Q2. Correct Answer: A  
 
Rationale:  
In a patient with chronic pancreatitis and a pancreatic mass, the most likely etiology is adenocarcinoma. This patient has radiologically resectable pancreas cancer. There is no evidence of lymphadenopathy or vascular invasion. Performing an ERCP with stent placement to relieve biliary obstruction has not been shown to be of benefit in patients with a resectable pancreatic mass. In fact, surgical outcomes are worse if a stent is placed in the bile duct. Surgical consultation should be obtained and the patient should undergo pancreaticoduodenectomy. EUS is sometimes done, but most cases of resectable disease should go straight to surgery.  
 
Reference  
Ghaneh P, et al. Biology and management of pancreatic cancer. Gut 2007;56(8)1134-52. 
 
ginews@gastro.org

Q2. Correct Answer: A  
 
Rationale:  
In a patient with chronic pancreatitis and a pancreatic mass, the most likely etiology is adenocarcinoma. This patient has radiologically resectable pancreas cancer. There is no evidence of lymphadenopathy or vascular invasion. Performing an ERCP with stent placement to relieve biliary obstruction has not been shown to be of benefit in patients with a resectable pancreatic mass. In fact, surgical outcomes are worse if a stent is placed in the bile duct. Surgical consultation should be obtained and the patient should undergo pancreaticoduodenectomy. EUS is sometimes done, but most cases of resectable disease should go straight to surgery.  
 
Reference  
Ghaneh P, et al. Biology and management of pancreatic cancer. Gut 2007;56(8)1134-52. 
 
ginews@gastro.org

Q2. Correct Answer: A  
 
Rationale:  
In a patient with chronic pancreatitis and a pancreatic mass, the most likely etiology is adenocarcinoma. This patient has radiologically resectable pancreas cancer. There is no evidence of lymphadenopathy or vascular invasion. Performing an ERCP with stent placement to relieve biliary obstruction has not been shown to be of benefit in patients with a resectable pancreatic mass. In fact, surgical outcomes are worse if a stent is placed in the bile duct. Surgical consultation should be obtained and the patient should undergo pancreaticoduodenectomy. EUS is sometimes done, but most cases of resectable disease should go straight to surgery.  
 
Reference  
Ghaneh P, et al. Biology and management of pancreatic cancer. Gut 2007;56(8)1134-52. 
 
ginews@gastro.org

Q1. Correct Answer: B  
 
Rationale:  
Risk factors for gallstone formation include increased age, female gender, pregnancy, dyslipidemia, diabetes, obesity and rapid weight loss - especially after gastric bypass surgery. Medications such as hormone replacement therapies/ oral contraceptive agents, fibrates, somatostatin analogues also increase gallstone risk. Currently, there is evidence suggesting potential benefit of prophylactic cholecystectomy during Roux-en-Y gastric bypass, given the potential risk of gallstone formation with rapid weight loss following surgery. However, there is also data from randomized controlled trials that the use of ursodeoxycholic acid following surgery may help reduce risk of gallstone formation for this group of patients.  
 
Reference: 
Stokes et al. Ursodeoxycholic acid and diets higher in fat prevent gallbladder Stones during weight loss: A meta-analysis of randomized controlled trials. 2014. Clin Gastroenterol Hepatol. 2014;12:1090-100. 

Q1. Correct Answer: B  
 
Rationale:  
Risk factors for gallstone formation include increased age, female gender, pregnancy, dyslipidemia, diabetes, obesity and rapid weight loss - especially after gastric bypass surgery. Medications such as hormone replacement therapies/ oral contraceptive agents, fibrates, somatostatin analogues also increase gallstone risk. Currently, there is evidence suggesting potential benefit of prophylactic cholecystectomy during Roux-en-Y gastric bypass, given the potential risk of gallstone formation with rapid weight loss following surgery. However, there is also data from randomized controlled trials that the use of ursodeoxycholic acid following surgery may help reduce risk of gallstone formation for this group of patients.  
 
Reference: 
Stokes et al. Ursodeoxycholic acid and diets higher in fat prevent gallbladder Stones during weight loss: A meta-analysis of randomized controlled trials. 2014. Clin Gastroenterol Hepatol. 2014;12:1090-100. 

Q1. Correct Answer: B  
 
Rationale:  
Risk factors for gallstone formation include increased age, female gender, pregnancy, dyslipidemia, diabetes, obesity and rapid weight loss - especially after gastric bypass surgery. Medications such as hormone replacement therapies/ oral contraceptive agents, fibrates, somatostatin analogues also increase gallstone risk. Currently, there is evidence suggesting potential benefit of prophylactic cholecystectomy during Roux-en-Y gastric bypass, given the potential risk of gallstone formation with rapid weight loss following surgery. However, there is also data from randomized controlled trials that the use of ursodeoxycholic acid following surgery may help reduce risk of gallstone formation for this group of patients.  
 
Reference: 
Stokes et al. Ursodeoxycholic acid and diets higher in fat prevent gallbladder Stones during weight loss: A meta-analysis of randomized controlled trials. 2014. Clin Gastroenterol Hepatol. 2014;12:1090-100. 

Adding local treatment to systemic therapy may extend survival among certain patients with oligometastatic non–small cell lung cancer (NSCLC), according to a retrospective look at more than 34,000 patients.

Surgical resection provided the greatest survival benefit, followed by external beam radiotherapy or thermal ablation (EBRT/TA), reported lead author Johannes Uhlig, MD, of University Medical Center Göttingen (Germany) and colleagues.

NSCLC patients with five or fewer metastatic sites (oligometastatic disease) are thought to achieve better outcomes than patients with more widely disseminated disease, the investigators noted in JAMA Network Open, but the benefit of local therapy for this population is unclear.

“A recent randomized, prospective study of 74 patients with oligometastatic NSCLC identified superior progression-free survival with local control after hypofractionated radiotherapy or surgical resection and radiotherapy compared with systemic therapy alone, suggesting an important application of local treatment options for patients with metastatic disease,” the investigators wrote.

To build on these findings, the investigators retrospectively evaluated 34,887 patients with stage IV NSCLC who had up to one distant metastatic lesion in the liver, lung, brain, or bone, as documented in the National Cancer Database. Treatment groups were divided into patients who received systemic therapy alone, surgical resection plus systemic therapy, or EBRT/TA plus systemic therapy. Multivariable Cox proportional hazards models were used to compare overall survival among the three groups.

Including a median follow-up of 39.4 months, data analysis showed that patients who underwent surgery and systemic therapy fared the best. Adding surgery reduced mortality risk by 38% and 41%, compared with EBRT/TA plus systemic therapy and systemic therapy alone, respectively (P less than .001 for both). Compared with systemic therapy alone, adding EBRT/TA reduced mortality risk by 5% (P = .002).

The impact of EBRT/TA varied among subgroups. For those with squamous cell carcinoma who had limited nodal disease, adding EBRT/TA resulted in a clear benefit, reducing mortality risk by 32% (P less than .001). Compared with systemic therapy alone, this benefit translated to higher survival rates for up to 3 years. Conversely, adding EBRT/TA increased risk of death by 39% among patients with extended local and distant adenocarcinoma (P less than .001). In this subgroup, survival rates over the next 3 years were higher among patients treated with systemic therapy alone.

“The present study supports a combined approach of local therapy in addition to systemic treatment for select patients with oligometastatic NSCLC,” the investigators concluded.

The study was funded by the U.S. Department of Defense. The investigators disclosed additional relationships with Bayer, AstraZeneca, Bristol-Myers Squibb, and others.

SOURCE: Uhlig et al. JAMA Netw Open. 2019 Aug 21. doi: 10.1001/jamanetworkopen.2019.9702.

Adding local treatment to systemic therapy may extend survival among certain patients with oligometastatic non–small cell lung cancer (NSCLC), according to a retrospective look at more than 34,000 patients.

Surgical resection provided the greatest survival benefit, followed by external beam radiotherapy or thermal ablation (EBRT/TA), reported lead author Johannes Uhlig, MD, of University Medical Center Göttingen (Germany) and colleagues.

NSCLC patients with five or fewer metastatic sites (oligometastatic disease) are thought to achieve better outcomes than patients with more widely disseminated disease, the investigators noted in JAMA Network Open, but the benefit of local therapy for this population is unclear.

“A recent randomized, prospective study of 74 patients with oligometastatic NSCLC identified superior progression-free survival with local control after hypofractionated radiotherapy or surgical resection and radiotherapy compared with systemic therapy alone, suggesting an important application of local treatment options for patients with metastatic disease,” the investigators wrote.

To build on these findings, the investigators retrospectively evaluated 34,887 patients with stage IV NSCLC who had up to one distant metastatic lesion in the liver, lung, brain, or bone, as documented in the National Cancer Database. Treatment groups were divided into patients who received systemic therapy alone, surgical resection plus systemic therapy, or EBRT/TA plus systemic therapy. Multivariable Cox proportional hazards models were used to compare overall survival among the three groups.

Including a median follow-up of 39.4 months, data analysis showed that patients who underwent surgery and systemic therapy fared the best. Adding surgery reduced mortality risk by 38% and 41%, compared with EBRT/TA plus systemic therapy and systemic therapy alone, respectively (P less than .001 for both). Compared with systemic therapy alone, adding EBRT/TA reduced mortality risk by 5% (P = .002).

The impact of EBRT/TA varied among subgroups. For those with squamous cell carcinoma who had limited nodal disease, adding EBRT/TA resulted in a clear benefit, reducing mortality risk by 32% (P less than .001). Compared with systemic therapy alone, this benefit translated to higher survival rates for up to 3 years. Conversely, adding EBRT/TA increased risk of death by 39% among patients with extended local and distant adenocarcinoma (P less than .001). In this subgroup, survival rates over the next 3 years were higher among patients treated with systemic therapy alone.

“The present study supports a combined approach of local therapy in addition to systemic treatment for select patients with oligometastatic NSCLC,” the investigators concluded.

The study was funded by the U.S. Department of Defense. The investigators disclosed additional relationships with Bayer, AstraZeneca, Bristol-Myers Squibb, and others.

SOURCE: Uhlig et al. JAMA Netw Open. 2019 Aug 21. doi: 10.1001/jamanetworkopen.2019.9702.

Adding local treatment to systemic therapy may extend survival among certain patients with oligometastatic non–small cell lung cancer (NSCLC), according to a retrospective look at more than 34,000 patients.

Surgical resection provided the greatest survival benefit, followed by external beam radiotherapy or thermal ablation (EBRT/TA), reported lead author Johannes Uhlig, MD, of University Medical Center Göttingen (Germany) and colleagues.

NSCLC patients with five or fewer metastatic sites (oligometastatic disease) are thought to achieve better outcomes than patients with more widely disseminated disease, the investigators noted in JAMA Network Open, but the benefit of local therapy for this population is unclear.

“A recent randomized, prospective study of 74 patients with oligometastatic NSCLC identified superior progression-free survival with local control after hypofractionated radiotherapy or surgical resection and radiotherapy compared with systemic therapy alone, suggesting an important application of local treatment options for patients with metastatic disease,” the investigators wrote.

To build on these findings, the investigators retrospectively evaluated 34,887 patients with stage IV NSCLC who had up to one distant metastatic lesion in the liver, lung, brain, or bone, as documented in the National Cancer Database. Treatment groups were divided into patients who received systemic therapy alone, surgical resection plus systemic therapy, or EBRT/TA plus systemic therapy. Multivariable Cox proportional hazards models were used to compare overall survival among the three groups.

Including a median follow-up of 39.4 months, data analysis showed that patients who underwent surgery and systemic therapy fared the best. Adding surgery reduced mortality risk by 38% and 41%, compared with EBRT/TA plus systemic therapy and systemic therapy alone, respectively (P less than .001 for both). Compared with systemic therapy alone, adding EBRT/TA reduced mortality risk by 5% (P = .002).

The impact of EBRT/TA varied among subgroups. For those with squamous cell carcinoma who had limited nodal disease, adding EBRT/TA resulted in a clear benefit, reducing mortality risk by 32% (P less than .001). Compared with systemic therapy alone, this benefit translated to higher survival rates for up to 3 years. Conversely, adding EBRT/TA increased risk of death by 39% among patients with extended local and distant adenocarcinoma (P less than .001). In this subgroup, survival rates over the next 3 years were higher among patients treated with systemic therapy alone.

“The present study supports a combined approach of local therapy in addition to systemic treatment for select patients with oligometastatic NSCLC,” the investigators concluded.

The study was funded by the U.S. Department of Defense. The investigators disclosed additional relationships with Bayer, AstraZeneca, Bristol-Myers Squibb, and others.

SOURCE: Uhlig et al. JAMA Netw Open. 2019 Aug 21. doi: 10.1001/jamanetworkopen.2019.9702.

The staff of MDedge Rheumatology/Rheumatology News are happy to announce that Melissa S. Oliver, MD, and C. Kent Kwoh, MD, have joined the editorial advisory board.

Dr. Oliver is an assistant professor of clinical pediatrics in the department of pediatric rheumatology at Indiana University and practices at Riley Hospital for Children, both in Indianapolis. She completed her training in pediatrics at New Jersey Medical School, Newark, and Pediatric Rheumatology at Stanford (Calif.) University.

Her research interests include improving patient outcomes in the juvenile spondyloarthropathy and chronic nonbacterial osteomyelitis populations. She is an active member of the Childhood Arthritis & Rheumatology Research Alliance.

Dr. Kwoh is director of the University of Arizona Arthritis Center, Tucson. He holds the Charles A.L. and Suzanne M. Stephens Endowed Chair in Rheumatology and is the chief of the division of rheumatology and professor of medicine and medical imaging at the university.

His current major research interests focus on the identification of biomarkers – most notably MRI imaging biomarkers for the development and/or progression of knee OA and the characterization of knee pain patterns in OA. He also has a major interest in the reduction and ultimately the elimination of disparities in the management of arthritis and musculoskeletal diseases.

jevans@mdedge.com

The staff of MDedge Rheumatology/Rheumatology News are happy to announce that Melissa S. Oliver, MD, and C. Kent Kwoh, MD, have joined the editorial advisory board.

Dr. Oliver is an assistant professor of clinical pediatrics in the department of pediatric rheumatology at Indiana University and practices at Riley Hospital for Children, both in Indianapolis. She completed her training in pediatrics at New Jersey Medical School, Newark, and Pediatric Rheumatology at Stanford (Calif.) University.

Her research interests include improving patient outcomes in the juvenile spondyloarthropathy and chronic nonbacterial osteomyelitis populations. She is an active member of the Childhood Arthritis & Rheumatology Research Alliance.

Dr. Kwoh is director of the University of Arizona Arthritis Center, Tucson. He holds the Charles A.L. and Suzanne M. Stephens Endowed Chair in Rheumatology and is the chief of the division of rheumatology and professor of medicine and medical imaging at the university.

His current major research interests focus on the identification of biomarkers – most notably MRI imaging biomarkers for the development and/or progression of knee OA and the characterization of knee pain patterns in OA. He also has a major interest in the reduction and ultimately the elimination of disparities in the management of arthritis and musculoskeletal diseases.

jevans@mdedge.com

The staff of MDedge Rheumatology/Rheumatology News are happy to announce that Melissa S. Oliver, MD, and C. Kent Kwoh, MD, have joined the editorial advisory board.

Dr. Oliver is an assistant professor of clinical pediatrics in the department of pediatric rheumatology at Indiana University and practices at Riley Hospital for Children, both in Indianapolis. She completed her training in pediatrics at New Jersey Medical School, Newark, and Pediatric Rheumatology at Stanford (Calif.) University.

Her research interests include improving patient outcomes in the juvenile spondyloarthropathy and chronic nonbacterial osteomyelitis populations. She is an active member of the Childhood Arthritis & Rheumatology Research Alliance.

Dr. Kwoh is director of the University of Arizona Arthritis Center, Tucson. He holds the Charles A.L. and Suzanne M. Stephens Endowed Chair in Rheumatology and is the chief of the division of rheumatology and professor of medicine and medical imaging at the university.

His current major research interests focus on the identification of biomarkers – most notably MRI imaging biomarkers for the development and/or progression of knee OA and the characterization of knee pain patterns in OA. He also has a major interest in the reduction and ultimately the elimination of disparities in the management of arthritis and musculoskeletal diseases.

jevans@mdedge.com

Showing cancer patients receiving chemotherapy short videos about their treatments has the potential to improve their understanding about the treatments they are receiving, new research in Cancer has shown.

Researchers showed 50 patients at an underserved hospital six 1-minute videos focused on important terms related to their chemotherapy treatments and found that the videos helped them better understand what those key terms mean. Before viewing the videos, 15 of 20 terms were misunderstood by more than one third of patients, with 98% unable to define “maintenance,” 74% unable to define “cancer,” and 58% unable to define “chemotherapy.” Six pilot educational videos describing a narrowed down list of six terms were created, and patient understanding of all six terms improved by at least 20% after watching the videos. The six terms defined in the videos were “palliative chemotherapy,” “curative,” “cancer,” “blood count,” “risk of infection,” and “chemotherapy.”

“Although a current concern is that precision medicines will not be understood due to genetic illiteracy and misunderstandings about the immune system, it is important to remember that the terminology used to describe chemotherapy, the backbone of many cancer treatments, may also be incomprehensible to some patients,” Rebecca Pentz, PhD, of Emory University, Atlanta, and colleagues wrote.

“Our video pilot suggests that multimedia can help patients understand chemotherapy terminology,” Dr. Pentz and colleagues said. “For each term, there was at least a 20% increase in patient understanding after watching the video. None of the patients could define palliative chemotherapy before watching the video, but 72% were able to provide a definition afterward.”

Researchers noted that the term most understood after the video was curative treatment (patients being able to define the phrase grew from 34% to 88%).

“Our study establishes that basic chemotherapy terminology is widely misunderstood by an underserved population, but that video-based education can significantly increase patient understanding,” the investigators concluded, but noted the research was limited by the small number of videos as well as the single underserved hospital, which may limit the generalizablility of the study.

Dr. Pentz and colleagues added that “education of physicians about the severe patient lack of understanding of basic cancer terminology and methods to improve understanding would be most helpful.”

SOURCE: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.

Showing cancer patients receiving chemotherapy short videos about their treatments has the potential to improve their understanding about the treatments they are receiving, new research in Cancer has shown.

Researchers showed 50 patients at an underserved hospital six 1-minute videos focused on important terms related to their chemotherapy treatments and found that the videos helped them better understand what those key terms mean. Before viewing the videos, 15 of 20 terms were misunderstood by more than one third of patients, with 98% unable to define “maintenance,” 74% unable to define “cancer,” and 58% unable to define “chemotherapy.” Six pilot educational videos describing a narrowed down list of six terms were created, and patient understanding of all six terms improved by at least 20% after watching the videos. The six terms defined in the videos were “palliative chemotherapy,” “curative,” “cancer,” “blood count,” “risk of infection,” and “chemotherapy.”

“Although a current concern is that precision medicines will not be understood due to genetic illiteracy and misunderstandings about the immune system, it is important to remember that the terminology used to describe chemotherapy, the backbone of many cancer treatments, may also be incomprehensible to some patients,” Rebecca Pentz, PhD, of Emory University, Atlanta, and colleagues wrote.

“Our video pilot suggests that multimedia can help patients understand chemotherapy terminology,” Dr. Pentz and colleagues said. “For each term, there was at least a 20% increase in patient understanding after watching the video. None of the patients could define palliative chemotherapy before watching the video, but 72% were able to provide a definition afterward.”

Researchers noted that the term most understood after the video was curative treatment (patients being able to define the phrase grew from 34% to 88%).

“Our study establishes that basic chemotherapy terminology is widely misunderstood by an underserved population, but that video-based education can significantly increase patient understanding,” the investigators concluded, but noted the research was limited by the small number of videos as well as the single underserved hospital, which may limit the generalizablility of the study.

Dr. Pentz and colleagues added that “education of physicians about the severe patient lack of understanding of basic cancer terminology and methods to improve understanding would be most helpful.”

SOURCE: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.

Showing cancer patients receiving chemotherapy short videos about their treatments has the potential to improve their understanding about the treatments they are receiving, new research in Cancer has shown.

Researchers showed 50 patients at an underserved hospital six 1-minute videos focused on important terms related to their chemotherapy treatments and found that the videos helped them better understand what those key terms mean. Before viewing the videos, 15 of 20 terms were misunderstood by more than one third of patients, with 98% unable to define “maintenance,” 74% unable to define “cancer,” and 58% unable to define “chemotherapy.” Six pilot educational videos describing a narrowed down list of six terms were created, and patient understanding of all six terms improved by at least 20% after watching the videos. The six terms defined in the videos were “palliative chemotherapy,” “curative,” “cancer,” “blood count,” “risk of infection,” and “chemotherapy.”

“Although a current concern is that precision medicines will not be understood due to genetic illiteracy and misunderstandings about the immune system, it is important to remember that the terminology used to describe chemotherapy, the backbone of many cancer treatments, may also be incomprehensible to some patients,” Rebecca Pentz, PhD, of Emory University, Atlanta, and colleagues wrote.

“Our video pilot suggests that multimedia can help patients understand chemotherapy terminology,” Dr. Pentz and colleagues said. “For each term, there was at least a 20% increase in patient understanding after watching the video. None of the patients could define palliative chemotherapy before watching the video, but 72% were able to provide a definition afterward.”

Researchers noted that the term most understood after the video was curative treatment (patients being able to define the phrase grew from 34% to 88%).

“Our study establishes that basic chemotherapy terminology is widely misunderstood by an underserved population, but that video-based education can significantly increase patient understanding,” the investigators concluded, but noted the research was limited by the small number of videos as well as the single underserved hospital, which may limit the generalizablility of the study.

Dr. Pentz and colleagues added that “education of physicians about the severe patient lack of understanding of basic cancer terminology and methods to improve understanding would be most helpful.”

SOURCE: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.

BANGKOK – Intranasal midazolam is a legitimate first-line option for treatment of status epilepticus in patients who don’t already have an intravenous line in place, Lara Kay, MD, said at the International Epilepsy Congress.

Bruce Jancin/MDedge News

Why? Because status epilepticus is a major medical emergency. It’s associated with substantial morbidity and mortality. And of the various factors that influence outcome in status epilepticus – including age, underlying etiology, and level of consciousness – only one is potentially within physician control: time to treatment, she noted at the congress sponsored by the International League Against Epilepsy.

“Time is brain,” observed Dr. Kay, a neurologist at the epilepsy center at University Hospital Frankfurt.

While intravenous benzodiazepines – for example, lorazepam at 2-4 mg – are widely accepted as the time-honored first-line treatment for status epilepticus, trying to place a line in a patient experiencing this emergency can be a tricky, time-consuming business. Multiple studies have demonstrated that various nonintravenous formulations of benzodiazepines, such as rectal diazepam or buccal or intramuscular midazolam, can be administered much faster and are as effective as intravenous benzodiazepines. But buccal midazolam is quite expensive in Germany, and the ready-to-use intramuscular midazolam applicator that’s available in the United States isn’t marketed in Germany. So several years ago Dr. Kay and her fellow neurologists started having their university hospital pharmacy manufacture intranasal midazolam.

Dr. Kay presented an observational study of 42 consecutive patients with status epilepticus who received intranasal midazolam as first-line treatment. The patients had a mean age of nearly 53 years and 23 were women. The starting dose was 2.5 mg per nostril, moving up to 5 mg per nostril after waiting 5 minutes in initial nonresponders.

Status epilepticus ceased both clinically and by EEG in 24 of the 42 patients, or 57%, in an average of 5 minutes after administration of the intranasal medication at a mean dose of 5.6 mg. Nonresponders received a mean dose of 7.5 mg. There were no significant differences between responders and nonresponders in terms of the proportion presenting with preexisting epilepsy or the epilepsy etiology. However, responders presented at a mean of 54 minutes in status epilepticus, while nonresponders had been in status for 17 minutes.

The 57% response rate with intranasal midazolam is comparable with other investigators’ reported success rates using other benzodiazepines and routes of administration, she noted.

Session cochair Gregory Krauss, MD, commented that he thought the Frankfurt neurologists may have been too cautious in their dosing of intranasal midazolam for status epilepticus.

“Often in the U.S. 5 mg is initially used in each nostril,” according to Dr. Krauss, professor of neurology at Johns Hopkins University, Baltimore.

Dr. Kay reported having no financial conflicts of interest regarding her study.

bjancin@mdedge.com

SOURCE: Kay L et al. IEC 2019, Abstract P029.

BANGKOK – Intranasal midazolam is a legitimate first-line option for treatment of status epilepticus in patients who don’t already have an intravenous line in place, Lara Kay, MD, said at the International Epilepsy Congress.

Bruce Jancin/MDedge News

Why? Because status epilepticus is a major medical emergency. It’s associated with substantial morbidity and mortality. And of the various factors that influence outcome in status epilepticus – including age, underlying etiology, and level of consciousness – only one is potentially within physician control: time to treatment, she noted at the congress sponsored by the International League Against Epilepsy.

“Time is brain,” observed Dr. Kay, a neurologist at the epilepsy center at University Hospital Frankfurt.

While intravenous benzodiazepines – for example, lorazepam at 2-4 mg – are widely accepted as the time-honored first-line treatment for status epilepticus, trying to place a line in a patient experiencing this emergency can be a tricky, time-consuming business. Multiple studies have demonstrated that various nonintravenous formulations of benzodiazepines, such as rectal diazepam or buccal or intramuscular midazolam, can be administered much faster and are as effective as intravenous benzodiazepines. But buccal midazolam is quite expensive in Germany, and the ready-to-use intramuscular midazolam applicator that’s available in the United States isn’t marketed in Germany. So several years ago Dr. Kay and her fellow neurologists started having their university hospital pharmacy manufacture intranasal midazolam.

Dr. Kay presented an observational study of 42 consecutive patients with status epilepticus who received intranasal midazolam as first-line treatment. The patients had a mean age of nearly 53 years and 23 were women. The starting dose was 2.5 mg per nostril, moving up to 5 mg per nostril after waiting 5 minutes in initial nonresponders.

Status epilepticus ceased both clinically and by EEG in 24 of the 42 patients, or 57%, in an average of 5 minutes after administration of the intranasal medication at a mean dose of 5.6 mg. Nonresponders received a mean dose of 7.5 mg. There were no significant differences between responders and nonresponders in terms of the proportion presenting with preexisting epilepsy or the epilepsy etiology. However, responders presented at a mean of 54 minutes in status epilepticus, while nonresponders had been in status for 17 minutes.

The 57% response rate with intranasal midazolam is comparable with other investigators’ reported success rates using other benzodiazepines and routes of administration, she noted.

Session cochair Gregory Krauss, MD, commented that he thought the Frankfurt neurologists may have been too cautious in their dosing of intranasal midazolam for status epilepticus.

“Often in the U.S. 5 mg is initially used in each nostril,” according to Dr. Krauss, professor of neurology at Johns Hopkins University, Baltimore.

Dr. Kay reported having no financial conflicts of interest regarding her study.

bjancin@mdedge.com

SOURCE: Kay L et al. IEC 2019, Abstract P029.

BANGKOK – Intranasal midazolam is a legitimate first-line option for treatment of status epilepticus in patients who don’t already have an intravenous line in place, Lara Kay, MD, said at the International Epilepsy Congress.

Bruce Jancin/MDedge News

Why? Because status epilepticus is a major medical emergency. It’s associated with substantial morbidity and mortality. And of the various factors that influence outcome in status epilepticus – including age, underlying etiology, and level of consciousness – only one is potentially within physician control: time to treatment, she noted at the congress sponsored by the International League Against Epilepsy.

“Time is brain,” observed Dr. Kay, a neurologist at the epilepsy center at University Hospital Frankfurt.

While intravenous benzodiazepines – for example, lorazepam at 2-4 mg – are widely accepted as the time-honored first-line treatment for status epilepticus, trying to place a line in a patient experiencing this emergency can be a tricky, time-consuming business. Multiple studies have demonstrated that various nonintravenous formulations of benzodiazepines, such as rectal diazepam or buccal or intramuscular midazolam, can be administered much faster and are as effective as intravenous benzodiazepines. But buccal midazolam is quite expensive in Germany, and the ready-to-use intramuscular midazolam applicator that’s available in the United States isn’t marketed in Germany. So several years ago Dr. Kay and her fellow neurologists started having their university hospital pharmacy manufacture intranasal midazolam.

Dr. Kay presented an observational study of 42 consecutive patients with status epilepticus who received intranasal midazolam as first-line treatment. The patients had a mean age of nearly 53 years and 23 were women. The starting dose was 2.5 mg per nostril, moving up to 5 mg per nostril after waiting 5 minutes in initial nonresponders.

Status epilepticus ceased both clinically and by EEG in 24 of the 42 patients, or 57%, in an average of 5 minutes after administration of the intranasal medication at a mean dose of 5.6 mg. Nonresponders received a mean dose of 7.5 mg. There were no significant differences between responders and nonresponders in terms of the proportion presenting with preexisting epilepsy or the epilepsy etiology. However, responders presented at a mean of 54 minutes in status epilepticus, while nonresponders had been in status for 17 minutes.

The 57% response rate with intranasal midazolam is comparable with other investigators’ reported success rates using other benzodiazepines and routes of administration, she noted.

Session cochair Gregory Krauss, MD, commented that he thought the Frankfurt neurologists may have been too cautious in their dosing of intranasal midazolam for status epilepticus.

“Often in the U.S. 5 mg is initially used in each nostril,” according to Dr. Krauss, professor of neurology at Johns Hopkins University, Baltimore.

Dr. Kay reported having no financial conflicts of interest regarding her study.

bjancin@mdedge.com

SOURCE: Kay L et al. IEC 2019, Abstract P029.

NEW YORK – Progress in understanding the sequence of events that drives vitiligo is not only behind highly promising new options for treatment, but also might be leading to a strategy that will prevent the inevitable relapse that occurs after treatment is stopped, according to an update at the American Academy of Dermatology summer meeting.

MarijaRadovic/Getty Images

Recently, trial results with a Janus kinase (JAK) pathway inhibitor have shown promise for treatment of vitiligo, but the ultimate fix for this recurring autoimmune disease might be elimination of resident-memory T cells, according to John Harris, MD, PhD, of the department of dermatology at the University of Massachusetts, Worcester.

In a murine vitiligo model, targeting interleukin-15, a cytokine thought to be essential for maintaining memory T cells, produced rapid and durable repigmentation without apparent adverse effects in a series of studies sufficiently promising that clinical trials are now being actively planned, Dr. Harris said. The ongoing work to eliminate resident-memory T cells to prevent relapse of vitiligo comes at the end of other recent advances that have provided major insights into the pathophysiology of vitiligo.

As outlined by Dr. Harris, vitiligo involves an autoimmune sequence that includes up-regulation of interferon-gamma, activation of the JAK signaling pathway, and mobilization of the cytokine CXCl10, all of which are part of the sequence of events culminating in activation of T cells that attack the melanocyte. The process can be stopped when any of these events are targeted, according to the experimental studies. These findings have already been translated into new drug development.

“There are now three ongoing clinical trials with JAK inhibitors. This is a tremendous advance in a disease for which there have been no clinical trials for decades,” Dr. Harris said. He cited highly positive data with the JAK inhibitor ruxolitinib, which were reported just weeks earlier at the World Congress of Dermatology, to confirm that this principle of intervention is viable.

However, relapse after discontinuation of ruxolitinib, like other treatments for vitiligo, is high. The observation that relapses typically occur in the exact spot where skin lesions occurred previously created the framework of a new potential wave of advances, according to Dr. Harris, director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester.

These advances involve progress in understanding the role of resident-memory T cells in driving autoimmune disease relapse.

In principle, memory-resident T cells are left behind in order to stimulate a rapid immune response in the event of a recurrence of a virus or another pathogen. According to work performed in animal models of vitiligo, they also appear to play a critical role in reactivation of this autoimmune disease, Dr. Harris said.

This role was not surprising, but the potential breakthrough in vitiligo surrounds evidence that the cytokine IL-15 is essential to the creation and maintenance of these memory cells. Evidence suggests vitiligo in animal models does not recur in the absence of IL-15, making it a potential target for treatment.

Initially, there was concern that inhibition of IL-15 would have off-target effects, but this concern has diminished with antibodies designed to inhibit IL-15 signaling in the animal model.

“It turns out that autoreactive cells are much more dependent on the cytokine than other T cells,” he said.

In the animal model, repigmentation has occurred more rapidly with anti-IL-15 therapy than with any other treatment tested to date, but more importantly, these mice then appear to be protected from vitiligo recurrence for extended periods, Dr. Harris noted.

Studies conducted with human tissue have provided strong evidence that the same mechanisms are in play. There are now several approaches to blocking IL-15 signaling, including a monoclonal antibody targeted at the IL-15 receptor, in development. This latter approach is now the focus of a company formed by Dr. Harris.

It is not yet clear if one approach to the inhibition of IL-15 will be superior to another, but Dr. Harris is highly optimistic that this will be a viable approach to control of vitiligo. Noting that good results have been achieved in experimental models by skin injections, thereby avoiding systemic exposure, he is also optimistic that this approach will be well tolerated.

“Based on these data, we are expecting clinical trials soon,” he said.

Dr. Harris reported serving as a consultant and/or investigator for multiple pharmaceutical companies including Aclaris Therapeutics, Celgene, EMD Serono, Genzyme, Incyte, and Janssen Biotech.

NEW YORK – Progress in understanding the sequence of events that drives vitiligo is not only behind highly promising new options for treatment, but also might be leading to a strategy that will prevent the inevitable relapse that occurs after treatment is stopped, according to an update at the American Academy of Dermatology summer meeting.

MarijaRadovic/Getty Images

Recently, trial results with a Janus kinase (JAK) pathway inhibitor have shown promise for treatment of vitiligo, but the ultimate fix for this recurring autoimmune disease might be elimination of resident-memory T cells, according to John Harris, MD, PhD, of the department of dermatology at the University of Massachusetts, Worcester.

In a murine vitiligo model, targeting interleukin-15, a cytokine thought to be essential for maintaining memory T cells, produced rapid and durable repigmentation without apparent adverse effects in a series of studies sufficiently promising that clinical trials are now being actively planned, Dr. Harris said. The ongoing work to eliminate resident-memory T cells to prevent relapse of vitiligo comes at the end of other recent advances that have provided major insights into the pathophysiology of vitiligo.

As outlined by Dr. Harris, vitiligo involves an autoimmune sequence that includes up-regulation of interferon-gamma, activation of the JAK signaling pathway, and mobilization of the cytokine CXCl10, all of which are part of the sequence of events culminating in activation of T cells that attack the melanocyte. The process can be stopped when any of these events are targeted, according to the experimental studies. These findings have already been translated into new drug development.

“There are now three ongoing clinical trials with JAK inhibitors. This is a tremendous advance in a disease for which there have been no clinical trials for decades,” Dr. Harris said. He cited highly positive data with the JAK inhibitor ruxolitinib, which were reported just weeks earlier at the World Congress of Dermatology, to confirm that this principle of intervention is viable.

However, relapse after discontinuation of ruxolitinib, like other treatments for vitiligo, is high. The observation that relapses typically occur in the exact spot where skin lesions occurred previously created the framework of a new potential wave of advances, according to Dr. Harris, director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester.

These advances involve progress in understanding the role of resident-memory T cells in driving autoimmune disease relapse.

In principle, memory-resident T cells are left behind in order to stimulate a rapid immune response in the event of a recurrence of a virus or another pathogen. According to work performed in animal models of vitiligo, they also appear to play a critical role in reactivation of this autoimmune disease, Dr. Harris said.

This role was not surprising, but the potential breakthrough in vitiligo surrounds evidence that the cytokine IL-15 is essential to the creation and maintenance of these memory cells. Evidence suggests vitiligo in animal models does not recur in the absence of IL-15, making it a potential target for treatment.

Initially, there was concern that inhibition of IL-15 would have off-target effects, but this concern has diminished with antibodies designed to inhibit IL-15 signaling in the animal model.

“It turns out that autoreactive cells are much more dependent on the cytokine than other T cells,” he said.

In the animal model, repigmentation has occurred more rapidly with anti-IL-15 therapy than with any other treatment tested to date, but more importantly, these mice then appear to be protected from vitiligo recurrence for extended periods, Dr. Harris noted.

Studies conducted with human tissue have provided strong evidence that the same mechanisms are in play. There are now several approaches to blocking IL-15 signaling, including a monoclonal antibody targeted at the IL-15 receptor, in development. This latter approach is now the focus of a company formed by Dr. Harris.

It is not yet clear if one approach to the inhibition of IL-15 will be superior to another, but Dr. Harris is highly optimistic that this will be a viable approach to control of vitiligo. Noting that good results have been achieved in experimental models by skin injections, thereby avoiding systemic exposure, he is also optimistic that this approach will be well tolerated.

“Based on these data, we are expecting clinical trials soon,” he said.

Dr. Harris reported serving as a consultant and/or investigator for multiple pharmaceutical companies including Aclaris Therapeutics, Celgene, EMD Serono, Genzyme, Incyte, and Janssen Biotech.

NEW YORK – Progress in understanding the sequence of events that drives vitiligo is not only behind highly promising new options for treatment, but also might be leading to a strategy that will prevent the inevitable relapse that occurs after treatment is stopped, according to an update at the American Academy of Dermatology summer meeting.

MarijaRadovic/Getty Images

Recently, trial results with a Janus kinase (JAK) pathway inhibitor have shown promise for treatment of vitiligo, but the ultimate fix for this recurring autoimmune disease might be elimination of resident-memory T cells, according to John Harris, MD, PhD, of the department of dermatology at the University of Massachusetts, Worcester.

In a murine vitiligo model, targeting interleukin-15, a cytokine thought to be essential for maintaining memory T cells, produced rapid and durable repigmentation without apparent adverse effects in a series of studies sufficiently promising that clinical trials are now being actively planned, Dr. Harris said. The ongoing work to eliminate resident-memory T cells to prevent relapse of vitiligo comes at the end of other recent advances that have provided major insights into the pathophysiology of vitiligo.

As outlined by Dr. Harris, vitiligo involves an autoimmune sequence that includes up-regulation of interferon-gamma, activation of the JAK signaling pathway, and mobilization of the cytokine CXCl10, all of which are part of the sequence of events culminating in activation of T cells that attack the melanocyte. The process can be stopped when any of these events are targeted, according to the experimental studies. These findings have already been translated into new drug development.

“There are now three ongoing clinical trials with JAK inhibitors. This is a tremendous advance in a disease for which there have been no clinical trials for decades,” Dr. Harris said. He cited highly positive data with the JAK inhibitor ruxolitinib, which were reported just weeks earlier at the World Congress of Dermatology, to confirm that this principle of intervention is viable.

However, relapse after discontinuation of ruxolitinib, like other treatments for vitiligo, is high. The observation that relapses typically occur in the exact spot where skin lesions occurred previously created the framework of a new potential wave of advances, according to Dr. Harris, director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester.

These advances involve progress in understanding the role of resident-memory T cells in driving autoimmune disease relapse.

In principle, memory-resident T cells are left behind in order to stimulate a rapid immune response in the event of a recurrence of a virus or another pathogen. According to work performed in animal models of vitiligo, they also appear to play a critical role in reactivation of this autoimmune disease, Dr. Harris said.

This role was not surprising, but the potential breakthrough in vitiligo surrounds evidence that the cytokine IL-15 is essential to the creation and maintenance of these memory cells. Evidence suggests vitiligo in animal models does not recur in the absence of IL-15, making it a potential target for treatment.

Initially, there was concern that inhibition of IL-15 would have off-target effects, but this concern has diminished with antibodies designed to inhibit IL-15 signaling in the animal model.

“It turns out that autoreactive cells are much more dependent on the cytokine than other T cells,” he said.

In the animal model, repigmentation has occurred more rapidly with anti-IL-15 therapy than with any other treatment tested to date, but more importantly, these mice then appear to be protected from vitiligo recurrence for extended periods, Dr. Harris noted.

Studies conducted with human tissue have provided strong evidence that the same mechanisms are in play. There are now several approaches to blocking IL-15 signaling, including a monoclonal antibody targeted at the IL-15 receptor, in development. This latter approach is now the focus of a company formed by Dr. Harris.

It is not yet clear if one approach to the inhibition of IL-15 will be superior to another, but Dr. Harris is highly optimistic that this will be a viable approach to control of vitiligo. Noting that good results have been achieved in experimental models by skin injections, thereby avoiding systemic exposure, he is also optimistic that this approach will be well tolerated.

“Based on these data, we are expecting clinical trials soon,” he said.

Dr. Harris reported serving as a consultant and/or investigator for multiple pharmaceutical companies including Aclaris Therapeutics, Celgene, EMD Serono, Genzyme, Incyte, and Janssen Biotech.

BANGKOK – A prediction tool that determines the risk of a pediatric epilepsy diagnosis eventually being made in a child who has had one or more paroxysmal events of possible epileptic origin is now available, and the clarity it provides makes life considerably easier for physicians and worried parents, Kees P. Braun, MD, PhD, said at the International Epilepsy Congress.

Bruce Jancin/MDedge News

This prediction tool is highly practical. It relies upon certain clinical characteristics and a first interictal EEG, all information readily available at the time of the family’s first consultation with a neurologist or pediatrician with access to EEG, noted Dr. Braun, professor of neurology at Utrecht (the Netherlands) University.

The tool is freely available online (http://epilepsypredictiontools.info/first-consultation). The details of how Dr. Braun and coinvestigators developed the prediction tool have been published (Pediatrics. 2018 Dec;142[6]:e20180931. doi: 10.1542/peds.2018-0931), he said at the congress sponsored by the International League Against Epilepsy.

Early and accurate diagnosis or exclusion of epilepsy following a suspicious paroxysmal event deserves to be a high priority. Diagnostic delay is common, with resultant unrecognized recurrent epileptic seizures that can cause cognitive and behavioral impairments. And overdiagnosis of pediatric epilepsy unnecessarily exposes a child to the risks of antiepileptic drug therapy, not to mention the potential social stigma.

The predictive tool was developed through retrospective, multidimensional analysis of detailed data on 451 children who visited the outpatient pediatric neurology clinic at University Medical Center Utrecht for a diagnostic work-up after one or more paroxysmal events that might have been seizures, all of whom were subsequently followed for a year or longer. The resultant predictive model was then independently validated in a separate cohort of 187 children seen for the same reason at another Dutch university.

The model had an area under the receiver operating characteristic curve of 0.86, which statisticians consider to be excellent discriminatory power. The tool’s sensitivity and specificity varied according to the diagnostic probability threshold selected by the parents and physicians. For example, the predictive tool had a sensitivity of 18%, specificity of 99%, positive predictive value of 94%, and negative predictive value of 80% for identification of individuals with a greater than 80% probability of being diagnosed with epilepsy. For identification of all patients with a greater than 20% likelihood of receiving the diagnosis, the sensitivity was 73%, specificity 82%, positive predictive value 76%, and negative predictive value 79%.

The clinical characteristics incorporated in the predictive model include age at first seizure, gender, details of the paroxysmal event, and specifics of the child’s medical history. The relevant features of the standard interictal EEG recorded at the time of consultation include the presence or absence of focal epileptiform abnormalities if focal spikes or spike-wave complexes were detected, generalized epileptiform abnormalities in the presence of generalized spikes or spike-wave complexes, and nonspecific nonepileptiform abnormalities.
 

Future predictive refinements are under study

Dr. Braun and coworkers have reported that examining EEG functional network characteristics – that is, the functional networks of correlated brain activity in an individual patient’s brain – improves the EEG’s predictive value for epilepsy (PLoS One. 2013;8[4]:e59764. doi: 10.1371/journal.pone.0059764), a conclusion further reinforced in their systematic review and meta-analysis incorporating 11 additional studies (PLoS One. 2014 Dec 10;9[12]:e114606. doi: 10.1371/journal.pone.0114606).

In addition, the Dutch investigators have shown that ripples superimposed on rolandic spikes seen in scalp EEG recordings have prognostic significance. An absence of ripples superimposed on rolandic spikes identified children without epilepsy. In contrast, more than five ripples predicted atypical and symptomatic rolandic epilepsy with a substantial seizure risk warranting consideration of antiepileptic drug therapy (Epilepsia. 2016 Jul;57[7]:1179-89).

A Boston group using a fully automated spike ripple detector subsequently confirmed that ripples occurring in conjunction with epileptiform discharges on scalp EEG constitute a noninvasive biomarker for seizure risk that outperforms analysis of spikes alone and could potentially be useful in guiding medication tapering decisions in children (Brain. 2019 May 1;142[5]:1296-1309).

Dr. Braun reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

BANGKOK – A prediction tool that determines the risk of a pediatric epilepsy diagnosis eventually being made in a child who has had one or more paroxysmal events of possible epileptic origin is now available, and the clarity it provides makes life considerably easier for physicians and worried parents, Kees P. Braun, MD, PhD, said at the International Epilepsy Congress.

Bruce Jancin/MDedge News

This prediction tool is highly practical. It relies upon certain clinical characteristics and a first interictal EEG, all information readily available at the time of the family’s first consultation with a neurologist or pediatrician with access to EEG, noted Dr. Braun, professor of neurology at Utrecht (the Netherlands) University.

The tool is freely available online (http://epilepsypredictiontools.info/first-consultation). The details of how Dr. Braun and coinvestigators developed the prediction tool have been published (Pediatrics. 2018 Dec;142[6]:e20180931. doi: 10.1542/peds.2018-0931), he said at the congress sponsored by the International League Against Epilepsy.

Early and accurate diagnosis or exclusion of epilepsy following a suspicious paroxysmal event deserves to be a high priority. Diagnostic delay is common, with resultant unrecognized recurrent epileptic seizures that can cause cognitive and behavioral impairments. And overdiagnosis of pediatric epilepsy unnecessarily exposes a child to the risks of antiepileptic drug therapy, not to mention the potential social stigma.

The predictive tool was developed through retrospective, multidimensional analysis of detailed data on 451 children who visited the outpatient pediatric neurology clinic at University Medical Center Utrecht for a diagnostic work-up after one or more paroxysmal events that might have been seizures, all of whom were subsequently followed for a year or longer. The resultant predictive model was then independently validated in a separate cohort of 187 children seen for the same reason at another Dutch university.

The model had an area under the receiver operating characteristic curve of 0.86, which statisticians consider to be excellent discriminatory power. The tool’s sensitivity and specificity varied according to the diagnostic probability threshold selected by the parents and physicians. For example, the predictive tool had a sensitivity of 18%, specificity of 99%, positive predictive value of 94%, and negative predictive value of 80% for identification of individuals with a greater than 80% probability of being diagnosed with epilepsy. For identification of all patients with a greater than 20% likelihood of receiving the diagnosis, the sensitivity was 73%, specificity 82%, positive predictive value 76%, and negative predictive value 79%.

The clinical characteristics incorporated in the predictive model include age at first seizure, gender, details of the paroxysmal event, and specifics of the child’s medical history. The relevant features of the standard interictal EEG recorded at the time of consultation include the presence or absence of focal epileptiform abnormalities if focal spikes or spike-wave complexes were detected, generalized epileptiform abnormalities in the presence of generalized spikes or spike-wave complexes, and nonspecific nonepileptiform abnormalities.
 

Future predictive refinements are under study

Dr. Braun and coworkers have reported that examining EEG functional network characteristics – that is, the functional networks of correlated brain activity in an individual patient’s brain – improves the EEG’s predictive value for epilepsy (PLoS One. 2013;8[4]:e59764. doi: 10.1371/journal.pone.0059764), a conclusion further reinforced in their systematic review and meta-analysis incorporating 11 additional studies (PLoS One. 2014 Dec 10;9[12]:e114606. doi: 10.1371/journal.pone.0114606).

In addition, the Dutch investigators have shown that ripples superimposed on rolandic spikes seen in scalp EEG recordings have prognostic significance. An absence of ripples superimposed on rolandic spikes identified children without epilepsy. In contrast, more than five ripples predicted atypical and symptomatic rolandic epilepsy with a substantial seizure risk warranting consideration of antiepileptic drug therapy (Epilepsia. 2016 Jul;57[7]:1179-89).

A Boston group using a fully automated spike ripple detector subsequently confirmed that ripples occurring in conjunction with epileptiform discharges on scalp EEG constitute a noninvasive biomarker for seizure risk that outperforms analysis of spikes alone and could potentially be useful in guiding medication tapering decisions in children (Brain. 2019 May 1;142[5]:1296-1309).

Dr. Braun reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

BANGKOK – A prediction tool that determines the risk of a pediatric epilepsy diagnosis eventually being made in a child who has had one or more paroxysmal events of possible epileptic origin is now available, and the clarity it provides makes life considerably easier for physicians and worried parents, Kees P. Braun, MD, PhD, said at the International Epilepsy Congress.

Bruce Jancin/MDedge News

This prediction tool is highly practical. It relies upon certain clinical characteristics and a first interictal EEG, all information readily available at the time of the family’s first consultation with a neurologist or pediatrician with access to EEG, noted Dr. Braun, professor of neurology at Utrecht (the Netherlands) University.

The tool is freely available online (http://epilepsypredictiontools.info/first-consultation). The details of how Dr. Braun and coinvestigators developed the prediction tool have been published (Pediatrics. 2018 Dec;142[6]:e20180931. doi: 10.1542/peds.2018-0931), he said at the congress sponsored by the International League Against Epilepsy.

Early and accurate diagnosis or exclusion of epilepsy following a suspicious paroxysmal event deserves to be a high priority. Diagnostic delay is common, with resultant unrecognized recurrent epileptic seizures that can cause cognitive and behavioral impairments. And overdiagnosis of pediatric epilepsy unnecessarily exposes a child to the risks of antiepileptic drug therapy, not to mention the potential social stigma.

The predictive tool was developed through retrospective, multidimensional analysis of detailed data on 451 children who visited the outpatient pediatric neurology clinic at University Medical Center Utrecht for a diagnostic work-up after one or more paroxysmal events that might have been seizures, all of whom were subsequently followed for a year or longer. The resultant predictive model was then independently validated in a separate cohort of 187 children seen for the same reason at another Dutch university.

The model had an area under the receiver operating characteristic curve of 0.86, which statisticians consider to be excellent discriminatory power. The tool’s sensitivity and specificity varied according to the diagnostic probability threshold selected by the parents and physicians. For example, the predictive tool had a sensitivity of 18%, specificity of 99%, positive predictive value of 94%, and negative predictive value of 80% for identification of individuals with a greater than 80% probability of being diagnosed with epilepsy. For identification of all patients with a greater than 20% likelihood of receiving the diagnosis, the sensitivity was 73%, specificity 82%, positive predictive value 76%, and negative predictive value 79%.

The clinical characteristics incorporated in the predictive model include age at first seizure, gender, details of the paroxysmal event, and specifics of the child’s medical history. The relevant features of the standard interictal EEG recorded at the time of consultation include the presence or absence of focal epileptiform abnormalities if focal spikes or spike-wave complexes were detected, generalized epileptiform abnormalities in the presence of generalized spikes or spike-wave complexes, and nonspecific nonepileptiform abnormalities.
 

Future predictive refinements are under study

Dr. Braun and coworkers have reported that examining EEG functional network characteristics – that is, the functional networks of correlated brain activity in an individual patient’s brain – improves the EEG’s predictive value for epilepsy (PLoS One. 2013;8[4]:e59764. doi: 10.1371/journal.pone.0059764), a conclusion further reinforced in their systematic review and meta-analysis incorporating 11 additional studies (PLoS One. 2014 Dec 10;9[12]:e114606. doi: 10.1371/journal.pone.0114606).

In addition, the Dutch investigators have shown that ripples superimposed on rolandic spikes seen in scalp EEG recordings have prognostic significance. An absence of ripples superimposed on rolandic spikes identified children without epilepsy. In contrast, more than five ripples predicted atypical and symptomatic rolandic epilepsy with a substantial seizure risk warranting consideration of antiepileptic drug therapy (Epilepsia. 2016 Jul;57[7]:1179-89).

A Boston group using a fully automated spike ripple detector subsequently confirmed that ripples occurring in conjunction with epileptiform discharges on scalp EEG constitute a noninvasive biomarker for seizure risk that outperforms analysis of spikes alone and could potentially be useful in guiding medication tapering decisions in children (Brain. 2019 May 1;142[5]:1296-1309).

Dr. Braun reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

“Smoldering” lesions—signaling chronic inflammation—may be a hallmark of more aggressive forms of multiple sclerosis (MS), according to researchers from the National Institute of Neurological Disorders and Stroke (NINDS). New technology that allows long-term in vivo monitoring could make it possible for the first time to predict who is at risk for progressive MS and potential treatments.

MS lesions appear as spots on brain scans. Some lesions heal. Others remain and may have characteristic dark rims, which is inflammatory demyelination at the edges. The dark-rimmed lesions appear to expand, or “smolder” for years. But until recently, researchers did not fully understand what role those chronic active lesions played in MS because it was difficult to find the ones that remain inflamed.

The researchers conducted 3 studies at the NIH Clinical Center. In the first, using a high-powered, 7-tesla MRI scanner and a 3D printer, they scanned the brains of 192 MS patients. Of those, 40% had no rimmed lesions; 32% had 1 to 3 rims; and 20% had ≥ 4 rims. Regardless of the treatment they were receiving, 56% of the patients had at < 1 rimmed lesion.  

The researchers compared the brain scans to the patients’ baseline neurologic examinations. Patients with ≥ 4 rimmed lesions were nearly twice as likely to be diagnosed with progressive MS than were those without rimmed lesions. Moreover, the patients with rimmed lesions developed motor and cognitive disabilities at a younger age than did patients without rimmed lesions. Patients with ≥ 4 rimmed lesions also had less white matter and smaller basal ganglia.

When they analyzed a subset of patients whose brains had been scanned once a year for ≥ 10 years, the researchers found that although the rimless lesions generally shrank, the rimmed lesions grew or stayed the same size and were “particularly damaged.”

The team also used a 3D printer to compare the spots they had seen on scans with lesions in brain tissue samples from a patient who died during the trial. All 10 expanding rimmed spots on the scans had the “telltale features” of chronic active lesions when examined under a microscope.

“Figuring out how to spot chronic active lesions was a big step,” said research team member Martina Absinta, MD, PhD. “We could not have done it without the high-powered MRI scanner.” Most MRI scanners used clinically have field strengths of 1.5 or 3 Tesla. The research team had previously published instructions for programming lower powered MRI scanners to detect rimmed chronic active lesions.

Chronic active lesions are common and exert ongoing tissue damage, said Daniel S. Reich, MD, PHD, senior investigator at NINDS, and senior author of the paper. The fact that these lesions are present in patients who are receiving anti-inflammatory drugs, he added, suggests that the field of MS research may want to focus on new treatments that target the brain’s unique immune system—especially a type of brain cell called microglia, which are instrumental in the immune response.

Their findings, the researchers say, should prompt MRI-based clinical trials aimed at treating perilesional chronic inflammation in MS. Dr. Reich said, “Our results point the way toward using specialized brain scans to predict who is at risk of developing progressive MS.”

“Smoldering” lesions—signaling chronic inflammation—may be a hallmark of more aggressive forms of multiple sclerosis (MS), according to researchers from the National Institute of Neurological Disorders and Stroke (NINDS). New technology that allows long-term in vivo monitoring could make it possible for the first time to predict who is at risk for progressive MS and potential treatments.

MS lesions appear as spots on brain scans. Some lesions heal. Others remain and may have characteristic dark rims, which is inflammatory demyelination at the edges. The dark-rimmed lesions appear to expand, or “smolder” for years. But until recently, researchers did not fully understand what role those chronic active lesions played in MS because it was difficult to find the ones that remain inflamed.

The researchers conducted 3 studies at the NIH Clinical Center. In the first, using a high-powered, 7-tesla MRI scanner and a 3D printer, they scanned the brains of 192 MS patients. Of those, 40% had no rimmed lesions; 32% had 1 to 3 rims; and 20% had ≥ 4 rims. Regardless of the treatment they were receiving, 56% of the patients had at < 1 rimmed lesion.  

The researchers compared the brain scans to the patients’ baseline neurologic examinations. Patients with ≥ 4 rimmed lesions were nearly twice as likely to be diagnosed with progressive MS than were those without rimmed lesions. Moreover, the patients with rimmed lesions developed motor and cognitive disabilities at a younger age than did patients without rimmed lesions. Patients with ≥ 4 rimmed lesions also had less white matter and smaller basal ganglia.

When they analyzed a subset of patients whose brains had been scanned once a year for ≥ 10 years, the researchers found that although the rimless lesions generally shrank, the rimmed lesions grew or stayed the same size and were “particularly damaged.”

The team also used a 3D printer to compare the spots they had seen on scans with lesions in brain tissue samples from a patient who died during the trial. All 10 expanding rimmed spots on the scans had the “telltale features” of chronic active lesions when examined under a microscope.

“Figuring out how to spot chronic active lesions was a big step,” said research team member Martina Absinta, MD, PhD. “We could not have done it without the high-powered MRI scanner.” Most MRI scanners used clinically have field strengths of 1.5 or 3 Tesla. The research team had previously published instructions for programming lower powered MRI scanners to detect rimmed chronic active lesions.

Chronic active lesions are common and exert ongoing tissue damage, said Daniel S. Reich, MD, PHD, senior investigator at NINDS, and senior author of the paper. The fact that these lesions are present in patients who are receiving anti-inflammatory drugs, he added, suggests that the field of MS research may want to focus on new treatments that target the brain’s unique immune system—especially a type of brain cell called microglia, which are instrumental in the immune response.

Their findings, the researchers say, should prompt MRI-based clinical trials aimed at treating perilesional chronic inflammation in MS. Dr. Reich said, “Our results point the way toward using specialized brain scans to predict who is at risk of developing progressive MS.”

“Smoldering” lesions—signaling chronic inflammation—may be a hallmark of more aggressive forms of multiple sclerosis (MS), according to researchers from the National Institute of Neurological Disorders and Stroke (NINDS). New technology that allows long-term in vivo monitoring could make it possible for the first time to predict who is at risk for progressive MS and potential treatments.

MS lesions appear as spots on brain scans. Some lesions heal. Others remain and may have characteristic dark rims, which is inflammatory demyelination at the edges. The dark-rimmed lesions appear to expand, or “smolder” for years. But until recently, researchers did not fully understand what role those chronic active lesions played in MS because it was difficult to find the ones that remain inflamed.

The researchers conducted 3 studies at the NIH Clinical Center. In the first, using a high-powered, 7-tesla MRI scanner and a 3D printer, they scanned the brains of 192 MS patients. Of those, 40% had no rimmed lesions; 32% had 1 to 3 rims; and 20% had ≥ 4 rims. Regardless of the treatment they were receiving, 56% of the patients had at < 1 rimmed lesion.  

The researchers compared the brain scans to the patients’ baseline neurologic examinations. Patients with ≥ 4 rimmed lesions were nearly twice as likely to be diagnosed with progressive MS than were those without rimmed lesions. Moreover, the patients with rimmed lesions developed motor and cognitive disabilities at a younger age than did patients without rimmed lesions. Patients with ≥ 4 rimmed lesions also had less white matter and smaller basal ganglia.

When they analyzed a subset of patients whose brains had been scanned once a year for ≥ 10 years, the researchers found that although the rimless lesions generally shrank, the rimmed lesions grew or stayed the same size and were “particularly damaged.”

The team also used a 3D printer to compare the spots they had seen on scans with lesions in brain tissue samples from a patient who died during the trial. All 10 expanding rimmed spots on the scans had the “telltale features” of chronic active lesions when examined under a microscope.

“Figuring out how to spot chronic active lesions was a big step,” said research team member Martina Absinta, MD, PhD. “We could not have done it without the high-powered MRI scanner.” Most MRI scanners used clinically have field strengths of 1.5 or 3 Tesla. The research team had previously published instructions for programming lower powered MRI scanners to detect rimmed chronic active lesions.

Chronic active lesions are common and exert ongoing tissue damage, said Daniel S. Reich, MD, PHD, senior investigator at NINDS, and senior author of the paper. The fact that these lesions are present in patients who are receiving anti-inflammatory drugs, he added, suggests that the field of MS research may want to focus on new treatments that target the brain’s unique immune system—especially a type of brain cell called microglia, which are instrumental in the immune response.

Their findings, the researchers say, should prompt MRI-based clinical trials aimed at treating perilesional chronic inflammation in MS. Dr. Reich said, “Our results point the way toward using specialized brain scans to predict who is at risk of developing progressive MS.”