clinical data from the Canadian provinces of British Columbia, Saskatchewan, Manitoba, and Nova Scotia. The information included demographics, hospital visits, physician encounters, and prescriptions filled. Clinical data were for patients diagnosed by a neurologist at an MS clinic and included first clinical visit (or date of diagnosis) and date of symptom onset. Data were collected from April 1984 to April 2014.

Using the data, Dr. Tremlett and colleagues created a health-administrative cohort and a clinical cohort. The clinical cohort did not include data from Saskatchewan. To create the cohorts, the investigators identified patients with MS and matched them by sex, year of birth, and postal code with as many as five controls. The index date was the earliest recorded claim for a demyelinating disease for the health-administrative cohort and the date of MS symptom onset for the clinical cohort. Study outcomes were the number of physician and hospital encounters per ICD-10 chapter, the number of physician encounters per physician specialty, and the percentage of people with one or more prescriptions per drug class in the five years before the index date.

Clinical Cohort Results May Be More Accurate

The administrative cohort included 13,951 cases and 66,940 controls. The clinical cohort included 3,202 cases and 16,006 controls. Compared with controls, people with MS had more physician and hospital encounters for the nervous (rate ratio [RR], 2.31 to 4.75), sensory (RR, 1.40 to 2.28), musculoskeletal (RR, 1.19 to 1.70), and genitourinary systems (RR, 1.17 to 1.59) in the five years before the first demyelinating claim or symptom onset. Cases had more visits with psychiatrists and urologists (RR, 1.48 to 1.80) and higher proportions of musculoskeletal, genitourinary, or hormonal-related prescriptions (1.1–1.5 times higher), compared with controls. People with MS had fewer pregnancy-related encounters than controls, however (RR, 0.78 to 0.88).

The “more conservative” results for the clinical cohort are more likely to reflect the MS prodrome accurately because they are “unlikely to be influenced by a physician’s suspicion or consideration of MS,” said Dr. Tremlett and colleagues. “Although not all individuals with MS attend an MS specialty clinic, the clinical cohort represents a subgroup of the population that may differ with respect to demographic and clinical characteristics from nonclinic attendees (eg, have fewer comorbidities),” they added. NR

—Erik Greb

Suggested Reading

Wijnands JM, Zhu F, Kingwell E, et al. Five years before multiple sclerosis onset: Phenotyping the prodrome. Mult Scler. 2018 Jul 1 [Epub ahead of print].

The prodrome of multiple sclerosis (MS) may include an increased risk of nervous system, sensory, and musculoskeletal disorders, according to research published online ahead of print July 1 in Multiple Sclerosis Journal. Patients who later develop MS also may be more likely to have genitourinary and psychiatric symptoms in the five years before diagnosis.

“The existence of such warning signs is well-accepted for Alzheimer’s disease and Parkinson’s disease, but there has been little investigation into a similar pattern for MS,” said Helen Tremlett, PhD, Professor in the Division of Neurology at the University of British Columbia in Canada. “We now need to delve deeper into this phenomenon, perhaps using data-mining techniques. We want to see if there are discernible patterns related to sex, age, or the type of MS they eventually develop.”

Clinical and Administrative Matched Cohorts

Dr. Tremlett and colleagues analyzed data from a matched-cohort record-linkage study to examine the MS prodrome. The investigators used population-based health administrative data and clinical data from the Canadian provinces of British Columbia, Saskatchewan, Manitoba, and Nova Scotia. The information included demographics, hospital visits, physician encounters, and prescriptions filled. Clinical data were for patients diagnosed by a neurologist at an MS clinic and included first clinical visit (or date of diagnosis) and date of symptom onset. Data were collected from April 1984 to April 2014.

Using the data, Dr. Tremlett and colleagues created a health-administrative cohort and a clinical cohort. The clinical cohort did not include data from Saskatchewan. To create the cohorts, the investigators identified patients with MS and matched them by sex, year of birth, and postal code with as many as five controls. The index date was the earliest recorded claim for a demyelinating disease for the health-administrative cohort and the date of MS symptom onset for the clinical cohort. Study outcomes were the number of physician and hospital encounters per ICD-10 chapter, the number of physician encounters per physician specialty, and the percentage of people with one or more prescriptions per drug class in the five years before the index date.

Clinical Cohort Results May Be More Accurate

The administrative cohort included 13,951 cases and 66,940 controls. The clinical cohort included 3,202 cases and 16,006 controls. Compared with controls, people with MS had more physician and hospital encounters for the nervous (rate ratio [RR], 2.31 to 4.75), sensory (RR, 1.40 to 2.28), musculoskeletal (RR, 1.19 to 1.70), and genitourinary systems (RR, 1.17 to 1.59) in the five years before the first demyelinating claim or symptom onset. Cases had more visits with psychiatrists and urologists (RR, 1.48 to 1.80) and higher proportions of musculoskeletal, genitourinary, or hormonal-related prescriptions (1.1–1.5 times higher), compared with controls. People with MS had fewer pregnancy-related encounters than controls, however (RR, 0.78 to 0.88).

The “more conservative” results for the clinical cohort are more likely to reflect the MS prodrome accurately because they are “unlikely to be influenced by a physician’s suspicion or consideration of MS,” said Dr. Tremlett and colleagues. “Although not all individuals with MS attend an MS specialty clinic, the clinical cohort represents a subgroup of the population that may differ with respect to demographic and clinical characteristics from nonclinic attendees (eg, have fewer comorbidities),” they added. NR

—Erik Greb

Suggested Reading

Wijnands JM, Zhu F, Kingwell E, et al. Five years before multiple sclerosis onset: Phenotyping the prodrome. Mult Scler. 2018 Jul 1 [Epub ahead of print].

The prodrome of multiple sclerosis (MS) may include an increased risk of nervous system, sensory, and musculoskeletal disorders, according to research published online ahead of print July 1 in Multiple Sclerosis Journal. Patients who later develop MS also may be more likely to have genitourinary and psychiatric symptoms in the five years before diagnosis.

“The existence of such warning signs is well-accepted for Alzheimer’s disease and Parkinson’s disease, but there has been little investigation into a similar pattern for MS,” said Helen Tremlett, PhD, Professor in the Division of Neurology at the University of British Columbia in Canada. “We now need to delve deeper into this phenomenon, perhaps using data-mining techniques. We want to see if there are discernible patterns related to sex, age, or the type of MS they eventually develop.”

Clinical and Administrative Matched Cohorts

Dr. Tremlett and colleagues analyzed data from a matched-cohort record-linkage study to examine the MS prodrome. The investigators used population-based health administrative data and clinical data from the Canadian provinces of British Columbia, Saskatchewan, Manitoba, and Nova Scotia. The information included demographics, hospital visits, physician encounters, and prescriptions filled. Clinical data were for patients diagnosed by a neurologist at an MS clinic and included first clinical visit (or date of diagnosis) and date of symptom onset. Data were collected from April 1984 to April 2014.

Using the data, Dr. Tremlett and colleagues created a health-administrative cohort and a clinical cohort. The clinical cohort did not include data from Saskatchewan. To create the cohorts, the investigators identified patients with MS and matched them by sex, year of birth, and postal code with as many as five controls. The index date was the earliest recorded claim for a demyelinating disease for the health-administrative cohort and the date of MS symptom onset for the clinical cohort. Study outcomes were the number of physician and hospital encounters per ICD-10 chapter, the number of physician encounters per physician specialty, and the percentage of people with one or more prescriptions per drug class in the five years before the index date.

Clinical Cohort Results May Be More Accurate

The administrative cohort included 13,951 cases and 66,940 controls. The clinical cohort included 3,202 cases and 16,006 controls. Compared with controls, people with MS had more physician and hospital encounters for the nervous (rate ratio [RR], 2.31 to 4.75), sensory (RR, 1.40 to 2.28), musculoskeletal (RR, 1.19 to 1.70), and genitourinary systems (RR, 1.17 to 1.59) in the five years before the first demyelinating claim or symptom onset. Cases had more visits with psychiatrists and urologists (RR, 1.48 to 1.80) and higher proportions of musculoskeletal, genitourinary, or hormonal-related prescriptions (1.1–1.5 times higher), compared with controls. People with MS had fewer pregnancy-related encounters than controls, however (RR, 0.78 to 0.88).

The “more conservative” results for the clinical cohort are more likely to reflect the MS prodrome accurately because they are “unlikely to be influenced by a physician’s suspicion or consideration of MS,” said Dr. Tremlett and colleagues. “Although not all individuals with MS attend an MS specialty clinic, the clinical cohort represents a subgroup of the population that may differ with respect to demographic and clinical characteristics from nonclinic attendees (eg, have fewer comorbidities),” they added. NR

—Erik Greb

Suggested Reading

Wijnands JM, Zhu F, Kingwell E, et al. Five years before multiple sclerosis onset: Phenotyping the prodrome. Mult Scler. 2018 Jul 1 [Epub ahead of print].

Patients with type 2 diabetes mellitus have an increased risk of developing Parkinson’s disease later in life, according to an investigation published online ahead of print June 13 in Neurology. The magnitude of risk is greater in younger patients and in patients with complications from diabetes.

Investigators have hypothesized an association between diabetes and the risk of Parkinson’s disease, but studies of the potential link have had conflicting results. Thomas T. Warner, MD, PhD, Professor of Clinical Neurology at University College London (UCL), and colleagues conducted a retrospective cohort study to examine this question anew.

Analyzing a Nationwide Hospital Database

The researchers reviewed English national Hospital Episode Statistics and mortality data collected between 1999 and 2011 and created a cohort of 2,017,115 patients who had been admitted for hospital care with a diagnosis of type 2 diabetes. They created a reference cohort of 6,173,208 patients without diabetes who were admitted for minor medical and surgical procedures. Conditions in this cohort included sprains, inguinal hernia, bruising, and hip replacement. People with Parkinson’s disease, ischemic cerebral infarction, vascular parkinsonism, drug-induced secondary parkinsonism, and normal pressure hydrocephalus were excluded from the study. Dr. Warner and colleagues created multivariable Cox proportional hazard regression models to estimate the risk of subsequent Parkinson’s disease.

Participants with diabetes had a greater risk of a subsequent diagnosis of Parkinson’s disease than patients in the reference cohort (adjusted hazard ratio [HR], 1.32). In subgroup analyses, the researchers found that the risk was substantially higher among patients between ages 25 and 44 (adjusted HR, 3.81) and those with complicated diabetes (adjusted HR, 1.49). Genetic factors may exert a relatively greater effect on younger people, and this difference may account for the increased risk among younger participants with diabetes, said the authors.

The adjusted HR of Parkinson’s disease was 1.40 in patients with diabetes between ages 65 and 74 and 1.18 in those age 75 or older. “The association in elderly patients may be the consequence of disrupted insulin signaling secondary to additional lifestyle and environmental factors causing cumulative pathogenic brain changes,” said Dr. Warner and colleagues.

No Adjustment for Potential Confounders

The large size of the database and the ability to exclude people with cerebrovascular disease and drug-induced and vascular parkinsonisms were among the study’s main strengths, according to the authors. Its weaknesses included an inability to adjust for potential confounders and the lack of clinical information about Parkinson’s disease ascertainment beyond routinely collected data.

The results could help researchers identify “new ways to treat or prevent the development of Parkinson’s disease, such as use of antidiabetes drugs to restore the brain’s insulin signaling,” said Dr. Warner. “A UCL-led study published last year found that a drug commonly used to treat diabetes shows promise in not only relieving Parkinson’s disease symptoms, but potentially altering the course of the disease itself. What we do not know is whether trying to treat people with type 2 diabetes better would reduce the risk of developing Parkinson’s disease.”

—Erik Greb

Suggested Reading

De Pablo-Fernandez E, Goldacre R, Pakpoor J, et al. Association between diabetes and subsequent Parkinson disease: a record-linkage cohort study. Neurology. 2018 Jun 13 [Epub ahead of print].

Patients with type 2 diabetes mellitus have an increased risk of developing Parkinson’s disease later in life, according to an investigation published online ahead of print June 13 in Neurology. The magnitude of risk is greater in younger patients and in patients with complications from diabetes.

Investigators have hypothesized an association between diabetes and the risk of Parkinson’s disease, but studies of the potential link have had conflicting results. Thomas T. Warner, MD, PhD, Professor of Clinical Neurology at University College London (UCL), and colleagues conducted a retrospective cohort study to examine this question anew.

Analyzing a Nationwide Hospital Database

The researchers reviewed English national Hospital Episode Statistics and mortality data collected between 1999 and 2011 and created a cohort of 2,017,115 patients who had been admitted for hospital care with a diagnosis of type 2 diabetes. They created a reference cohort of 6,173,208 patients without diabetes who were admitted for minor medical and surgical procedures. Conditions in this cohort included sprains, inguinal hernia, bruising, and hip replacement. People with Parkinson’s disease, ischemic cerebral infarction, vascular parkinsonism, drug-induced secondary parkinsonism, and normal pressure hydrocephalus were excluded from the study. Dr. Warner and colleagues created multivariable Cox proportional hazard regression models to estimate the risk of subsequent Parkinson’s disease.

Participants with diabetes had a greater risk of a subsequent diagnosis of Parkinson’s disease than patients in the reference cohort (adjusted hazard ratio [HR], 1.32). In subgroup analyses, the researchers found that the risk was substantially higher among patients between ages 25 and 44 (adjusted HR, 3.81) and those with complicated diabetes (adjusted HR, 1.49). Genetic factors may exert a relatively greater effect on younger people, and this difference may account for the increased risk among younger participants with diabetes, said the authors.

The adjusted HR of Parkinson’s disease was 1.40 in patients with diabetes between ages 65 and 74 and 1.18 in those age 75 or older. “The association in elderly patients may be the consequence of disrupted insulin signaling secondary to additional lifestyle and environmental factors causing cumulative pathogenic brain changes,” said Dr. Warner and colleagues.

No Adjustment for Potential Confounders

The large size of the database and the ability to exclude people with cerebrovascular disease and drug-induced and vascular parkinsonisms were among the study’s main strengths, according to the authors. Its weaknesses included an inability to adjust for potential confounders and the lack of clinical information about Parkinson’s disease ascertainment beyond routinely collected data.

The results could help researchers identify “new ways to treat or prevent the development of Parkinson’s disease, such as use of antidiabetes drugs to restore the brain’s insulin signaling,” said Dr. Warner. “A UCL-led study published last year found that a drug commonly used to treat diabetes shows promise in not only relieving Parkinson’s disease symptoms, but potentially altering the course of the disease itself. What we do not know is whether trying to treat people with type 2 diabetes better would reduce the risk of developing Parkinson’s disease.”

—Erik Greb

Suggested Reading

De Pablo-Fernandez E, Goldacre R, Pakpoor J, et al. Association between diabetes and subsequent Parkinson disease: a record-linkage cohort study. Neurology. 2018 Jun 13 [Epub ahead of print].

Patients with type 2 diabetes mellitus have an increased risk of developing Parkinson’s disease later in life, according to an investigation published online ahead of print June 13 in Neurology. The magnitude of risk is greater in younger patients and in patients with complications from diabetes.

Investigators have hypothesized an association between diabetes and the risk of Parkinson’s disease, but studies of the potential link have had conflicting results. Thomas T. Warner, MD, PhD, Professor of Clinical Neurology at University College London (UCL), and colleagues conducted a retrospective cohort study to examine this question anew.

Analyzing a Nationwide Hospital Database

The researchers reviewed English national Hospital Episode Statistics and mortality data collected between 1999 and 2011 and created a cohort of 2,017,115 patients who had been admitted for hospital care with a diagnosis of type 2 diabetes. They created a reference cohort of 6,173,208 patients without diabetes who were admitted for minor medical and surgical procedures. Conditions in this cohort included sprains, inguinal hernia, bruising, and hip replacement. People with Parkinson’s disease, ischemic cerebral infarction, vascular parkinsonism, drug-induced secondary parkinsonism, and normal pressure hydrocephalus were excluded from the study. Dr. Warner and colleagues created multivariable Cox proportional hazard regression models to estimate the risk of subsequent Parkinson’s disease.

Participants with diabetes had a greater risk of a subsequent diagnosis of Parkinson’s disease than patients in the reference cohort (adjusted hazard ratio [HR], 1.32). In subgroup analyses, the researchers found that the risk was substantially higher among patients between ages 25 and 44 (adjusted HR, 3.81) and those with complicated diabetes (adjusted HR, 1.49). Genetic factors may exert a relatively greater effect on younger people, and this difference may account for the increased risk among younger participants with diabetes, said the authors.

The adjusted HR of Parkinson’s disease was 1.40 in patients with diabetes between ages 65 and 74 and 1.18 in those age 75 or older. “The association in elderly patients may be the consequence of disrupted insulin signaling secondary to additional lifestyle and environmental factors causing cumulative pathogenic brain changes,” said Dr. Warner and colleagues.

No Adjustment for Potential Confounders

The large size of the database and the ability to exclude people with cerebrovascular disease and drug-induced and vascular parkinsonisms were among the study’s main strengths, according to the authors. Its weaknesses included an inability to adjust for potential confounders and the lack of clinical information about Parkinson’s disease ascertainment beyond routinely collected data.

The results could help researchers identify “new ways to treat or prevent the development of Parkinson’s disease, such as use of antidiabetes drugs to restore the brain’s insulin signaling,” said Dr. Warner. “A UCL-led study published last year found that a drug commonly used to treat diabetes shows promise in not only relieving Parkinson’s disease symptoms, but potentially altering the course of the disease itself. What we do not know is whether trying to treat people with type 2 diabetes better would reduce the risk of developing Parkinson’s disease.”

—Erik Greb

Suggested Reading

De Pablo-Fernandez E, Goldacre R, Pakpoor J, et al. Association between diabetes and subsequent Parkinson disease: a record-linkage cohort study. Neurology. 2018 Jun 13 [Epub ahead of print].

Compared with their white peers, black and Hispanic patients with intracerebral hemorrhage (ICH) have a higher risk of recurrence, according to data published online ahead of print June 6 in Neurology. Although black and Hispanic patients have more severe hypertension than whites do, severity of hypertension does not fully account for this increased risk. Future studies should examine whether novel biologic, socioeconomic, or cultural factors play a role, said the researchers.

The scientific literature indicates that blacks and Hispanics have a higher risk of first ICH than whites do. Alessandro Biffi, MD, head of the Aging and Brain Health Research group at Massachusetts General Hospital in Boston, and colleagues hypothesized that hypertension among these populations might contribute toward this increased risk. Because the subject had not been explored previously, Dr. Biffi and colleagues investigated the role of blood pressure and its variability in determining the risk of recurrent ICH among nonwhites.

An Analysis of Two Studies

The authors examined data from a longitudinal study of ICH conducted by Massachusetts General Hospital and from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study. They included patients who were 18 or older with a diagnosis of acute primary ICH in their analysis.

At enrollment, participants reported their race or ethnicity during a structured interview and underwent blood pressure measurement. The investigators performed follow-up through phone calls and reviews of medical records. Every six months, investigators recorded at least one blood-pressure measurement and quantified blood-pressure variability. Dr. Biffi and colleagues used Cox regression survival analysis to identify risk factors for ICH recurrence.

Systolic Blood Pressure Was Associated With Recurrence

Of the 2,291 patients included in the analysis, 1,121 were white, 529 were black, 605 were Hispanic, and 36 were of other race or ethnicity. The median systolic blood pressure during follow-up was 149 mm Hg for black participants, 146 mm Hg for Hispanic participants, and 141 mm Hg for white participants. Systolic blood pressure variability also was higher for black participants (median, 3.5%), compared with white participants (median, 2.8%).

In all, 26 (1.7%) white participants had ICH recurrence, compared with 35 (6.6%) black participants and 37 (6.1%) Hispanic participants. In univariable analyses, higher systolic blood pressure and greater systolic blood pressure variability were associated with increased ICH recurrence risk. Diastolic blood pressure and diastolic blood pressure variability, however, were not associated with ICH recurrence risk.

In multivariable analyses, black and Hispanic race or ethnicity remained independently associated with increased ICH recurrence risk in both studies, even after adjustment for systolic blood pressure and systolic blood pressure variability. Exposure to antihypertensive agents during follow-up was not associated with ICH recurrence and did not affect the results significantly. The associations were consistent in both studies.

Suggested Reading

Rodriguez-Torres A, Murphy M, Kourkoulis C, et al. Hypertension and intracerebral hemorrhage recurrence among white, black, and Hispanic individuals. Neurology. 2018 Jun 6 [Epub ahead of print].

Compared with their white peers, black and Hispanic patients with intracerebral hemorrhage (ICH) have a higher risk of recurrence, according to data published online ahead of print June 6 in Neurology. Although black and Hispanic patients have more severe hypertension than whites do, severity of hypertension does not fully account for this increased risk. Future studies should examine whether novel biologic, socioeconomic, or cultural factors play a role, said the researchers.

The scientific literature indicates that blacks and Hispanics have a higher risk of first ICH than whites do. Alessandro Biffi, MD, head of the Aging and Brain Health Research group at Massachusetts General Hospital in Boston, and colleagues hypothesized that hypertension among these populations might contribute toward this increased risk. Because the subject had not been explored previously, Dr. Biffi and colleagues investigated the role of blood pressure and its variability in determining the risk of recurrent ICH among nonwhites.

An Analysis of Two Studies

The authors examined data from a longitudinal study of ICH conducted by Massachusetts General Hospital and from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study. They included patients who were 18 or older with a diagnosis of acute primary ICH in their analysis.

At enrollment, participants reported their race or ethnicity during a structured interview and underwent blood pressure measurement. The investigators performed follow-up through phone calls and reviews of medical records. Every six months, investigators recorded at least one blood-pressure measurement and quantified blood-pressure variability. Dr. Biffi and colleagues used Cox regression survival analysis to identify risk factors for ICH recurrence.

Systolic Blood Pressure Was Associated With Recurrence

Of the 2,291 patients included in the analysis, 1,121 were white, 529 were black, 605 were Hispanic, and 36 were of other race or ethnicity. The median systolic blood pressure during follow-up was 149 mm Hg for black participants, 146 mm Hg for Hispanic participants, and 141 mm Hg for white participants. Systolic blood pressure variability also was higher for black participants (median, 3.5%), compared with white participants (median, 2.8%).

In all, 26 (1.7%) white participants had ICH recurrence, compared with 35 (6.6%) black participants and 37 (6.1%) Hispanic participants. In univariable analyses, higher systolic blood pressure and greater systolic blood pressure variability were associated with increased ICH recurrence risk. Diastolic blood pressure and diastolic blood pressure variability, however, were not associated with ICH recurrence risk.

In multivariable analyses, black and Hispanic race or ethnicity remained independently associated with increased ICH recurrence risk in both studies, even after adjustment for systolic blood pressure and systolic blood pressure variability. Exposure to antihypertensive agents during follow-up was not associated with ICH recurrence and did not affect the results significantly. The associations were consistent in both studies.

Suggested Reading

Rodriguez-Torres A, Murphy M, Kourkoulis C, et al. Hypertension and intracerebral hemorrhage recurrence among white, black, and Hispanic individuals. Neurology. 2018 Jun 6 [Epub ahead of print].

Compared with their white peers, black and Hispanic patients with intracerebral hemorrhage (ICH) have a higher risk of recurrence, according to data published online ahead of print June 6 in Neurology. Although black and Hispanic patients have more severe hypertension than whites do, severity of hypertension does not fully account for this increased risk. Future studies should examine whether novel biologic, socioeconomic, or cultural factors play a role, said the researchers.

The scientific literature indicates that blacks and Hispanics have a higher risk of first ICH than whites do. Alessandro Biffi, MD, head of the Aging and Brain Health Research group at Massachusetts General Hospital in Boston, and colleagues hypothesized that hypertension among these populations might contribute toward this increased risk. Because the subject had not been explored previously, Dr. Biffi and colleagues investigated the role of blood pressure and its variability in determining the risk of recurrent ICH among nonwhites.

An Analysis of Two Studies

The authors examined data from a longitudinal study of ICH conducted by Massachusetts General Hospital and from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study. They included patients who were 18 or older with a diagnosis of acute primary ICH in their analysis.

At enrollment, participants reported their race or ethnicity during a structured interview and underwent blood pressure measurement. The investigators performed follow-up through phone calls and reviews of medical records. Every six months, investigators recorded at least one blood-pressure measurement and quantified blood-pressure variability. Dr. Biffi and colleagues used Cox regression survival analysis to identify risk factors for ICH recurrence.

Systolic Blood Pressure Was Associated With Recurrence

Of the 2,291 patients included in the analysis, 1,121 were white, 529 were black, 605 were Hispanic, and 36 were of other race or ethnicity. The median systolic blood pressure during follow-up was 149 mm Hg for black participants, 146 mm Hg for Hispanic participants, and 141 mm Hg for white participants. Systolic blood pressure variability also was higher for black participants (median, 3.5%), compared with white participants (median, 2.8%).

In all, 26 (1.7%) white participants had ICH recurrence, compared with 35 (6.6%) black participants and 37 (6.1%) Hispanic participants. In univariable analyses, higher systolic blood pressure and greater systolic blood pressure variability were associated with increased ICH recurrence risk. Diastolic blood pressure and diastolic blood pressure variability, however, were not associated with ICH recurrence risk.

In multivariable analyses, black and Hispanic race or ethnicity remained independently associated with increased ICH recurrence risk in both studies, even after adjustment for systolic blood pressure and systolic blood pressure variability. Exposure to antihypertensive agents during follow-up was not associated with ICH recurrence and did not affect the results significantly. The associations were consistent in both studies.

Suggested Reading

Rodriguez-Torres A, Murphy M, Kourkoulis C, et al. Hypertension and intracerebral hemorrhage recurrence among white, black, and Hispanic individuals. Neurology. 2018 Jun 6 [Epub ahead of print].

Younger age of exposure to tackle football is not associated with chronic traumatic encephalopathy (CTE) pathologic severity, Alzheimer’s disease pathology, or Lewy body pathology, according to data published online ahead of print April 30 in Annals of Neurology. Younger age of exposure does appear to predict earlier neurobehavioral symptom onset, however, the authors said.

“These findings suggest that exposure to repetitive head impacts from tackle football as a youth may reduce resiliency to diseases, including, but not limited to, CTE, that affect the brain in later life,” said Michael L. Alosco, PhD, Assistant Professor of Neurology at the the Boston University Alzheimer’s Disease and CTE Center. “This study adds to growing research suggesting that incurring repeated head impacts through tackle football in earlier life can lead to both short-term and long-term effects on the brain.”

Repetitive Head Impacts and Neurodevelopment

Previous research has linked younger age of first exposure to tackle football with smaller thalamic volume in former National Football League players. A recent study of 214 former and amateur football players found that age of first exposure to tackle football—before age 12, in particular—predicted increased odds of self-reported neuropsychiatric and executive impairment.

“Youth exposure to repetitive head impacts may disrupt neurodevelopment to lower the threshold for later clinical dysfunction,” said the researchers.

To examine the effect of age of first exposure to tackle football on CTE pathologic severity and age of neurobehavioral symptom onset in tackle football players with neuropathologically confirmed CTE, Dr. Alosco and colleagues analyzed a sample of 246 amateur and professional tackle football players whose brains had been donated to the Veteran’s Affairs–Boston University–Concussion Legacy Foundation Brain Bank. The researchers interviewed informants to ascertain players’ age of first exposure and age of onset of cognitive, behavioral, or mood symptoms. A total of 211 football players were diagnosed with CTE; 35 did not have CTE. Of the 211 participants with CTE, 126 had CTE only, and the other participants had comorbid neurodegenerative diseases.

Onset of Cognitive, Behavioral, and Mood Symptoms

Of the 211 participants with CTE, 183 developed cognitive and behavioral or mood symptoms prior to death, eight had only cognitive symptoms, 12 had only behavioral or mood symptoms, and seven did not endorse any symptoms examined in the study. Clinical data for one participant were not available.

Among tackle football players with CTE, every one year younger that they began to play tackle football predicted earlier onset of cognitive symptoms by 2.44 years and of behavioral or mood symptoms by 2.50 years. Exposure before age 12 predicted earlier cognitive and behavioral or mood symptom onset by 13.39 years and 13.28 years, respectively.

Secondary subset analyses indicated that younger age of exposure to tackle football was associated with earlier onset of functional impairment in participants who were determined to have had dementia. Researchers observed nearly identical effects in participants with CTE only.

Study limitations include the lack of an appropriate control or comparison group, the researchers noted. In addition, the results may not be generalizable to a broader tackle football population.

“Given the growing public health concerns for participation in tackle football, prospective studies of former tackle football players that include objective clinical assessments are needed to better understand the relationship between youth tackle football exposure and long-term neurobehavioral outcomes,” said the researchers.

“More research on this topic is needed before any clinical recommendations, as well as recommendations on policy or rule changes, can be made,” said Dr. Alosco.

“Boston University and sites across the country are currently conducting longitudinal studies on former football players, which will allow us to begin to study cognition and behavior and mood functioning over time.”

—Erica Tricarico

Suggested Reading

Alosco ML, Mez J, Tripodis Y, et al. Age of first exposure to tackle football and chronic traumatic encephalopathy. Ann Neurol. 2018 Apr 30 [Epub ahead of print].

Younger age of exposure to tackle football is not associated with chronic traumatic encephalopathy (CTE) pathologic severity, Alzheimer’s disease pathology, or Lewy body pathology, according to data published online ahead of print April 30 in Annals of Neurology. Younger age of exposure does appear to predict earlier neurobehavioral symptom onset, however, the authors said.

“These findings suggest that exposure to repetitive head impacts from tackle football as a youth may reduce resiliency to diseases, including, but not limited to, CTE, that affect the brain in later life,” said Michael L. Alosco, PhD, Assistant Professor of Neurology at the the Boston University Alzheimer’s Disease and CTE Center. “This study adds to growing research suggesting that incurring repeated head impacts through tackle football in earlier life can lead to both short-term and long-term effects on the brain.”

Repetitive Head Impacts and Neurodevelopment

Previous research has linked younger age of first exposure to tackle football with smaller thalamic volume in former National Football League players. A recent study of 214 former and amateur football players found that age of first exposure to tackle football—before age 12, in particular—predicted increased odds of self-reported neuropsychiatric and executive impairment.

“Youth exposure to repetitive head impacts may disrupt neurodevelopment to lower the threshold for later clinical dysfunction,” said the researchers.

To examine the effect of age of first exposure to tackle football on CTE pathologic severity and age of neurobehavioral symptom onset in tackle football players with neuropathologically confirmed CTE, Dr. Alosco and colleagues analyzed a sample of 246 amateur and professional tackle football players whose brains had been donated to the Veteran’s Affairs–Boston University–Concussion Legacy Foundation Brain Bank. The researchers interviewed informants to ascertain players’ age of first exposure and age of onset of cognitive, behavioral, or mood symptoms. A total of 211 football players were diagnosed with CTE; 35 did not have CTE. Of the 211 participants with CTE, 126 had CTE only, and the other participants had comorbid neurodegenerative diseases.

Onset of Cognitive, Behavioral, and Mood Symptoms

Of the 211 participants with CTE, 183 developed cognitive and behavioral or mood symptoms prior to death, eight had only cognitive symptoms, 12 had only behavioral or mood symptoms, and seven did not endorse any symptoms examined in the study. Clinical data for one participant were not available.

Among tackle football players with CTE, every one year younger that they began to play tackle football predicted earlier onset of cognitive symptoms by 2.44 years and of behavioral or mood symptoms by 2.50 years. Exposure before age 12 predicted earlier cognitive and behavioral or mood symptom onset by 13.39 years and 13.28 years, respectively.

Secondary subset analyses indicated that younger age of exposure to tackle football was associated with earlier onset of functional impairment in participants who were determined to have had dementia. Researchers observed nearly identical effects in participants with CTE only.

Study limitations include the lack of an appropriate control or comparison group, the researchers noted. In addition, the results may not be generalizable to a broader tackle football population.

“Given the growing public health concerns for participation in tackle football, prospective studies of former tackle football players that include objective clinical assessments are needed to better understand the relationship between youth tackle football exposure and long-term neurobehavioral outcomes,” said the researchers.

“More research on this topic is needed before any clinical recommendations, as well as recommendations on policy or rule changes, can be made,” said Dr. Alosco.

“Boston University and sites across the country are currently conducting longitudinal studies on former football players, which will allow us to begin to study cognition and behavior and mood functioning over time.”

—Erica Tricarico

Suggested Reading

Alosco ML, Mez J, Tripodis Y, et al. Age of first exposure to tackle football and chronic traumatic encephalopathy. Ann Neurol. 2018 Apr 30 [Epub ahead of print].

Younger age of exposure to tackle football is not associated with chronic traumatic encephalopathy (CTE) pathologic severity, Alzheimer’s disease pathology, or Lewy body pathology, according to data published online ahead of print April 30 in Annals of Neurology. Younger age of exposure does appear to predict earlier neurobehavioral symptom onset, however, the authors said.

“These findings suggest that exposure to repetitive head impacts from tackle football as a youth may reduce resiliency to diseases, including, but not limited to, CTE, that affect the brain in later life,” said Michael L. Alosco, PhD, Assistant Professor of Neurology at the the Boston University Alzheimer’s Disease and CTE Center. “This study adds to growing research suggesting that incurring repeated head impacts through tackle football in earlier life can lead to both short-term and long-term effects on the brain.”

Repetitive Head Impacts and Neurodevelopment

Previous research has linked younger age of first exposure to tackle football with smaller thalamic volume in former National Football League players. A recent study of 214 former and amateur football players found that age of first exposure to tackle football—before age 12, in particular—predicted increased odds of self-reported neuropsychiatric and executive impairment.

“Youth exposure to repetitive head impacts may disrupt neurodevelopment to lower the threshold for later clinical dysfunction,” said the researchers.

To examine the effect of age of first exposure to tackle football on CTE pathologic severity and age of neurobehavioral symptom onset in tackle football players with neuropathologically confirmed CTE, Dr. Alosco and colleagues analyzed a sample of 246 amateur and professional tackle football players whose brains had been donated to the Veteran’s Affairs–Boston University–Concussion Legacy Foundation Brain Bank. The researchers interviewed informants to ascertain players’ age of first exposure and age of onset of cognitive, behavioral, or mood symptoms. A total of 211 football players were diagnosed with CTE; 35 did not have CTE. Of the 211 participants with CTE, 126 had CTE only, and the other participants had comorbid neurodegenerative diseases.

Onset of Cognitive, Behavioral, and Mood Symptoms

Of the 211 participants with CTE, 183 developed cognitive and behavioral or mood symptoms prior to death, eight had only cognitive symptoms, 12 had only behavioral or mood symptoms, and seven did not endorse any symptoms examined in the study. Clinical data for one participant were not available.

Among tackle football players with CTE, every one year younger that they began to play tackle football predicted earlier onset of cognitive symptoms by 2.44 years and of behavioral or mood symptoms by 2.50 years. Exposure before age 12 predicted earlier cognitive and behavioral or mood symptom onset by 13.39 years and 13.28 years, respectively.

Secondary subset analyses indicated that younger age of exposure to tackle football was associated with earlier onset of functional impairment in participants who were determined to have had dementia. Researchers observed nearly identical effects in participants with CTE only.

Study limitations include the lack of an appropriate control or comparison group, the researchers noted. In addition, the results may not be generalizable to a broader tackle football population.

“Given the growing public health concerns for participation in tackle football, prospective studies of former tackle football players that include objective clinical assessments are needed to better understand the relationship between youth tackle football exposure and long-term neurobehavioral outcomes,” said the researchers.

“More research on this topic is needed before any clinical recommendations, as well as recommendations on policy or rule changes, can be made,” said Dr. Alosco.

“Boston University and sites across the country are currently conducting longitudinal studies on former football players, which will allow us to begin to study cognition and behavior and mood functioning over time.”

—Erica Tricarico

Suggested Reading

Alosco ML, Mez J, Tripodis Y, et al. Age of first exposure to tackle football and chronic traumatic encephalopathy. Ann Neurol. 2018 Apr 30 [Epub ahead of print].

The accumulation of phosphorylated α-synuclein in the retina may serve as a biomarker of brain pathology severity and aid in diagnosis and monitoring of Parkinson’s disease, according to data published online ahead of print May 8 in Movement Disorders.

“These data suggest that phosphorylated α-synuclein accumulates in the retina in parallel with that in the brain, including in early stages preceding development of clinical signs of parkinsonism or dementia,” said Nicolás Cuenca, PhD, Assistant Professor of Physiology, Genetics, and Microbiology at the University of Alicante in Spain, and colleagues.

—Erica Tricarico

Suggested Reading

Ortuño-Lizarán I, Beach TG, Serrano GE, et al. Phosphorylated α-synuclein in the retina is a biomarker of Parkinson’s disease pathology severity. Mov Disord. 2018 May 8 [Epub ahead of print].

Ma LJ, Xu LL, Mao CJ, et al. Progressive changes in the retinal structure of patients with Parkinson’s disease. J Parkinsons Dis. 2018;8(1):85-92.

The accumulation of phosphorylated α-synuclein in the retina may serve as a biomarker of brain pathology severity and aid in diagnosis and monitoring of Parkinson’s disease, according to data published online ahead of print May 8 in Movement Disorders.

“These data suggest that phosphorylated α-synuclein accumulates in the retina in parallel with that in the brain, including in early stages preceding development of clinical signs of parkinsonism or dementia,” said Nicolás Cuenca, PhD, Assistant Professor of Physiology, Genetics, and Microbiology at the University of Alicante in Spain, and colleagues.

—Erica Tricarico

Suggested Reading

Ortuño-Lizarán I, Beach TG, Serrano GE, et al. Phosphorylated α-synuclein in the retina is a biomarker of Parkinson’s disease pathology severity. Mov Disord. 2018 May 8 [Epub ahead of print].

Ma LJ, Xu LL, Mao CJ, et al. Progressive changes in the retinal structure of patients with Parkinson’s disease. J Parkinsons Dis. 2018;8(1):85-92.

The accumulation of phosphorylated α-synuclein in the retina may serve as a biomarker of brain pathology severity and aid in diagnosis and monitoring of Parkinson’s disease, according to data published online ahead of print May 8 in Movement Disorders.

“These data suggest that phosphorylated α-synuclein accumulates in the retina in parallel with that in the brain, including in early stages preceding development of clinical signs of parkinsonism or dementia,” said Nicolás Cuenca, PhD, Assistant Professor of Physiology, Genetics, and Microbiology at the University of Alicante in Spain, and colleagues.

—Erica Tricarico

Suggested Reading

Ortuño-Lizarán I, Beach TG, Serrano GE, et al. Phosphorylated α-synuclein in the retina is a biomarker of Parkinson’s disease pathology severity. Mov Disord. 2018 May 8 [Epub ahead of print].

Ma LJ, Xu LL, Mao CJ, et al. Progressive changes in the retinal structure of patients with Parkinson’s disease. J Parkinsons Dis. 2018;8(1):85-92.