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Does TBI in Later Life Increase the Risk for Parkinson’s Disease?
Patients 55 and older who present to inpatient and emergency department settings with a traumatic brain injury (TBI) have a 44% increased risk of developing Parkinson’s disease over five to seven years, compared with patients in the same age group who present with non-TBI trauma (NTT), according to research published online ahead of print February 27 in Annals of Neurology. In addition, the risk of developing Parkinson’s disease doubles following more severe or more frequent TBI, compared with mild or single TBI. This finding supports a causal association between TBI and Parkinson’s disease.
Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues analyzed International Classification of Diseases, Ninth Revision code data collected at California hospitals from 2005 to 2006 to evaluate the risk of developing Parkinson’s disease after TBI in older adulthood. Because of the theoretical possibility that patients with incipient Parkinson’s disease are more likely to fall and sustain a TBI than healthy controls, the researchers examined patients with NTT—defined as fracture, excluding fractures of the head and neck—to reduce possible confounding and reverse causation. To reduce the chance of reverse causation further, researchers excluded cases in which Parkinson’s disease was diagnosed less than a year after the injury.
Researchers identified 52,393 patients with TBI and 113,406 patients with NTT who survived hospitalization and did not have Parkinson’s disease or dementia at baseline. Using Kaplan–Meier estimates and Cox proportional hazards models adjusted for age, sex, race or ethnicity, income, comorbidities, health care use, and trauma severity, they estimated the risk of Parkinson’s disease after TBI during follow-up ending in 2011.
Patients With TBI Were Diagnosed Sooner
Patients with TBI were significantly more likely to be diagnosed with Parkinson’s disease, compared with NTT patients (1.7% of patients vs 1.1% of patients), and patients with TBI were diagnosed with Parkinson’s disease slightly sooner than those with NTT (at 3.1 years, compared with 3.3 years). Researchers found that risk of Parkinson’s disease was similar for TBI sustained via falls and for TBI sustained through other mechanisms.
Researchers also assessed the effect of TBI severity and TBI frequency and found a significant dose response. Patients with mild TBI were 24% more likely to develop Parkinson’s disease, and patients with moderate to severe TBI were 50% more likely to develop Parkinson’s disease, compared with those with NTT. “The evidence for a dose response for increasing TBI severity and TBI frequency, and our persistently significant results despite multiple additional analyses, all enhance causal inference,” the authors said.
A causal association between TBI and Parkinson’s disease may be explained by several possible mechanisms, the researchers said. TBI may reduce motor reserve, thus leading to an earlier diagnosis of Parkinson’s disease in susceptible patients. TBI also may accelerate or augment a pre-existing neurodegenerative cascade or trigger a de novo neurodegenerative cascade. The question of whether typical Parkinson’s disease neuropathologies or unique TBI-specific neuropathology causes post-TBI syndromes deserves further study, they said.
Studies using animal models support a causal mechanism for post-TBI Parkinson’s disease. For example, a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the substantia nigra have been found in rats after experimentally induced TBI. Other research has begun to replicate these findings in humans.
Information About Patients Was Limited
The study’s limitations include the use of administrative diagnostic codes, which may be poorly sensitive or specific to Parkinson’s disease diagnoses. The researchers lacked information regarding patients’ medical histories and other data about patients’ treatments and outcomes. Also, post-traumatic motor or behavioral abnormalities may complicate the diagnosis of Parkinson’s disease, and diagnoses were not verified by expert review. In addition, the use of a trauma control group essentially controlled for any additional harmful effects of trauma on the nervous system that potentially could increase risk of Parkinson’s disease independently. It is important for large-scale prospective studies, ideally with autopsy confirmation, to confirm these findings, the investigators said.
The results are in line with a 2013 meta-analysis of 22 studies that reported a pooled odds ratio of 1.57 for the association between Parkinson’s disease and head trauma, the authors said. When considered with other studies, including prior research by Dr. Gardner’s team that identified a 26% increased risk of dementia after TBI versus NTT in this population, the results “suggest that TBI is an important independent risk factor for a variety of neurodegenerative syndromes.”
The findings also highlight the importance of preventing falls, which caused approximately 66% of trauma in the TBI and NTT groups. “As the cause of trauma in this study was overwhelmingly due to falls, there is critical importance for fall prevention in middle-aged and older adults, not only as a means to prevent bodily injury, but potentially as a means to prevent neurodegenerative diseases such as dementia and Parkinson’s disease,” the authors concluded.
Suggested Reading
Gardner RC, Burke JF, Nettiksimmons J, et al. Traumatic brain injury in later life increases risk for Parkinson’s disease. Ann Neurol. 2015 Feb 27 [Epub ahead of print].
Jafari S, Etminan M, Aminzadeh F, Samii A. Head injury and risk of Parkinson disease: a systematic review and meta-analysis. Mov Disord. 2013;28(9):1222-1229.
Patients 55 and older who present to inpatient and emergency department settings with a traumatic brain injury (TBI) have a 44% increased risk of developing Parkinson’s disease over five to seven years, compared with patients in the same age group who present with non-TBI trauma (NTT), according to research published online ahead of print February 27 in Annals of Neurology. In addition, the risk of developing Parkinson’s disease doubles following more severe or more frequent TBI, compared with mild or single TBI. This finding supports a causal association between TBI and Parkinson’s disease.
Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues analyzed International Classification of Diseases, Ninth Revision code data collected at California hospitals from 2005 to 2006 to evaluate the risk of developing Parkinson’s disease after TBI in older adulthood. Because of the theoretical possibility that patients with incipient Parkinson’s disease are more likely to fall and sustain a TBI than healthy controls, the researchers examined patients with NTT—defined as fracture, excluding fractures of the head and neck—to reduce possible confounding and reverse causation. To reduce the chance of reverse causation further, researchers excluded cases in which Parkinson’s disease was diagnosed less than a year after the injury.
Researchers identified 52,393 patients with TBI and 113,406 patients with NTT who survived hospitalization and did not have Parkinson’s disease or dementia at baseline. Using Kaplan–Meier estimates and Cox proportional hazards models adjusted for age, sex, race or ethnicity, income, comorbidities, health care use, and trauma severity, they estimated the risk of Parkinson’s disease after TBI during follow-up ending in 2011.
Patients With TBI Were Diagnosed Sooner
Patients with TBI were significantly more likely to be diagnosed with Parkinson’s disease, compared with NTT patients (1.7% of patients vs 1.1% of patients), and patients with TBI were diagnosed with Parkinson’s disease slightly sooner than those with NTT (at 3.1 years, compared with 3.3 years). Researchers found that risk of Parkinson’s disease was similar for TBI sustained via falls and for TBI sustained through other mechanisms.
Researchers also assessed the effect of TBI severity and TBI frequency and found a significant dose response. Patients with mild TBI were 24% more likely to develop Parkinson’s disease, and patients with moderate to severe TBI were 50% more likely to develop Parkinson’s disease, compared with those with NTT. “The evidence for a dose response for increasing TBI severity and TBI frequency, and our persistently significant results despite multiple additional analyses, all enhance causal inference,” the authors said.
A causal association between TBI and Parkinson’s disease may be explained by several possible mechanisms, the researchers said. TBI may reduce motor reserve, thus leading to an earlier diagnosis of Parkinson’s disease in susceptible patients. TBI also may accelerate or augment a pre-existing neurodegenerative cascade or trigger a de novo neurodegenerative cascade. The question of whether typical Parkinson’s disease neuropathologies or unique TBI-specific neuropathology causes post-TBI syndromes deserves further study, they said.
Studies using animal models support a causal mechanism for post-TBI Parkinson’s disease. For example, a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the substantia nigra have been found in rats after experimentally induced TBI. Other research has begun to replicate these findings in humans.
Information About Patients Was Limited
The study’s limitations include the use of administrative diagnostic codes, which may be poorly sensitive or specific to Parkinson’s disease diagnoses. The researchers lacked information regarding patients’ medical histories and other data about patients’ treatments and outcomes. Also, post-traumatic motor or behavioral abnormalities may complicate the diagnosis of Parkinson’s disease, and diagnoses were not verified by expert review. In addition, the use of a trauma control group essentially controlled for any additional harmful effects of trauma on the nervous system that potentially could increase risk of Parkinson’s disease independently. It is important for large-scale prospective studies, ideally with autopsy confirmation, to confirm these findings, the investigators said.
The results are in line with a 2013 meta-analysis of 22 studies that reported a pooled odds ratio of 1.57 for the association between Parkinson’s disease and head trauma, the authors said. When considered with other studies, including prior research by Dr. Gardner’s team that identified a 26% increased risk of dementia after TBI versus NTT in this population, the results “suggest that TBI is an important independent risk factor for a variety of neurodegenerative syndromes.”
The findings also highlight the importance of preventing falls, which caused approximately 66% of trauma in the TBI and NTT groups. “As the cause of trauma in this study was overwhelmingly due to falls, there is critical importance for fall prevention in middle-aged and older adults, not only as a means to prevent bodily injury, but potentially as a means to prevent neurodegenerative diseases such as dementia and Parkinson’s disease,” the authors concluded.
Patients 55 and older who present to inpatient and emergency department settings with a traumatic brain injury (TBI) have a 44% increased risk of developing Parkinson’s disease over five to seven years, compared with patients in the same age group who present with non-TBI trauma (NTT), according to research published online ahead of print February 27 in Annals of Neurology. In addition, the risk of developing Parkinson’s disease doubles following more severe or more frequent TBI, compared with mild or single TBI. This finding supports a causal association between TBI and Parkinson’s disease.
Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues analyzed International Classification of Diseases, Ninth Revision code data collected at California hospitals from 2005 to 2006 to evaluate the risk of developing Parkinson’s disease after TBI in older adulthood. Because of the theoretical possibility that patients with incipient Parkinson’s disease are more likely to fall and sustain a TBI than healthy controls, the researchers examined patients with NTT—defined as fracture, excluding fractures of the head and neck—to reduce possible confounding and reverse causation. To reduce the chance of reverse causation further, researchers excluded cases in which Parkinson’s disease was diagnosed less than a year after the injury.
Researchers identified 52,393 patients with TBI and 113,406 patients with NTT who survived hospitalization and did not have Parkinson’s disease or dementia at baseline. Using Kaplan–Meier estimates and Cox proportional hazards models adjusted for age, sex, race or ethnicity, income, comorbidities, health care use, and trauma severity, they estimated the risk of Parkinson’s disease after TBI during follow-up ending in 2011.
Patients With TBI Were Diagnosed Sooner
Patients with TBI were significantly more likely to be diagnosed with Parkinson’s disease, compared with NTT patients (1.7% of patients vs 1.1% of patients), and patients with TBI were diagnosed with Parkinson’s disease slightly sooner than those with NTT (at 3.1 years, compared with 3.3 years). Researchers found that risk of Parkinson’s disease was similar for TBI sustained via falls and for TBI sustained through other mechanisms.
Researchers also assessed the effect of TBI severity and TBI frequency and found a significant dose response. Patients with mild TBI were 24% more likely to develop Parkinson’s disease, and patients with moderate to severe TBI were 50% more likely to develop Parkinson’s disease, compared with those with NTT. “The evidence for a dose response for increasing TBI severity and TBI frequency, and our persistently significant results despite multiple additional analyses, all enhance causal inference,” the authors said.
A causal association between TBI and Parkinson’s disease may be explained by several possible mechanisms, the researchers said. TBI may reduce motor reserve, thus leading to an earlier diagnosis of Parkinson’s disease in susceptible patients. TBI also may accelerate or augment a pre-existing neurodegenerative cascade or trigger a de novo neurodegenerative cascade. The question of whether typical Parkinson’s disease neuropathologies or unique TBI-specific neuropathology causes post-TBI syndromes deserves further study, they said.
Studies using animal models support a causal mechanism for post-TBI Parkinson’s disease. For example, a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the substantia nigra have been found in rats after experimentally induced TBI. Other research has begun to replicate these findings in humans.
Information About Patients Was Limited
The study’s limitations include the use of administrative diagnostic codes, which may be poorly sensitive or specific to Parkinson’s disease diagnoses. The researchers lacked information regarding patients’ medical histories and other data about patients’ treatments and outcomes. Also, post-traumatic motor or behavioral abnormalities may complicate the diagnosis of Parkinson’s disease, and diagnoses were not verified by expert review. In addition, the use of a trauma control group essentially controlled for any additional harmful effects of trauma on the nervous system that potentially could increase risk of Parkinson’s disease independently. It is important for large-scale prospective studies, ideally with autopsy confirmation, to confirm these findings, the investigators said.
The results are in line with a 2013 meta-analysis of 22 studies that reported a pooled odds ratio of 1.57 for the association between Parkinson’s disease and head trauma, the authors said. When considered with other studies, including prior research by Dr. Gardner’s team that identified a 26% increased risk of dementia after TBI versus NTT in this population, the results “suggest that TBI is an important independent risk factor for a variety of neurodegenerative syndromes.”
The findings also highlight the importance of preventing falls, which caused approximately 66% of trauma in the TBI and NTT groups. “As the cause of trauma in this study was overwhelmingly due to falls, there is critical importance for fall prevention in middle-aged and older adults, not only as a means to prevent bodily injury, but potentially as a means to prevent neurodegenerative diseases such as dementia and Parkinson’s disease,” the authors concluded.
Suggested Reading
Gardner RC, Burke JF, Nettiksimmons J, et al. Traumatic brain injury in later life increases risk for Parkinson’s disease. Ann Neurol. 2015 Feb 27 [Epub ahead of print].
Jafari S, Etminan M, Aminzadeh F, Samii A. Head injury and risk of Parkinson disease: a systematic review and meta-analysis. Mov Disord. 2013;28(9):1222-1229.
Suggested Reading
Gardner RC, Burke JF, Nettiksimmons J, et al. Traumatic brain injury in later life increases risk for Parkinson’s disease. Ann Neurol. 2015 Feb 27 [Epub ahead of print].
Jafari S, Etminan M, Aminzadeh F, Samii A. Head injury and risk of Parkinson disease: a systematic review and meta-analysis. Mov Disord. 2013;28(9):1222-1229.
AAN/AES Guideline on Management of Unprovoked First Seizure in Adults
The Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society addressed seizure recurrence, immediate treatment with antiepileptic drugs (AEDs), and adverse events (AEs) related to AEDs in patients with an unprovoked first seizure. The risk of recurrence after an unprovoked first seizure is greatest within the first 2 years, especially in the first year. Immediate AED therapy after an unprovoked first seizure reduces the risk of seizure recurrence by approximately 35% within the subsequent 2 years; however, immediate treatment with AED is unlikely to improve sustained seizure remission over the longer term (>3 years). Adverse events associated with the immediate treatment of unprovoked first seizure with AEDs are predominantly mild and reversible, occurring in about 7% to 31% of patients.
Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology. 2015;84(16):1705-1713.
The Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society addressed seizure recurrence, immediate treatment with antiepileptic drugs (AEDs), and adverse events (AEs) related to AEDs in patients with an unprovoked first seizure. The risk of recurrence after an unprovoked first seizure is greatest within the first 2 years, especially in the first year. Immediate AED therapy after an unprovoked first seizure reduces the risk of seizure recurrence by approximately 35% within the subsequent 2 years; however, immediate treatment with AED is unlikely to improve sustained seizure remission over the longer term (>3 years). Adverse events associated with the immediate treatment of unprovoked first seizure with AEDs are predominantly mild and reversible, occurring in about 7% to 31% of patients.
Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology. 2015;84(16):1705-1713.
The Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society addressed seizure recurrence, immediate treatment with antiepileptic drugs (AEDs), and adverse events (AEs) related to AEDs in patients with an unprovoked first seizure. The risk of recurrence after an unprovoked first seizure is greatest within the first 2 years, especially in the first year. Immediate AED therapy after an unprovoked first seizure reduces the risk of seizure recurrence by approximately 35% within the subsequent 2 years; however, immediate treatment with AED is unlikely to improve sustained seizure remission over the longer term (>3 years). Adverse events associated with the immediate treatment of unprovoked first seizure with AEDs are predominantly mild and reversible, occurring in about 7% to 31% of patients.
Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology. 2015;84(16):1705-1713.
New Guideline Offers Advice for First Unprovoked Seizure
WASHINGTON, DC—A new guideline found that administering an antiepileptic drug (AED) immediately after a first seizure reduces the risk of another seizure within two years. Announced at the 67th Annual Meeting of the American Academy of Neurology and published in the April 21 issue of Neurology, the evidence-based guideline was developed jointly by the American Academy of Neurology and the American Epilepsy Society.
“Determining whether to treat a patient after a first seizure is a complex process, but this guideline supports the use of medication in some cases and could influence standard practice for many physicians,” said lead author Allan Krumholz, MD, Professor of Neurology at the University of Maryland School of Medicine in Baltimore. “A single seizure could be a sign of epilepsy. Even one seizure is traumatic and can affect many aspects of an individual’s life from driving a car to employment options. This guideline clarifies when a person’s risk for another seizure warrants medication.”
One in 10 people worldwide have a first seizure in their lifetime. Annually, about 150,000 adults in the United States have an unprovoked seizure. In addition, one in 26 Americans will develop epilepsy. According to the International League Against Epilepsy, epilepsy is defined as one or more seizures with a high likelihood of recurrence, not due to another immediately triggering cause, such as low blood sugar.
The guideline authors reviewed nearly 50 studies on first seizure that addressed the probability that an adult with an unprovoked first seizure would have recurrent seizures, in addition to information about short- and long-term health risks and medication side effects.
The authors found strong evidence that for adults who have had a first seizure, the risk of another seizure is greatest within the first two years. The risk ranges from about a one-in-five chance (21%) to nearly a one-in-two chance (45%). They also found strong evidence that the risk of another seizure is greatest in those with a previous brain injury such as a stroke, brain tumor, or head trauma and in those with an EEG test result that shows signs of epilepsy. Their analysis revealed moderate evidence that the risk is greatest in people with a significant abnormality on brain imaging and in those who have nocturnal seizures.
According to the guideline, there is moderate evidence to suggest that immediate treatment with an AED lowers the risk of another seizure by 35% within the first two years. “About half of patients who have a first seizure will never have another seizure, but for the other half, immediate drug therapy may help,” Dr. Krumholz said. He stressed that the guideline should be used by physicians to help inform patients of their individual risk of a second seizure and involve them in the decision-making process.
The guideline cites moderate evidence suggesting that while treatment was shown to provide a short-term benefit, over the longer term (more than three years), treating a first seizure immediately rather than waiting for another seizure to occur is unlikely to increase or decrease the likelihood of remaining seizure free.
The guideline notes that 7% to 31% of patients who take an AED will experience a drug side effect; however, these are usually mild and can be reversed when a patient is switched to another AED or the dose is lowered.
“This guideline does not give a simple, black-and-white recommendation [about] whether an adult should immediately be started on an epilepsy drug,” said coauthor Jacqueline French, MD, a Professor of Neurology and Director of Translational Research at New York University’s Langone Comprehensive Epilepsy Center in New York City. “What is most important is that the decision whether to immediately treat a first seizure requires meaningful conversation between patient and doctor so that the patient’s individual circumstances, balance of risks and benefits, and personal preferences are understood and accounted for.”
The guideline was endorsed by the American Neurological Association and the World Federation of Neurology.
Suggested Reading
Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology. 2015;84:1705-1713.
WASHINGTON, DC—A new guideline found that administering an antiepileptic drug (AED) immediately after a first seizure reduces the risk of another seizure within two years. Announced at the 67th Annual Meeting of the American Academy of Neurology and published in the April 21 issue of Neurology, the evidence-based guideline was developed jointly by the American Academy of Neurology and the American Epilepsy Society.
“Determining whether to treat a patient after a first seizure is a complex process, but this guideline supports the use of medication in some cases and could influence standard practice for many physicians,” said lead author Allan Krumholz, MD, Professor of Neurology at the University of Maryland School of Medicine in Baltimore. “A single seizure could be a sign of epilepsy. Even one seizure is traumatic and can affect many aspects of an individual’s life from driving a car to employment options. This guideline clarifies when a person’s risk for another seizure warrants medication.”
One in 10 people worldwide have a first seizure in their lifetime. Annually, about 150,000 adults in the United States have an unprovoked seizure. In addition, one in 26 Americans will develop epilepsy. According to the International League Against Epilepsy, epilepsy is defined as one or more seizures with a high likelihood of recurrence, not due to another immediately triggering cause, such as low blood sugar.
The guideline authors reviewed nearly 50 studies on first seizure that addressed the probability that an adult with an unprovoked first seizure would have recurrent seizures, in addition to information about short- and long-term health risks and medication side effects.
The authors found strong evidence that for adults who have had a first seizure, the risk of another seizure is greatest within the first two years. The risk ranges from about a one-in-five chance (21%) to nearly a one-in-two chance (45%). They also found strong evidence that the risk of another seizure is greatest in those with a previous brain injury such as a stroke, brain tumor, or head trauma and in those with an EEG test result that shows signs of epilepsy. Their analysis revealed moderate evidence that the risk is greatest in people with a significant abnormality on brain imaging and in those who have nocturnal seizures.
According to the guideline, there is moderate evidence to suggest that immediate treatment with an AED lowers the risk of another seizure by 35% within the first two years. “About half of patients who have a first seizure will never have another seizure, but for the other half, immediate drug therapy may help,” Dr. Krumholz said. He stressed that the guideline should be used by physicians to help inform patients of their individual risk of a second seizure and involve them in the decision-making process.
The guideline cites moderate evidence suggesting that while treatment was shown to provide a short-term benefit, over the longer term (more than three years), treating a first seizure immediately rather than waiting for another seizure to occur is unlikely to increase or decrease the likelihood of remaining seizure free.
The guideline notes that 7% to 31% of patients who take an AED will experience a drug side effect; however, these are usually mild and can be reversed when a patient is switched to another AED or the dose is lowered.
“This guideline does not give a simple, black-and-white recommendation [about] whether an adult should immediately be started on an epilepsy drug,” said coauthor Jacqueline French, MD, a Professor of Neurology and Director of Translational Research at New York University’s Langone Comprehensive Epilepsy Center in New York City. “What is most important is that the decision whether to immediately treat a first seizure requires meaningful conversation between patient and doctor so that the patient’s individual circumstances, balance of risks and benefits, and personal preferences are understood and accounted for.”
The guideline was endorsed by the American Neurological Association and the World Federation of Neurology.
WASHINGTON, DC—A new guideline found that administering an antiepileptic drug (AED) immediately after a first seizure reduces the risk of another seizure within two years. Announced at the 67th Annual Meeting of the American Academy of Neurology and published in the April 21 issue of Neurology, the evidence-based guideline was developed jointly by the American Academy of Neurology and the American Epilepsy Society.
“Determining whether to treat a patient after a first seizure is a complex process, but this guideline supports the use of medication in some cases and could influence standard practice for many physicians,” said lead author Allan Krumholz, MD, Professor of Neurology at the University of Maryland School of Medicine in Baltimore. “A single seizure could be a sign of epilepsy. Even one seizure is traumatic and can affect many aspects of an individual’s life from driving a car to employment options. This guideline clarifies when a person’s risk for another seizure warrants medication.”
One in 10 people worldwide have a first seizure in their lifetime. Annually, about 150,000 adults in the United States have an unprovoked seizure. In addition, one in 26 Americans will develop epilepsy. According to the International League Against Epilepsy, epilepsy is defined as one or more seizures with a high likelihood of recurrence, not due to another immediately triggering cause, such as low blood sugar.
The guideline authors reviewed nearly 50 studies on first seizure that addressed the probability that an adult with an unprovoked first seizure would have recurrent seizures, in addition to information about short- and long-term health risks and medication side effects.
The authors found strong evidence that for adults who have had a first seizure, the risk of another seizure is greatest within the first two years. The risk ranges from about a one-in-five chance (21%) to nearly a one-in-two chance (45%). They also found strong evidence that the risk of another seizure is greatest in those with a previous brain injury such as a stroke, brain tumor, or head trauma and in those with an EEG test result that shows signs of epilepsy. Their analysis revealed moderate evidence that the risk is greatest in people with a significant abnormality on brain imaging and in those who have nocturnal seizures.
According to the guideline, there is moderate evidence to suggest that immediate treatment with an AED lowers the risk of another seizure by 35% within the first two years. “About half of patients who have a first seizure will never have another seizure, but for the other half, immediate drug therapy may help,” Dr. Krumholz said. He stressed that the guideline should be used by physicians to help inform patients of their individual risk of a second seizure and involve them in the decision-making process.
The guideline cites moderate evidence suggesting that while treatment was shown to provide a short-term benefit, over the longer term (more than three years), treating a first seizure immediately rather than waiting for another seizure to occur is unlikely to increase or decrease the likelihood of remaining seizure free.
The guideline notes that 7% to 31% of patients who take an AED will experience a drug side effect; however, these are usually mild and can be reversed when a patient is switched to another AED or the dose is lowered.
“This guideline does not give a simple, black-and-white recommendation [about] whether an adult should immediately be started on an epilepsy drug,” said coauthor Jacqueline French, MD, a Professor of Neurology and Director of Translational Research at New York University’s Langone Comprehensive Epilepsy Center in New York City. “What is most important is that the decision whether to immediately treat a first seizure requires meaningful conversation between patient and doctor so that the patient’s individual circumstances, balance of risks and benefits, and personal preferences are understood and accounted for.”
The guideline was endorsed by the American Neurological Association and the World Federation of Neurology.
Suggested Reading
Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology. 2015;84:1705-1713.
Suggested Reading
Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology. 2015;84:1705-1713.
Does Deep Brain Stimulation of ANT Provide Sustained Efficacy and Safety?
Deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy showed sustained efficacy and safety in this long-term follow-up of the SANTE trial. This study shows that ANT stimulation was associated with seizure frequency reduction rate of 69% at 5 years. The study also reported that 16% of subjects were seizure-free for ≥6 months during the 5 years of follow-up. ANT stimulation was associated with a 34% serious device-related adverse event rate at 5 years.
Salanova V, Witt T, Worth R, et al; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug resistant partial epilepsy. Neurology. 2015;84(10):1017-1025.
Deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy showed sustained efficacy and safety in this long-term follow-up of the SANTE trial. This study shows that ANT stimulation was associated with seizure frequency reduction rate of 69% at 5 years. The study also reported that 16% of subjects were seizure-free for ≥6 months during the 5 years of follow-up. ANT stimulation was associated with a 34% serious device-related adverse event rate at 5 years.
Salanova V, Witt T, Worth R, et al; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug resistant partial epilepsy. Neurology. 2015;84(10):1017-1025.
Deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy showed sustained efficacy and safety in this long-term follow-up of the SANTE trial. This study shows that ANT stimulation was associated with seizure frequency reduction rate of 69% at 5 years. The study also reported that 16% of subjects were seizure-free for ≥6 months during the 5 years of follow-up. ANT stimulation was associated with a 34% serious device-related adverse event rate at 5 years.
Salanova V, Witt T, Worth R, et al; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug resistant partial epilepsy. Neurology. 2015;84(10):1017-1025.
Do Memory and Mood Affect AED Adherence?
In a cross-sectional study, one hundred patients with epilepsy on antiepileptic drug (AED) therapy were observed to determine adherence to treatment. Patients in the adherent group—65% of the population—were found to have significantly lower depression scores compared with the nonadherent group. Memory scores were not robustly correlated with adherence. The authors conclude that physicians should consider targeting patients with epilepsy and comorbid depression as they may be at a higher risk of nonadherence.
McAuley JW, Passen N, Prusa C, Dixon J, Cotterman-Hart S, Shneker BF. An evaluation of the impact of memory and mood on antiepileptic drug adherence. Epilepsy Behav. 2015;43:61-65.
In a cross-sectional study, one hundred patients with epilepsy on antiepileptic drug (AED) therapy were observed to determine adherence to treatment. Patients in the adherent group—65% of the population—were found to have significantly lower depression scores compared with the nonadherent group. Memory scores were not robustly correlated with adherence. The authors conclude that physicians should consider targeting patients with epilepsy and comorbid depression as they may be at a higher risk of nonadherence.
McAuley JW, Passen N, Prusa C, Dixon J, Cotterman-Hart S, Shneker BF. An evaluation of the impact of memory and mood on antiepileptic drug adherence. Epilepsy Behav. 2015;43:61-65.
In a cross-sectional study, one hundred patients with epilepsy on antiepileptic drug (AED) therapy were observed to determine adherence to treatment. Patients in the adherent group—65% of the population—were found to have significantly lower depression scores compared with the nonadherent group. Memory scores were not robustly correlated with adherence. The authors conclude that physicians should consider targeting patients with epilepsy and comorbid depression as they may be at a higher risk of nonadherence.
McAuley JW, Passen N, Prusa C, Dixon J, Cotterman-Hart S, Shneker BF. An evaluation of the impact of memory and mood on antiepileptic drug adherence. Epilepsy Behav. 2015;43:61-65.
Why Do Patients With Epilepsy Delay Considering Surgical Treatment?
Fear of surgery, ignorance of treatment options, and tolerance of symptoms are the primary responses found to influence treatment-decision making for patients with epilepsy who are eligible for surgical treatment. Researchers examined twelve papers that examined patient perceptions of epilepsy surgery and physician attitudes. The authors conclude that patient and physician treatment misperceptions can lead to undertreatment and serious health consequences.
Dewar SR, Pieters HC. Perceptions of epilepsy surgery: a systematic review and an explanatory model of decision-making. Epilepsy Behav. 2015;44C:171-178.
Fear of surgery, ignorance of treatment options, and tolerance of symptoms are the primary responses found to influence treatment-decision making for patients with epilepsy who are eligible for surgical treatment. Researchers examined twelve papers that examined patient perceptions of epilepsy surgery and physician attitudes. The authors conclude that patient and physician treatment misperceptions can lead to undertreatment and serious health consequences.
Dewar SR, Pieters HC. Perceptions of epilepsy surgery: a systematic review and an explanatory model of decision-making. Epilepsy Behav. 2015;44C:171-178.
Fear of surgery, ignorance of treatment options, and tolerance of symptoms are the primary responses found to influence treatment-decision making for patients with epilepsy who are eligible for surgical treatment. Researchers examined twelve papers that examined patient perceptions of epilepsy surgery and physician attitudes. The authors conclude that patient and physician treatment misperceptions can lead to undertreatment and serious health consequences.
Dewar SR, Pieters HC. Perceptions of epilepsy surgery: a systematic review and an explanatory model of decision-making. Epilepsy Behav. 2015;44C:171-178.
Can Nomograms Be Used to Predict Seizure Outcomes Postsurgery?
Researchers at the Cleveland Clinic Epilepsy Center developed nomograms to predict freedom from seizures and Engel score of 1 (eventual freedom from seizures) based on a development cohort of 846 patients who had resective surgery between 1996 and 2011. The nomograms were tested in an external validation cohort of 604 patients from 4 epilepsy surgery centers. If these nomograms are validated they could be used to predict seizure outcomes in patients eligible for epilepsy surgery.
Jehi L, Yardi R, Chagin K, et al. Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis. Lancet Neurol. 2015;14(3):283-290.
Researchers at the Cleveland Clinic Epilepsy Center developed nomograms to predict freedom from seizures and Engel score of 1 (eventual freedom from seizures) based on a development cohort of 846 patients who had resective surgery between 1996 and 2011. The nomograms were tested in an external validation cohort of 604 patients from 4 epilepsy surgery centers. If these nomograms are validated they could be used to predict seizure outcomes in patients eligible for epilepsy surgery.
Jehi L, Yardi R, Chagin K, et al. Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis. Lancet Neurol. 2015;14(3):283-290.
Researchers at the Cleveland Clinic Epilepsy Center developed nomograms to predict freedom from seizures and Engel score of 1 (eventual freedom from seizures) based on a development cohort of 846 patients who had resective surgery between 1996 and 2011. The nomograms were tested in an external validation cohort of 604 patients from 4 epilepsy surgery centers. If these nomograms are validated they could be used to predict seizure outcomes in patients eligible for epilepsy surgery.
Jehi L, Yardi R, Chagin K, et al. Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis. Lancet Neurol. 2015;14(3):283-290.
Improving General Health in People with Epilepsy
Researchers found that people with epilepsy are less likely to get the recommended amount of sleep or levels of physical activity compared with patients without epilepsy. The study examined data from the 2010 cross-sectional National Health Interview Survey and found that 22% of adults with active epilepsy smoked and only 35% with active epilepsy met the recommended physical activity guidelines. In addition, only half of patients with active epilepsy slept the recommended 7 or 8 hours each day.
Cui W, Zack MM, Kobau R, Helmers SL. Health behaviors among people with epilepsy—results from the 2010 National Health Interview Survey. Epilepsy Behav. 2015;44C:121-126.
Researchers found that people with epilepsy are less likely to get the recommended amount of sleep or levels of physical activity compared with patients without epilepsy. The study examined data from the 2010 cross-sectional National Health Interview Survey and found that 22% of adults with active epilepsy smoked and only 35% with active epilepsy met the recommended physical activity guidelines. In addition, only half of patients with active epilepsy slept the recommended 7 or 8 hours each day.
Cui W, Zack MM, Kobau R, Helmers SL. Health behaviors among people with epilepsy—results from the 2010 National Health Interview Survey. Epilepsy Behav. 2015;44C:121-126.
Researchers found that people with epilepsy are less likely to get the recommended amount of sleep or levels of physical activity compared with patients without epilepsy. The study examined data from the 2010 cross-sectional National Health Interview Survey and found that 22% of adults with active epilepsy smoked and only 35% with active epilepsy met the recommended physical activity guidelines. In addition, only half of patients with active epilepsy slept the recommended 7 or 8 hours each day.
Cui W, Zack MM, Kobau R, Helmers SL. Health behaviors among people with epilepsy—results from the 2010 National Health Interview Survey. Epilepsy Behav. 2015;44C:121-126.
Is Body Position Associated with SUDEP?
In this meta-analysis, researchers analyzed body positions of 253 cases of sudden unexpected death in epilepsy (SUDEP), revealing that 73.3% of patients died in the prone position while 26.7% died in nonprone positions. In addition, all 11 cases of video-EEG-monitored SUDEP reported the prone position. In a subgroup of 88 SUDEP cases, the prone position was reported in 85.7% of cases of patients aged ≤40 years and 60% in patients >40 years. The authors suggest that prone position is a major risk factor for SUDEP, especially in patients aged ≤40 years.
Liebenthal JA, Wu S, Rose S, Ebersole JS, Tao JX. Association of prone position with sudden unexpected death in epilepsy. Neurology. 2015;84(7):703-709.
In this meta-analysis, researchers analyzed body positions of 253 cases of sudden unexpected death in epilepsy (SUDEP), revealing that 73.3% of patients died in the prone position while 26.7% died in nonprone positions. In addition, all 11 cases of video-EEG-monitored SUDEP reported the prone position. In a subgroup of 88 SUDEP cases, the prone position was reported in 85.7% of cases of patients aged ≤40 years and 60% in patients >40 years. The authors suggest that prone position is a major risk factor for SUDEP, especially in patients aged ≤40 years.
Liebenthal JA, Wu S, Rose S, Ebersole JS, Tao JX. Association of prone position with sudden unexpected death in epilepsy. Neurology. 2015;84(7):703-709.
In this meta-analysis, researchers analyzed body positions of 253 cases of sudden unexpected death in epilepsy (SUDEP), revealing that 73.3% of patients died in the prone position while 26.7% died in nonprone positions. In addition, all 11 cases of video-EEG-monitored SUDEP reported the prone position. In a subgroup of 88 SUDEP cases, the prone position was reported in 85.7% of cases of patients aged ≤40 years and 60% in patients >40 years. The authors suggest that prone position is a major risk factor for SUDEP, especially in patients aged ≤40 years.
Liebenthal JA, Wu S, Rose S, Ebersole JS, Tao JX. Association of prone position with sudden unexpected death in epilepsy. Neurology. 2015;84(7):703-709.
Can a Seizure Freedom Score Predict Success in Epilepsy Surgery?
Postoperative seizure freedom could be predicted using an easily measurable seizure freedom score (SFS) according to researchers from the Cleveland Clinic Epilepsy Center. The SFS was calculated by compiling 4 predictive outcome indicators: preoperative seizure frequency, history of generalized tonic-clonic seizures, brain MRI, and epilepsy duration. In a study population of 466 patients, seizure freedom rates were directly correlated with SFS scores. The authors propose that this tool may be beneficial for estimation of surgical candidacy and will help with patient and family counseling.
Garcia Gracia C, Yardi R, Kattan MW, et al. Seizure freedom score: a new simple method to predict success of epilepsy surgery. Epilepsia. 2015;56(3):359-365.
Postoperative seizure freedom could be predicted using an easily measurable seizure freedom score (SFS) according to researchers from the Cleveland Clinic Epilepsy Center. The SFS was calculated by compiling 4 predictive outcome indicators: preoperative seizure frequency, history of generalized tonic-clonic seizures, brain MRI, and epilepsy duration. In a study population of 466 patients, seizure freedom rates were directly correlated with SFS scores. The authors propose that this tool may be beneficial for estimation of surgical candidacy and will help with patient and family counseling.
Garcia Gracia C, Yardi R, Kattan MW, et al. Seizure freedom score: a new simple method to predict success of epilepsy surgery. Epilepsia. 2015;56(3):359-365.
Postoperative seizure freedom could be predicted using an easily measurable seizure freedom score (SFS) according to researchers from the Cleveland Clinic Epilepsy Center. The SFS was calculated by compiling 4 predictive outcome indicators: preoperative seizure frequency, history of generalized tonic-clonic seizures, brain MRI, and epilepsy duration. In a study population of 466 patients, seizure freedom rates were directly correlated with SFS scores. The authors propose that this tool may be beneficial for estimation of surgical candidacy and will help with patient and family counseling.
Garcia Gracia C, Yardi R, Kattan MW, et al. Seizure freedom score: a new simple method to predict success of epilepsy surgery. Epilepsia. 2015;56(3):359-365.