Neurology

Multifocal microvascular injury in the brain and olfactory bulbs is another possible adverse outcome from COVID-19, new research suggests.

Postmortem MRI brain scans of 13 patients who died from COVID-19 showed abnormalities in 10 of the participants. Of these, nine showed punctate hyperintensities, “which represented areas of microvascular injury and fibrinogen leakage,” the investigators reported. Immunostaining also showed a thinning of the basal lamina in five of these patients.

Further analyses showed punctate hypointensities linked to congested blood vessels in 10 patients. These areas were “interpreted as microhemorrhages,” the researchers noted.

There was no evidence of viral infection, including SARS-CoV-2.

“These findings may inform the interpretation of changes observed on [MRI] of punctate hyperintensities and linear hypointensities in patients with COVID-19,” wrote Myoung-Hwa Lee, PhD, a research fellow at the National Institute of Neurological Disorders and Stroke, and colleagues. The findings were published online Dec. 30 in a “correspondence” piece in the New England Journal of Medicine.
 

Interpret with caution

The investigators examined brains from a convenience sample of 19 patients (mean age, 50 years), all of whom died from COVID-19 between March and July 2020.

An 11.7-tesla scanner was used to obtain magnetic resonance microscopy images for 13 of the patients. In order to scan the olfactory bulb, the scanner was set at a resolution of 25 mcm; for the brain, it was set at 100 mcm.

Chromogenic immunostaining was used to assess brain abnormalities found in 10 of the patients. Multiplex fluorescence imaging was also used for some of the patients.

For 18 study participants, a histopathological brain examination was performed. In the patients who also had medical histories available to the researchers, five had mild respiratory syndrome, four had acute respiratory distress syndrome, two had pulmonary embolism, one had delirium, and three had unknown symptoms.

The punctate hyperintensities found on magnetic resonance microscopy were also found on histopathological exam. Collagen IV immunostaining showed a thinning in the basal lamina of endothelial cells in these areas.

In addition to congested blood vessels, punctate hypointensities were linked to areas of fibrinogen leakage – but also to “relatively intact vasculature,” the investigators reported.

“There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion,” they added.

SARS-CoV-2 was also not found in any of the participants. “It is possible that the virus was cleared by the time of death or that viral copy numbers were below the level of detection by our assays,” the researchers noted.

In 13 of the patients, hypertrophic astrocytes, macrophage infiltrates, and perivascular-activated microglia were found. Eight patients showed CD3+ and CD8+ T cells in spaces and lumens next to endothelial cells.

Finally, five patients showed activated microglia next to neurons. This is “suggestive of neuronophagia in the olfactory bulb, substantial nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing,” wrote the investigators.

In summary, vascular pathology was found in 10 cases, perivascular infiltrates were present in 13 cases, acute ischemic hypoxic neurons were present in 6 cases, and changes suggestive of neuronophagia were present in 5 cases.

The researchers noted that, although the study findings may be helpful when interpreting brain changes on MRI scan in this patient population, availability of clinical information for the participants was limited.

Therefore, “no conclusions can be drawn in relation to neurologic features of COVID-19,” they wrote.

The study was funded by NINDS. Dr. Lee and all but one of the other investigators reported no relevant financial relationships; the remaining investigator reported having received grants from NINDS during the conduct of this study.

A version of this article first appeared on Medscape.com.

Multifocal microvascular injury in the brain and olfactory bulbs is another possible adverse outcome from COVID-19, new research suggests.

Postmortem MRI brain scans of 13 patients who died from COVID-19 showed abnormalities in 10 of the participants. Of these, nine showed punctate hyperintensities, “which represented areas of microvascular injury and fibrinogen leakage,” the investigators reported. Immunostaining also showed a thinning of the basal lamina in five of these patients.

Further analyses showed punctate hypointensities linked to congested blood vessels in 10 patients. These areas were “interpreted as microhemorrhages,” the researchers noted.

There was no evidence of viral infection, including SARS-CoV-2.

“These findings may inform the interpretation of changes observed on [MRI] of punctate hyperintensities and linear hypointensities in patients with COVID-19,” wrote Myoung-Hwa Lee, PhD, a research fellow at the National Institute of Neurological Disorders and Stroke, and colleagues. The findings were published online Dec. 30 in a “correspondence” piece in the New England Journal of Medicine.
 

Interpret with caution

The investigators examined brains from a convenience sample of 19 patients (mean age, 50 years), all of whom died from COVID-19 between March and July 2020.

An 11.7-tesla scanner was used to obtain magnetic resonance microscopy images for 13 of the patients. In order to scan the olfactory bulb, the scanner was set at a resolution of 25 mcm; for the brain, it was set at 100 mcm.

Chromogenic immunostaining was used to assess brain abnormalities found in 10 of the patients. Multiplex fluorescence imaging was also used for some of the patients.

For 18 study participants, a histopathological brain examination was performed. In the patients who also had medical histories available to the researchers, five had mild respiratory syndrome, four had acute respiratory distress syndrome, two had pulmonary embolism, one had delirium, and three had unknown symptoms.

The punctate hyperintensities found on magnetic resonance microscopy were also found on histopathological exam. Collagen IV immunostaining showed a thinning in the basal lamina of endothelial cells in these areas.

In addition to congested blood vessels, punctate hypointensities were linked to areas of fibrinogen leakage – but also to “relatively intact vasculature,” the investigators reported.

“There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion,” they added.

SARS-CoV-2 was also not found in any of the participants. “It is possible that the virus was cleared by the time of death or that viral copy numbers were below the level of detection by our assays,” the researchers noted.

In 13 of the patients, hypertrophic astrocytes, macrophage infiltrates, and perivascular-activated microglia were found. Eight patients showed CD3+ and CD8+ T cells in spaces and lumens next to endothelial cells.

Finally, five patients showed activated microglia next to neurons. This is “suggestive of neuronophagia in the olfactory bulb, substantial nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing,” wrote the investigators.

In summary, vascular pathology was found in 10 cases, perivascular infiltrates were present in 13 cases, acute ischemic hypoxic neurons were present in 6 cases, and changes suggestive of neuronophagia were present in 5 cases.

The researchers noted that, although the study findings may be helpful when interpreting brain changes on MRI scan in this patient population, availability of clinical information for the participants was limited.

Therefore, “no conclusions can be drawn in relation to neurologic features of COVID-19,” they wrote.

The study was funded by NINDS. Dr. Lee and all but one of the other investigators reported no relevant financial relationships; the remaining investigator reported having received grants from NINDS during the conduct of this study.

A version of this article first appeared on Medscape.com.

Multifocal microvascular injury in the brain and olfactory bulbs is another possible adverse outcome from COVID-19, new research suggests.

Postmortem MRI brain scans of 13 patients who died from COVID-19 showed abnormalities in 10 of the participants. Of these, nine showed punctate hyperintensities, “which represented areas of microvascular injury and fibrinogen leakage,” the investigators reported. Immunostaining also showed a thinning of the basal lamina in five of these patients.

Further analyses showed punctate hypointensities linked to congested blood vessels in 10 patients. These areas were “interpreted as microhemorrhages,” the researchers noted.

There was no evidence of viral infection, including SARS-CoV-2.

“These findings may inform the interpretation of changes observed on [MRI] of punctate hyperintensities and linear hypointensities in patients with COVID-19,” wrote Myoung-Hwa Lee, PhD, a research fellow at the National Institute of Neurological Disorders and Stroke, and colleagues. The findings were published online Dec. 30 in a “correspondence” piece in the New England Journal of Medicine.
 

Interpret with caution

The investigators examined brains from a convenience sample of 19 patients (mean age, 50 years), all of whom died from COVID-19 between March and July 2020.

An 11.7-tesla scanner was used to obtain magnetic resonance microscopy images for 13 of the patients. In order to scan the olfactory bulb, the scanner was set at a resolution of 25 mcm; for the brain, it was set at 100 mcm.

Chromogenic immunostaining was used to assess brain abnormalities found in 10 of the patients. Multiplex fluorescence imaging was also used for some of the patients.

For 18 study participants, a histopathological brain examination was performed. In the patients who also had medical histories available to the researchers, five had mild respiratory syndrome, four had acute respiratory distress syndrome, two had pulmonary embolism, one had delirium, and three had unknown symptoms.

The punctate hyperintensities found on magnetic resonance microscopy were also found on histopathological exam. Collagen IV immunostaining showed a thinning in the basal lamina of endothelial cells in these areas.

In addition to congested blood vessels, punctate hypointensities were linked to areas of fibrinogen leakage – but also to “relatively intact vasculature,” the investigators reported.

“There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion,” they added.

SARS-CoV-2 was also not found in any of the participants. “It is possible that the virus was cleared by the time of death or that viral copy numbers were below the level of detection by our assays,” the researchers noted.

In 13 of the patients, hypertrophic astrocytes, macrophage infiltrates, and perivascular-activated microglia were found. Eight patients showed CD3+ and CD8+ T cells in spaces and lumens next to endothelial cells.

Finally, five patients showed activated microglia next to neurons. This is “suggestive of neuronophagia in the olfactory bulb, substantial nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing,” wrote the investigators.

In summary, vascular pathology was found in 10 cases, perivascular infiltrates were present in 13 cases, acute ischemic hypoxic neurons were present in 6 cases, and changes suggestive of neuronophagia were present in 5 cases.

The researchers noted that, although the study findings may be helpful when interpreting brain changes on MRI scan in this patient population, availability of clinical information for the participants was limited.

Therefore, “no conclusions can be drawn in relation to neurologic features of COVID-19,” they wrote.

The study was funded by NINDS. Dr. Lee and all but one of the other investigators reported no relevant financial relationships; the remaining investigator reported having received grants from NINDS during the conduct of this study.

A version of this article first appeared on Medscape.com.

The expansion of the field of pediatric hospital medicine in the past 30 years has resulted in improved health care outcomes for hospitalized children^1,2 and has been accompanied by a robust increase in the amount of scholarly work related to the field.³ We performed a review of the literature published in 2019 to identify the 10 articles that had the most impact on pediatric hospital medicine, and presented the findings at HM20 Virtual, the 2020 annual conference of the Society of Hospital Medicine. Five of the selected articles are highlighted here.

STUDY 1

Wechsler ME et al. Step-up therapy in black children and adults with poorly controlled asthma. N Engl J Med. 2019 Sep 26;381(13):1227-39.

Background

Current pediatric asthma guidelines suggest adding a long-acting beta-agonist (LABA) to inhaled corticosteroid (ICS) therapy, rather than increasing the ICS dose, for children with poorly controlled asthma. However, these data are based on trials with disproportionately few Black subjects. This study aimed to determine the best step-up therapy for Black patients whose asthma was poorly controlled on ICS monotherapy.
 

Study overview and results

The authors reported two parallel double-blind, randomized, controlled trials, one in children and one in adolescents and adults. The study of children included 280 subjects ranging in age from 5 to 11, with at least one Black grandparent, and with poorly controlled asthma on low-dose ICS therapy. It used a four-way crossover design in which each subject was treated with four different 14-week treatment regimens: either double (medium-dose) or quintuple (high-dose) their baseline ICS dose, with or without the addition of a LABA. A superior response was defined by the composite outcome of at least one fewer asthma exacerbation, more asthma-control days, or a 5–percentage point difference in predicted FEV₁. Forty-six percent of children had improved asthma outcomes when the ICS dose was increased rather than with the addition of a LABA. In contrast, Black adolescents and Black adults had superior responses to the addition of a LABA. There was no significant interaction between the percentage of African ancestry as determined by DNA genotyping and the primary composite outcome. High-dose ICS was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years.
 

Limitations

Approximately 25% of children dropped out of the study, with disproportionately more children dropping out while on a high-dose ICS regimen. Additionally, the difference in the composite outcome was primarily driven by differences in FEV₁, with few subjects demonstrating a difference in asthma exacerbations or asthma-control days. Although a decrease in urinary cortisol to creatinine ratio was noted in children under 8 on high-dose ICS, the study period was not long enough to determine the clinical implications of this finding.
 

Important findings and implications

While studies with a majority of white children have suggested a superior response from adding a LABA compared to increasing the dose of an ICS, almost half of Black children showed a superior response when the dose of an ICS was increased rather than adding a LABA. It is important to note that current guidelines are based on studies with a disproportionate majority of white subjects and may not accurately reflect optimal care for patients in other racial groups. This study underscores the need to include a diverse patient population in research studies.
 

STUDY 2

Chang PW, Newman TB. A simpler prediction rule for rebound hyperbilirubinemia. Pediatrics. 2019 Jul;144(1):e20183712.

Background

Hyperbilirubinemia (jaundice) is estimated to affect 50%-60% of all newborns. Rebound hyperbilirubinemia – a rise in bilirubin after cessation of phototherapy – is common and can lead to recently discharged infants being readmitted for additional therapy. Lack of clear guidelines regarding when to discharge infants with hyperbilirubinemia has likely contributed to practice variation and some trepidation regarding whether a bilirubin level is “low enough” to discontinue therapy.
 

Study overview and results

The authors had previously proposed a three-factor hyperbilirubinemia risk model and sought to simplify their rule further.⁴ They examined a retrospective cohort of 7,048 infants greater than or equal to 35 weeks’ gestation using a random split sample. The authors derived a two-factor model using the same methods and compared its performance to the three-factor model. The two-factor formula was shown to be a good fit as a logistic regression model (Hosmer-Lemeshow test 9.21; P = .33), and the AUROC (area under the receiver operating characteristic) curves for the derivation and validation cohorts were similar between the two-factor (0.877 and 0.876, respectively) and three-factor risk models (0.887 and 0.881, respectively).
 

Limitations

These data are limited to infants receiving their first treatment of phototherapy and have not been externally validated. An important variable, serum bilirubin at phototherapy termination, was estimated in most subjects, which may have affected the accuracy of the prediction rule. Whether infants received home phototherapy was based only on equipment orders, and some infants may have received phototherapy unbeknownst to investigators. Last, infants with rebound hyperbilirubinemia at less than 72 hours after phototherapy discontinuation may have been missed.
 

Important findings and implications

This prediction model provides evidence-based, concrete data that can be used in making joint decisions with families regarding discharge timing of infants with hyperbilirubinemia. It also could be beneficial when deciding appropriate follow-up time after discharge.

STUDY 3

Ramgopal S et al. Risk of serious bacterial infection in infants aged ≤60 days presenting to emergency departments with a history of fever only. J Pediatr. 2019 Jan;204:191-195. doi: 10.1016/j.jpeds.2018.08.043.

Background

Febrile infants aged 60 days and younger are at risk for serious bacterial infections (SBI) including urinary tract infections (UTI), bacteremia, and meningitis. As physical exam is a poor discriminator of SBI in this age group, providers frequently rely on laboratory values and risk factors to guide management. Infants presenting with documented fevers by caregivers but found to have no fever in the emergency department are a challenge, and there are limited data regarding SBI frequency in this population.
 

Study overview and results

The authors performed a secondary analysis of a prospectively gathered cohort of infants aged 60 days and younger within the Pediatric Emergency Care Applied Research Network (PECARN) who had blood, urine, and CSF data available. Notable exclusions included infants who were premature, had a focal infection, were clinically ill, had recent antibiotic use, did not have blood, urine, and CSF data available, or were lost to telephone follow-up at 7 days to ensure wellness. The study cohort included 6,014 infants, 1,233 (32%) who were febrile by history alone. Rates of overall SBI were lower in the afebrile group (8.8% vs. 12.8%). For infants 0-28 days, rates of UTI were lower for the afebrile group (9.5% vs. 14.5%), but there was no difference in the rates of bacteremia or meningitis. For infants 29-60 days, rates of UTI (6.6% vs. 9.3%) and bacteremia (.5% vs. 1.7%) were lower in the afebrile group.
 

Limitations

Neither the use of home antipyretics nor the method of temperature taking at home were studied. Also, as this was a secondary analysis, it is possible that not all infants who presented with history of fever only were captured, as work-up was dictated by individual treating providers who may have chosen not to work up certain afebrile infants.
 

Important findings and implications

Nearly one-third of infants presenting for fever evaluation are afebrile on arrival. Although overall rates of SBI were lower in the group with fever by history only, this difference is largely accounted for by differing rates of UTI. Rates of bacteremia and meningitis remained substantial between groups, particularly for infants aged 0-28 days. Because of the significant morbidity associated with these infections, it is reasonable to suggest that absence of fever on presentation alone should not alter clinical or laboratory work-up, particularly in infants 0-28 days.
 

STUDY 4

Humphrey-Murto S et al. The influence of prior performance information on ratings of current performance and implications for learner handover: A scoping review. Acad Med. 2019 Jul;94(7):1050-7.

Background

Learner Handover (LH) or “forward feeding” occurs when information about trainees is shared between faculty supervisors. Although this can be helpful to tailor educational experiences and build upon previous assessments, it risks stigmatizing trainees and adding bias to future feedback and assessments as the trainee never really has a “clean slate.” In this study, the authors sought to uncover the key concepts of how prior performance information (PPI) influences assessments and any implications for medical education.
 

Study overview and results

The authors performed a cross-disciplinary scoping review looking at over 17,000 articles published between 1980 and 2017 across the domains of psychology, sports, business, and education. Seven themes were identified with the following notable findings. Raters exposed to positive PPI scored a learner’s performance higher, and vice versa. There was a dose-response relationship with more positive and more negative PPI resulting in higher and lower assessments, respectively. General standards, such as a direction to complete all work in a timely manner, caused an assimilation effect, while specific standards, such as a direction to complete a certain task by a certain day, did not. More motivated and more experienced raters are less affected by PPI, and those who believe that people can change (incremental theorists) are less affected by PPI while those who believe personal attributes are fixed (entity theorists) are more affected.
 

Limitations

The heterogeneity of the studies and the fact that they were largely conducted in experimental settings may limit generalizability to medical education. Slightly less than half of the studies included a control arm. Last, most of the studies looked at the ratings of only one target performance, not multiple performances over time.
 

Important findings and implications

Ratings of current performance displace toward PPI direction, with negative PPI more influential than positive PPI. In a formative setting, PPI may help the assessor focus on areas of possible weakness. In contrast, for a summative assessment, PPI may be prejudicial and have an impact on the rating given to the student. Clinicians should be mindful of the information they share with future raters about learners and the potential bias on future assessments that can manifest as a result.
 

STUDY 5

McCann ME et al. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): An international, multicentre, randomised, controlled equivalence trial. The Lancet. 2019 Feb;393:664-77.

Background

Animal models and observational studies have suggested a link between early anesthesia exposure and adverse neurocognitive outcomes; however, findings have been mixed and studies are prone to confounding. This study is the first randomized controlled trial to compare neurocognitive outcomes for infants exposed to general anesthesia versus awake-regional anesthesia.

Study overview and results

In this international, multicenter, assessor-masked trial, 722 infants undergoing inguinal hernia repair were randomized to awake-regional anesthesia or single-agent sevoflurane-based general anesthesia. Infants born at greater than 26 weeks’ gestational age were eligible, while those with prior anesthesia exposure or risks for neurocognitive delay were excluded. The primary outcome was full-scale intelligence quotient (FSIQ) testing at 5 years of age on the Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III). Seven additional neurodevelopmental assessments and parental questionnaires regarding behavior were administered as secondary outcomes. Average anesthesia exposure was 54 minutes and no infant had exposure greater than 120 minutes. There was no significant difference in mean scores on WPPSI-III FSIQ testing, and no difference in the additional neurocognitive assessments or parent-reported outcomes used as secondary outcomes.
 

Limitations

This study was limited to single, short periods of single-agent anesthesia exposure in children with no additional neurologic risk factors, so caution should be used in extrapolating these data to children with medical complexity and children undergoing multiple procedures, longer surgeries, or multidrug anesthetic regimens. The study population was majority male because of the surgical pathology selected and included only children in the narrow range of postmenstrual age 60 weeks or less. While this population represents a suspected a period of high cerebral vulnerability based on animal models, the implications of anesthesia exposure at other ages are unclear.
 

Important findings and implications

An estimated 10% of children from developed countries are exposed to general anesthesia during the first 3 years of life. While hospitalists do not typically select the route of anesthesia, they frequently care for patients undergoing procedures and must address parental concerns regarding the safety of anesthesia exposure. Given the rigorous study methods and long-term follow up in the current study, these data should provide reassurance that, for healthy infants undergoing short, single-agent anesthetic exposure, there is no evidence of future adverse neurologic outcomes.
 

Dr. Russo is director of pediatrics, medical director for quality and innovation, at WellSpan Health, York, Pa. Dr. Money is a pediatric hospitalist at Primary Children’s Hospital, University of Utah School of Medicine, Salt Lake City. Dr. Steed is instructor of hospital medicine, Northwestern Memorial Hospital and Ann and Robert H. Lurie Children’s Hospital of Chicago, Northwestern University School of Medicine, Chicago. The authors would like to thank Dr. Klint M. Schwenk and the Society for Hospital Medicine Pediatric Special Interest Group Executive Council.

References

1. Roberts KB, Fisher ER, and Rauch DA. The history of pediatric hospital medicine in the United States, 1996-2019. J Hosp Med. 2020 Jul;15(7):424-7.

2. Mussman GM and Conway PH. Pediatric hospitalist systems versus traditional models of care: Effect on quality and cost outcomes. J Hosp Med. 2012 Apr;7(4):350-7.

3. Wang ME, Shaughnessy EE, and Leyenaar JK. The future of pediatric hospital medicine: Challenges and opportunities. J Hosp Med. 2020 Jul;15(7):428-30.

4. Chang PW et al. A clinical prediction rule for rebound hyperbilirubinemia following inpatient phototherapy. Pediatrics. 2017;139 Mar;139(3):e20162896.

The expansion of the field of pediatric hospital medicine in the past 30 years has resulted in improved health care outcomes for hospitalized children^1,2 and has been accompanied by a robust increase in the amount of scholarly work related to the field.³ We performed a review of the literature published in 2019 to identify the 10 articles that had the most impact on pediatric hospital medicine, and presented the findings at HM20 Virtual, the 2020 annual conference of the Society of Hospital Medicine. Five of the selected articles are highlighted here.

STUDY 1

Wechsler ME et al. Step-up therapy in black children and adults with poorly controlled asthma. N Engl J Med. 2019 Sep 26;381(13):1227-39.

Background

Current pediatric asthma guidelines suggest adding a long-acting beta-agonist (LABA) to inhaled corticosteroid (ICS) therapy, rather than increasing the ICS dose, for children with poorly controlled asthma. However, these data are based on trials with disproportionately few Black subjects. This study aimed to determine the best step-up therapy for Black patients whose asthma was poorly controlled on ICS monotherapy.
 

Study overview and results

The authors reported two parallel double-blind, randomized, controlled trials, one in children and one in adolescents and adults. The study of children included 280 subjects ranging in age from 5 to 11, with at least one Black grandparent, and with poorly controlled asthma on low-dose ICS therapy. It used a four-way crossover design in which each subject was treated with four different 14-week treatment regimens: either double (medium-dose) or quintuple (high-dose) their baseline ICS dose, with or without the addition of a LABA. A superior response was defined by the composite outcome of at least one fewer asthma exacerbation, more asthma-control days, or a 5–percentage point difference in predicted FEV₁. Forty-six percent of children had improved asthma outcomes when the ICS dose was increased rather than with the addition of a LABA. In contrast, Black adolescents and Black adults had superior responses to the addition of a LABA. There was no significant interaction between the percentage of African ancestry as determined by DNA genotyping and the primary composite outcome. High-dose ICS was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years.
 

Limitations

Approximately 25% of children dropped out of the study, with disproportionately more children dropping out while on a high-dose ICS regimen. Additionally, the difference in the composite outcome was primarily driven by differences in FEV₁, with few subjects demonstrating a difference in asthma exacerbations or asthma-control days. Although a decrease in urinary cortisol to creatinine ratio was noted in children under 8 on high-dose ICS, the study period was not long enough to determine the clinical implications of this finding.
 

Important findings and implications

While studies with a majority of white children have suggested a superior response from adding a LABA compared to increasing the dose of an ICS, almost half of Black children showed a superior response when the dose of an ICS was increased rather than adding a LABA. It is important to note that current guidelines are based on studies with a disproportionate majority of white subjects and may not accurately reflect optimal care for patients in other racial groups. This study underscores the need to include a diverse patient population in research studies.
 

STUDY 2

Chang PW, Newman TB. A simpler prediction rule for rebound hyperbilirubinemia. Pediatrics. 2019 Jul;144(1):e20183712.

Background

Hyperbilirubinemia (jaundice) is estimated to affect 50%-60% of all newborns. Rebound hyperbilirubinemia – a rise in bilirubin after cessation of phototherapy – is common and can lead to recently discharged infants being readmitted for additional therapy. Lack of clear guidelines regarding when to discharge infants with hyperbilirubinemia has likely contributed to practice variation and some trepidation regarding whether a bilirubin level is “low enough” to discontinue therapy.
 

Study overview and results

The authors had previously proposed a three-factor hyperbilirubinemia risk model and sought to simplify their rule further.⁴ They examined a retrospective cohort of 7,048 infants greater than or equal to 35 weeks’ gestation using a random split sample. The authors derived a two-factor model using the same methods and compared its performance to the three-factor model. The two-factor formula was shown to be a good fit as a logistic regression model (Hosmer-Lemeshow test 9.21; P = .33), and the AUROC (area under the receiver operating characteristic) curves for the derivation and validation cohorts were similar between the two-factor (0.877 and 0.876, respectively) and three-factor risk models (0.887 and 0.881, respectively).
 

Limitations

These data are limited to infants receiving their first treatment of phototherapy and have not been externally validated. An important variable, serum bilirubin at phototherapy termination, was estimated in most subjects, which may have affected the accuracy of the prediction rule. Whether infants received home phototherapy was based only on equipment orders, and some infants may have received phototherapy unbeknownst to investigators. Last, infants with rebound hyperbilirubinemia at less than 72 hours after phototherapy discontinuation may have been missed.
 

Important findings and implications

This prediction model provides evidence-based, concrete data that can be used in making joint decisions with families regarding discharge timing of infants with hyperbilirubinemia. It also could be beneficial when deciding appropriate follow-up time after discharge.

STUDY 3

Ramgopal S et al. Risk of serious bacterial infection in infants aged ≤60 days presenting to emergency departments with a history of fever only. J Pediatr. 2019 Jan;204:191-195. doi: 10.1016/j.jpeds.2018.08.043.

Background

Febrile infants aged 60 days and younger are at risk for serious bacterial infections (SBI) including urinary tract infections (UTI), bacteremia, and meningitis. As physical exam is a poor discriminator of SBI in this age group, providers frequently rely on laboratory values and risk factors to guide management. Infants presenting with documented fevers by caregivers but found to have no fever in the emergency department are a challenge, and there are limited data regarding SBI frequency in this population.
 

Study overview and results

The authors performed a secondary analysis of a prospectively gathered cohort of infants aged 60 days and younger within the Pediatric Emergency Care Applied Research Network (PECARN) who had blood, urine, and CSF data available. Notable exclusions included infants who were premature, had a focal infection, were clinically ill, had recent antibiotic use, did not have blood, urine, and CSF data available, or were lost to telephone follow-up at 7 days to ensure wellness. The study cohort included 6,014 infants, 1,233 (32%) who were febrile by history alone. Rates of overall SBI were lower in the afebrile group (8.8% vs. 12.8%). For infants 0-28 days, rates of UTI were lower for the afebrile group (9.5% vs. 14.5%), but there was no difference in the rates of bacteremia or meningitis. For infants 29-60 days, rates of UTI (6.6% vs. 9.3%) and bacteremia (.5% vs. 1.7%) were lower in the afebrile group.
 

Limitations

Neither the use of home antipyretics nor the method of temperature taking at home were studied. Also, as this was a secondary analysis, it is possible that not all infants who presented with history of fever only were captured, as work-up was dictated by individual treating providers who may have chosen not to work up certain afebrile infants.
 

Important findings and implications

Nearly one-third of infants presenting for fever evaluation are afebrile on arrival. Although overall rates of SBI were lower in the group with fever by history only, this difference is largely accounted for by differing rates of UTI. Rates of bacteremia and meningitis remained substantial between groups, particularly for infants aged 0-28 days. Because of the significant morbidity associated with these infections, it is reasonable to suggest that absence of fever on presentation alone should not alter clinical or laboratory work-up, particularly in infants 0-28 days.
 

STUDY 4

Humphrey-Murto S et al. The influence of prior performance information on ratings of current performance and implications for learner handover: A scoping review. Acad Med. 2019 Jul;94(7):1050-7.

Background

Learner Handover (LH) or “forward feeding” occurs when information about trainees is shared between faculty supervisors. Although this can be helpful to tailor educational experiences and build upon previous assessments, it risks stigmatizing trainees and adding bias to future feedback and assessments as the trainee never really has a “clean slate.” In this study, the authors sought to uncover the key concepts of how prior performance information (PPI) influences assessments and any implications for medical education.
 

Study overview and results

The authors performed a cross-disciplinary scoping review looking at over 17,000 articles published between 1980 and 2017 across the domains of psychology, sports, business, and education. Seven themes were identified with the following notable findings. Raters exposed to positive PPI scored a learner’s performance higher, and vice versa. There was a dose-response relationship with more positive and more negative PPI resulting in higher and lower assessments, respectively. General standards, such as a direction to complete all work in a timely manner, caused an assimilation effect, while specific standards, such as a direction to complete a certain task by a certain day, did not. More motivated and more experienced raters are less affected by PPI, and those who believe that people can change (incremental theorists) are less affected by PPI while those who believe personal attributes are fixed (entity theorists) are more affected.
 

Limitations

The heterogeneity of the studies and the fact that they were largely conducted in experimental settings may limit generalizability to medical education. Slightly less than half of the studies included a control arm. Last, most of the studies looked at the ratings of only one target performance, not multiple performances over time.
 

Important findings and implications

Ratings of current performance displace toward PPI direction, with negative PPI more influential than positive PPI. In a formative setting, PPI may help the assessor focus on areas of possible weakness. In contrast, for a summative assessment, PPI may be prejudicial and have an impact on the rating given to the student. Clinicians should be mindful of the information they share with future raters about learners and the potential bias on future assessments that can manifest as a result.
 

STUDY 5

McCann ME et al. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): An international, multicentre, randomised, controlled equivalence trial. The Lancet. 2019 Feb;393:664-77.

Background

Animal models and observational studies have suggested a link between early anesthesia exposure and adverse neurocognitive outcomes; however, findings have been mixed and studies are prone to confounding. This study is the first randomized controlled trial to compare neurocognitive outcomes for infants exposed to general anesthesia versus awake-regional anesthesia.

Study overview and results

In this international, multicenter, assessor-masked trial, 722 infants undergoing inguinal hernia repair were randomized to awake-regional anesthesia or single-agent sevoflurane-based general anesthesia. Infants born at greater than 26 weeks’ gestational age were eligible, while those with prior anesthesia exposure or risks for neurocognitive delay were excluded. The primary outcome was full-scale intelligence quotient (FSIQ) testing at 5 years of age on the Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III). Seven additional neurodevelopmental assessments and parental questionnaires regarding behavior were administered as secondary outcomes. Average anesthesia exposure was 54 minutes and no infant had exposure greater than 120 minutes. There was no significant difference in mean scores on WPPSI-III FSIQ testing, and no difference in the additional neurocognitive assessments or parent-reported outcomes used as secondary outcomes.
 

Limitations

This study was limited to single, short periods of single-agent anesthesia exposure in children with no additional neurologic risk factors, so caution should be used in extrapolating these data to children with medical complexity and children undergoing multiple procedures, longer surgeries, or multidrug anesthetic regimens. The study population was majority male because of the surgical pathology selected and included only children in the narrow range of postmenstrual age 60 weeks or less. While this population represents a suspected a period of high cerebral vulnerability based on animal models, the implications of anesthesia exposure at other ages are unclear.
 

Important findings and implications

An estimated 10% of children from developed countries are exposed to general anesthesia during the first 3 years of life. While hospitalists do not typically select the route of anesthesia, they frequently care for patients undergoing procedures and must address parental concerns regarding the safety of anesthesia exposure. Given the rigorous study methods and long-term follow up in the current study, these data should provide reassurance that, for healthy infants undergoing short, single-agent anesthetic exposure, there is no evidence of future adverse neurologic outcomes.
 

Dr. Russo is director of pediatrics, medical director for quality and innovation, at WellSpan Health, York, Pa. Dr. Money is a pediatric hospitalist at Primary Children’s Hospital, University of Utah School of Medicine, Salt Lake City. Dr. Steed is instructor of hospital medicine, Northwestern Memorial Hospital and Ann and Robert H. Lurie Children’s Hospital of Chicago, Northwestern University School of Medicine, Chicago. The authors would like to thank Dr. Klint M. Schwenk and the Society for Hospital Medicine Pediatric Special Interest Group Executive Council.

References

1. Roberts KB, Fisher ER, and Rauch DA. The history of pediatric hospital medicine in the United States, 1996-2019. J Hosp Med. 2020 Jul;15(7):424-7.

2. Mussman GM and Conway PH. Pediatric hospitalist systems versus traditional models of care: Effect on quality and cost outcomes. J Hosp Med. 2012 Apr;7(4):350-7.

3. Wang ME, Shaughnessy EE, and Leyenaar JK. The future of pediatric hospital medicine: Challenges and opportunities. J Hosp Med. 2020 Jul;15(7):428-30.

4. Chang PW et al. A clinical prediction rule for rebound hyperbilirubinemia following inpatient phototherapy. Pediatrics. 2017;139 Mar;139(3):e20162896.

The expansion of the field of pediatric hospital medicine in the past 30 years has resulted in improved health care outcomes for hospitalized children^1,2 and has been accompanied by a robust increase in the amount of scholarly work related to the field.³ We performed a review of the literature published in 2019 to identify the 10 articles that had the most impact on pediatric hospital medicine, and presented the findings at HM20 Virtual, the 2020 annual conference of the Society of Hospital Medicine. Five of the selected articles are highlighted here.

STUDY 1

Wechsler ME et al. Step-up therapy in black children and adults with poorly controlled asthma. N Engl J Med. 2019 Sep 26;381(13):1227-39.

Background

Current pediatric asthma guidelines suggest adding a long-acting beta-agonist (LABA) to inhaled corticosteroid (ICS) therapy, rather than increasing the ICS dose, for children with poorly controlled asthma. However, these data are based on trials with disproportionately few Black subjects. This study aimed to determine the best step-up therapy for Black patients whose asthma was poorly controlled on ICS monotherapy.
 

Study overview and results

The authors reported two parallel double-blind, randomized, controlled trials, one in children and one in adolescents and adults. The study of children included 280 subjects ranging in age from 5 to 11, with at least one Black grandparent, and with poorly controlled asthma on low-dose ICS therapy. It used a four-way crossover design in which each subject was treated with four different 14-week treatment regimens: either double (medium-dose) or quintuple (high-dose) their baseline ICS dose, with or without the addition of a LABA. A superior response was defined by the composite outcome of at least one fewer asthma exacerbation, more asthma-control days, or a 5–percentage point difference in predicted FEV₁. Forty-six percent of children had improved asthma outcomes when the ICS dose was increased rather than with the addition of a LABA. In contrast, Black adolescents and Black adults had superior responses to the addition of a LABA. There was no significant interaction between the percentage of African ancestry as determined by DNA genotyping and the primary composite outcome. High-dose ICS was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years.
 

Limitations

Approximately 25% of children dropped out of the study, with disproportionately more children dropping out while on a high-dose ICS regimen. Additionally, the difference in the composite outcome was primarily driven by differences in FEV₁, with few subjects demonstrating a difference in asthma exacerbations or asthma-control days. Although a decrease in urinary cortisol to creatinine ratio was noted in children under 8 on high-dose ICS, the study period was not long enough to determine the clinical implications of this finding.
 

Important findings and implications

While studies with a majority of white children have suggested a superior response from adding a LABA compared to increasing the dose of an ICS, almost half of Black children showed a superior response when the dose of an ICS was increased rather than adding a LABA. It is important to note that current guidelines are based on studies with a disproportionate majority of white subjects and may not accurately reflect optimal care for patients in other racial groups. This study underscores the need to include a diverse patient population in research studies.
 

STUDY 2

Chang PW, Newman TB. A simpler prediction rule for rebound hyperbilirubinemia. Pediatrics. 2019 Jul;144(1):e20183712.

Background

Hyperbilirubinemia (jaundice) is estimated to affect 50%-60% of all newborns. Rebound hyperbilirubinemia – a rise in bilirubin after cessation of phototherapy – is common and can lead to recently discharged infants being readmitted for additional therapy. Lack of clear guidelines regarding when to discharge infants with hyperbilirubinemia has likely contributed to practice variation and some trepidation regarding whether a bilirubin level is “low enough” to discontinue therapy.
 

Study overview and results

The authors had previously proposed a three-factor hyperbilirubinemia risk model and sought to simplify their rule further.⁴ They examined a retrospective cohort of 7,048 infants greater than or equal to 35 weeks’ gestation using a random split sample. The authors derived a two-factor model using the same methods and compared its performance to the three-factor model. The two-factor formula was shown to be a good fit as a logistic regression model (Hosmer-Lemeshow test 9.21; P = .33), and the AUROC (area under the receiver operating characteristic) curves for the derivation and validation cohorts were similar between the two-factor (0.877 and 0.876, respectively) and three-factor risk models (0.887 and 0.881, respectively).
 

Limitations

These data are limited to infants receiving their first treatment of phototherapy and have not been externally validated. An important variable, serum bilirubin at phototherapy termination, was estimated in most subjects, which may have affected the accuracy of the prediction rule. Whether infants received home phototherapy was based only on equipment orders, and some infants may have received phototherapy unbeknownst to investigators. Last, infants with rebound hyperbilirubinemia at less than 72 hours after phototherapy discontinuation may have been missed.
 

Important findings and implications

This prediction model provides evidence-based, concrete data that can be used in making joint decisions with families regarding discharge timing of infants with hyperbilirubinemia. It also could be beneficial when deciding appropriate follow-up time after discharge.

STUDY 3

Ramgopal S et al. Risk of serious bacterial infection in infants aged ≤60 days presenting to emergency departments with a history of fever only. J Pediatr. 2019 Jan;204:191-195. doi: 10.1016/j.jpeds.2018.08.043.

Background

Febrile infants aged 60 days and younger are at risk for serious bacterial infections (SBI) including urinary tract infections (UTI), bacteremia, and meningitis. As physical exam is a poor discriminator of SBI in this age group, providers frequently rely on laboratory values and risk factors to guide management. Infants presenting with documented fevers by caregivers but found to have no fever in the emergency department are a challenge, and there are limited data regarding SBI frequency in this population.
 

Study overview and results

The authors performed a secondary analysis of a prospectively gathered cohort of infants aged 60 days and younger within the Pediatric Emergency Care Applied Research Network (PECARN) who had blood, urine, and CSF data available. Notable exclusions included infants who were premature, had a focal infection, were clinically ill, had recent antibiotic use, did not have blood, urine, and CSF data available, or were lost to telephone follow-up at 7 days to ensure wellness. The study cohort included 6,014 infants, 1,233 (32%) who were febrile by history alone. Rates of overall SBI were lower in the afebrile group (8.8% vs. 12.8%). For infants 0-28 days, rates of UTI were lower for the afebrile group (9.5% vs. 14.5%), but there was no difference in the rates of bacteremia or meningitis. For infants 29-60 days, rates of UTI (6.6% vs. 9.3%) and bacteremia (.5% vs. 1.7%) were lower in the afebrile group.
 

Limitations

Neither the use of home antipyretics nor the method of temperature taking at home were studied. Also, as this was a secondary analysis, it is possible that not all infants who presented with history of fever only were captured, as work-up was dictated by individual treating providers who may have chosen not to work up certain afebrile infants.
 

Important findings and implications

Nearly one-third of infants presenting for fever evaluation are afebrile on arrival. Although overall rates of SBI were lower in the group with fever by history only, this difference is largely accounted for by differing rates of UTI. Rates of bacteremia and meningitis remained substantial between groups, particularly for infants aged 0-28 days. Because of the significant morbidity associated with these infections, it is reasonable to suggest that absence of fever on presentation alone should not alter clinical or laboratory work-up, particularly in infants 0-28 days.
 

STUDY 4

Humphrey-Murto S et al. The influence of prior performance information on ratings of current performance and implications for learner handover: A scoping review. Acad Med. 2019 Jul;94(7):1050-7.

Background

Learner Handover (LH) or “forward feeding” occurs when information about trainees is shared between faculty supervisors. Although this can be helpful to tailor educational experiences and build upon previous assessments, it risks stigmatizing trainees and adding bias to future feedback and assessments as the trainee never really has a “clean slate.” In this study, the authors sought to uncover the key concepts of how prior performance information (PPI) influences assessments and any implications for medical education.
 

Study overview and results

The authors performed a cross-disciplinary scoping review looking at over 17,000 articles published between 1980 and 2017 across the domains of psychology, sports, business, and education. Seven themes were identified with the following notable findings. Raters exposed to positive PPI scored a learner’s performance higher, and vice versa. There was a dose-response relationship with more positive and more negative PPI resulting in higher and lower assessments, respectively. General standards, such as a direction to complete all work in a timely manner, caused an assimilation effect, while specific standards, such as a direction to complete a certain task by a certain day, did not. More motivated and more experienced raters are less affected by PPI, and those who believe that people can change (incremental theorists) are less affected by PPI while those who believe personal attributes are fixed (entity theorists) are more affected.
 

Limitations

The heterogeneity of the studies and the fact that they were largely conducted in experimental settings may limit generalizability to medical education. Slightly less than half of the studies included a control arm. Last, most of the studies looked at the ratings of only one target performance, not multiple performances over time.
 

Important findings and implications

Ratings of current performance displace toward PPI direction, with negative PPI more influential than positive PPI. In a formative setting, PPI may help the assessor focus on areas of possible weakness. In contrast, for a summative assessment, PPI may be prejudicial and have an impact on the rating given to the student. Clinicians should be mindful of the information they share with future raters about learners and the potential bias on future assessments that can manifest as a result.
 

STUDY 5

McCann ME et al. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): An international, multicentre, randomised, controlled equivalence trial. The Lancet. 2019 Feb;393:664-77.

Background

Animal models and observational studies have suggested a link between early anesthesia exposure and adverse neurocognitive outcomes; however, findings have been mixed and studies are prone to confounding. This study is the first randomized controlled trial to compare neurocognitive outcomes for infants exposed to general anesthesia versus awake-regional anesthesia.

Study overview and results

In this international, multicenter, assessor-masked trial, 722 infants undergoing inguinal hernia repair were randomized to awake-regional anesthesia or single-agent sevoflurane-based general anesthesia. Infants born at greater than 26 weeks’ gestational age were eligible, while those with prior anesthesia exposure or risks for neurocognitive delay were excluded. The primary outcome was full-scale intelligence quotient (FSIQ) testing at 5 years of age on the Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III). Seven additional neurodevelopmental assessments and parental questionnaires regarding behavior were administered as secondary outcomes. Average anesthesia exposure was 54 minutes and no infant had exposure greater than 120 minutes. There was no significant difference in mean scores on WPPSI-III FSIQ testing, and no difference in the additional neurocognitive assessments or parent-reported outcomes used as secondary outcomes.
 

Limitations

This study was limited to single, short periods of single-agent anesthesia exposure in children with no additional neurologic risk factors, so caution should be used in extrapolating these data to children with medical complexity and children undergoing multiple procedures, longer surgeries, or multidrug anesthetic regimens. The study population was majority male because of the surgical pathology selected and included only children in the narrow range of postmenstrual age 60 weeks or less. While this population represents a suspected a period of high cerebral vulnerability based on animal models, the implications of anesthesia exposure at other ages are unclear.
 

Important findings and implications

An estimated 10% of children from developed countries are exposed to general anesthesia during the first 3 years of life. While hospitalists do not typically select the route of anesthesia, they frequently care for patients undergoing procedures and must address parental concerns regarding the safety of anesthesia exposure. Given the rigorous study methods and long-term follow up in the current study, these data should provide reassurance that, for healthy infants undergoing short, single-agent anesthetic exposure, there is no evidence of future adverse neurologic outcomes.
 

Dr. Russo is director of pediatrics, medical director for quality and innovation, at WellSpan Health, York, Pa. Dr. Money is a pediatric hospitalist at Primary Children’s Hospital, University of Utah School of Medicine, Salt Lake City. Dr. Steed is instructor of hospital medicine, Northwestern Memorial Hospital and Ann and Robert H. Lurie Children’s Hospital of Chicago, Northwestern University School of Medicine, Chicago. The authors would like to thank Dr. Klint M. Schwenk and the Society for Hospital Medicine Pediatric Special Interest Group Executive Council.

References

1. Roberts KB, Fisher ER, and Rauch DA. The history of pediatric hospital medicine in the United States, 1996-2019. J Hosp Med. 2020 Jul;15(7):424-7.

2. Mussman GM and Conway PH. Pediatric hospitalist systems versus traditional models of care: Effect on quality and cost outcomes. J Hosp Med. 2012 Apr;7(4):350-7.

3. Wang ME, Shaughnessy EE, and Leyenaar JK. The future of pediatric hospital medicine: Challenges and opportunities. J Hosp Med. 2020 Jul;15(7):428-30.

4. Chang PW et al. A clinical prediction rule for rebound hyperbilirubinemia following inpatient phototherapy. Pediatrics. 2017;139 Mar;139(3):e20162896.

Individuals who have hypertension at any age are more likely to experience more rapid cognitive decline compared with their counterparts with normal blood pressure, new research shows. In a retrospective study of more than 15,000 participants, hypertension during middle age was associated with memory decline, and onset at later ages was linked to worsening memory and global cognition.

The investigators found that prehypertension, defined as systolic pressure of 120-139 mm Hg or diastolic pressure of 80-89 mm Hg, was also linked to accelerated cognitive decline.

Although duration of hypertension was not associated with any marker of cognitive decline, blood pressure control “can substantially reduce hypertension’s deleterious effect on the pace of cognitive decline,” said study investigator Sandhi M. Barreto, MD, PhD, professor of medicine at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

The findings were published online Dec. 14 in Hypertension.
 

Unanswered questions

Hypertension is an established and highly prevalent risk factor for cognitive decline, but the age at which it begins to affect cognition is unclear. Previous research suggests that onset during middle age is associated with more harmful cognitive effects than onset in later life. One reason for this apparent difference may be that the duration of hypertension influences the magnitude of cognitive decline, the researchers noted.

Other studies have shown that prehypertension is associated with damage to certain organs, but its effects on cognition are uncertain. In addition, the effect of good blood pressure control with antihypertensive medications and the impact on cognition are also unclear.

To investigate, the researchers examined data from the ongoing, multicenter ELSA-Brasil study. ELSA-Brasil follows 15,105 civil servants between the ages of 35 and 74 years. Dr. Barreto and team assessed data from visit 1, which was conducted between 2008 and 2010, and visit 2, which was conducted between 2012 and 2014.

At each visit, participants underwent a memory test, a verbal fluency test, and the Trail Making Test Part B. The investigators calculated Z scores for these tests to derive a global cognitive score.

Blood pressure was measured on the right arm, and hypertension status, age at the time of hypertension diagnosis, duration of hypertension diagnosis, hypertension treatment, and control status were recorded. Other covariables included sex, education, race, smoking status, physical activity, body mass index, and total cholesterol level.

The researchers excluded patients who did not undergo cognitive testing at visit 2, those who had a history of stroke at baseline, and those who initiated antihypertensive medications despite having normotension. After exclusions, the analysis included 7,063 participants (approximately 55% were women, 15% were Black).

At visit 1, the mean age of the group was 58.9 years, and 53.4% of participants had 14 or more years of education. In addition, 22% had prehypertension, and 46.8% had hypertension. The median duration of hypertension was 7 years; 29.8% of participants with hypertension were diagnosed with the condition during middle age.

Of those who reported having hypertension at visit 1, 7.3% were not taking any antihypertensive medication. Among participants with hypertension who were taking antihypertensives, 31.2% had uncontrolled blood pressure.
 

Independent predictor

Results showed that prehypertension independently predicted a significantly greater decline in verbal fluency (Z score, –0.0095; P < .01) and global cognitive score (Z score, –0.0049; P < .05) compared with normal blood pressure.

At middle age, hypertension was associated with a steeper decline in memory (Z score, –0.0072; P < .05) compared with normal blood pressure. At older ages, hypertension was linked to a steeper decline in both memory (Z score, –0.0151; P < .001) and global cognitive score (Z score, –0.0080; P < .01). Duration of hypertension, however, did not significantly predict changes in cognition (P < .109).

Among those with hypertension who were taking antihypertensive medications, those with uncontrolled blood pressure experienced greater declines in rapid memory (Z score, –0.0126; P < .01) and global cognitive score (Z score, –0.0074; P < .01) than did those with controlled blood pressure.

The investigators noted that the study participants had a comparatively high level of education, which has been shown to “boost cognitive reserve and lessen the speed of age-related cognitive decline,” Dr. Barreto said. However, “our results indicate that the effect of hypertension on cognitive decline affects individuals of all educational levels similarly,” she said.

Dr. Barreto noted that the findings have two major clinical implications. First, “maintaining blood pressure below prehypertension levels is important to preserve cognitive function or delay cognitive decline,” she said. Secondly, “in hypertensive individuals, keeping blood pressure under control is essential to reduce the speed of cognitive decline.”

The researchers plan to conduct further analyses of the data to clarify the observed relationship between memory and verbal fluency. They also plan to examine how hypertension affects long-term executive function.
 

‘Continuum of risk’

Commenting on the study, Philip B. Gorelick, MD, MPH, adjunct professor of neurology (stroke and neurocritical care) at Northwestern University, Chicago, noted that, so far, research suggests that the risk for stroke associated with blood pressure levels should be understood as representing a continuum rather than as being associated with several discrete points.

“The same may hold true for cognitive decline and dementia. There may be a continuum of risk whereby persons even at so-called elevated but relatively lower levels of blood pressure based on a continuous scale are at risk,” said Dr. Gorelick, who was not involved with the current study.

The investigators relied on a large and well-studied population of civil servants. However, the population’s relative youth and high level of education may limit the generalizability of the findings, he noted. In addition, the follow-up time was relatively short.

“The hard endpoint of dementia was not studied but would be of interest to enhance our understanding of the influence of blood pressure elevation on cognitive decline or dementia during a longer follow-up of the cohort,” Dr. Gorelick said.

The findings also suggest the need to better understand mechanisms that link blood pressure elevation with cognitive decline, he added.

They indicate “the need for additional clinical trials to better elucidate blood pressure lowering targets for cognitive preservation in different groups of persons at risk,” such as those with normal cognition, those with mild cognitive impairment, and those with dementia, said Dr. Gorelick. “For example, is it safe and efficacious to lower blood pressure in persons with more advanced cognitive impairment or dementia?” he asked.

The study was funded by the Brazilian Coordination for the Improvement of Higher Education Personnel. Dr. Barreto has received support from the Research Agency of the State of Minas Gerais. Although Dr. Gorelick was not involved in the ELSA-Brasil cohort study, he serves on a data monitoring committee for a trial of a blood pressure–lowering agent in the preservation of cognition.

A version of this article first appeared on Medscape.com.

Individuals who have hypertension at any age are more likely to experience more rapid cognitive decline compared with their counterparts with normal blood pressure, new research shows. In a retrospective study of more than 15,000 participants, hypertension during middle age was associated with memory decline, and onset at later ages was linked to worsening memory and global cognition.

The investigators found that prehypertension, defined as systolic pressure of 120-139 mm Hg or diastolic pressure of 80-89 mm Hg, was also linked to accelerated cognitive decline.

Although duration of hypertension was not associated with any marker of cognitive decline, blood pressure control “can substantially reduce hypertension’s deleterious effect on the pace of cognitive decline,” said study investigator Sandhi M. Barreto, MD, PhD, professor of medicine at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

The findings were published online Dec. 14 in Hypertension.
 

Unanswered questions

Hypertension is an established and highly prevalent risk factor for cognitive decline, but the age at which it begins to affect cognition is unclear. Previous research suggests that onset during middle age is associated with more harmful cognitive effects than onset in later life. One reason for this apparent difference may be that the duration of hypertension influences the magnitude of cognitive decline, the researchers noted.

Other studies have shown that prehypertension is associated with damage to certain organs, but its effects on cognition are uncertain. In addition, the effect of good blood pressure control with antihypertensive medications and the impact on cognition are also unclear.

To investigate, the researchers examined data from the ongoing, multicenter ELSA-Brasil study. ELSA-Brasil follows 15,105 civil servants between the ages of 35 and 74 years. Dr. Barreto and team assessed data from visit 1, which was conducted between 2008 and 2010, and visit 2, which was conducted between 2012 and 2014.

At each visit, participants underwent a memory test, a verbal fluency test, and the Trail Making Test Part B. The investigators calculated Z scores for these tests to derive a global cognitive score.

Blood pressure was measured on the right arm, and hypertension status, age at the time of hypertension diagnosis, duration of hypertension diagnosis, hypertension treatment, and control status were recorded. Other covariables included sex, education, race, smoking status, physical activity, body mass index, and total cholesterol level.

The researchers excluded patients who did not undergo cognitive testing at visit 2, those who had a history of stroke at baseline, and those who initiated antihypertensive medications despite having normotension. After exclusions, the analysis included 7,063 participants (approximately 55% were women, 15% were Black).

At visit 1, the mean age of the group was 58.9 years, and 53.4% of participants had 14 or more years of education. In addition, 22% had prehypertension, and 46.8% had hypertension. The median duration of hypertension was 7 years; 29.8% of participants with hypertension were diagnosed with the condition during middle age.

Of those who reported having hypertension at visit 1, 7.3% were not taking any antihypertensive medication. Among participants with hypertension who were taking antihypertensives, 31.2% had uncontrolled blood pressure.
 

Independent predictor

Results showed that prehypertension independently predicted a significantly greater decline in verbal fluency (Z score, –0.0095; P < .01) and global cognitive score (Z score, –0.0049; P < .05) compared with normal blood pressure.

At middle age, hypertension was associated with a steeper decline in memory (Z score, –0.0072; P < .05) compared with normal blood pressure. At older ages, hypertension was linked to a steeper decline in both memory (Z score, –0.0151; P < .001) and global cognitive score (Z score, –0.0080; P < .01). Duration of hypertension, however, did not significantly predict changes in cognition (P < .109).

Among those with hypertension who were taking antihypertensive medications, those with uncontrolled blood pressure experienced greater declines in rapid memory (Z score, –0.0126; P < .01) and global cognitive score (Z score, –0.0074; P < .01) than did those with controlled blood pressure.

The investigators noted that the study participants had a comparatively high level of education, which has been shown to “boost cognitive reserve and lessen the speed of age-related cognitive decline,” Dr. Barreto said. However, “our results indicate that the effect of hypertension on cognitive decline affects individuals of all educational levels similarly,” she said.

Dr. Barreto noted that the findings have two major clinical implications. First, “maintaining blood pressure below prehypertension levels is important to preserve cognitive function or delay cognitive decline,” she said. Secondly, “in hypertensive individuals, keeping blood pressure under control is essential to reduce the speed of cognitive decline.”

The researchers plan to conduct further analyses of the data to clarify the observed relationship between memory and verbal fluency. They also plan to examine how hypertension affects long-term executive function.
 

‘Continuum of risk’

Commenting on the study, Philip B. Gorelick, MD, MPH, adjunct professor of neurology (stroke and neurocritical care) at Northwestern University, Chicago, noted that, so far, research suggests that the risk for stroke associated with blood pressure levels should be understood as representing a continuum rather than as being associated with several discrete points.

“The same may hold true for cognitive decline and dementia. There may be a continuum of risk whereby persons even at so-called elevated but relatively lower levels of blood pressure based on a continuous scale are at risk,” said Dr. Gorelick, who was not involved with the current study.

The investigators relied on a large and well-studied population of civil servants. However, the population’s relative youth and high level of education may limit the generalizability of the findings, he noted. In addition, the follow-up time was relatively short.

“The hard endpoint of dementia was not studied but would be of interest to enhance our understanding of the influence of blood pressure elevation on cognitive decline or dementia during a longer follow-up of the cohort,” Dr. Gorelick said.

The findings also suggest the need to better understand mechanisms that link blood pressure elevation with cognitive decline, he added.

They indicate “the need for additional clinical trials to better elucidate blood pressure lowering targets for cognitive preservation in different groups of persons at risk,” such as those with normal cognition, those with mild cognitive impairment, and those with dementia, said Dr. Gorelick. “For example, is it safe and efficacious to lower blood pressure in persons with more advanced cognitive impairment or dementia?” he asked.

The study was funded by the Brazilian Coordination for the Improvement of Higher Education Personnel. Dr. Barreto has received support from the Research Agency of the State of Minas Gerais. Although Dr. Gorelick was not involved in the ELSA-Brasil cohort study, he serves on a data monitoring committee for a trial of a blood pressure–lowering agent in the preservation of cognition.

A version of this article first appeared on Medscape.com.

Individuals who have hypertension at any age are more likely to experience more rapid cognitive decline compared with their counterparts with normal blood pressure, new research shows. In a retrospective study of more than 15,000 participants, hypertension during middle age was associated with memory decline, and onset at later ages was linked to worsening memory and global cognition.

The investigators found that prehypertension, defined as systolic pressure of 120-139 mm Hg or diastolic pressure of 80-89 mm Hg, was also linked to accelerated cognitive decline.

Although duration of hypertension was not associated with any marker of cognitive decline, blood pressure control “can substantially reduce hypertension’s deleterious effect on the pace of cognitive decline,” said study investigator Sandhi M. Barreto, MD, PhD, professor of medicine at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

The findings were published online Dec. 14 in Hypertension.
 

Unanswered questions

Hypertension is an established and highly prevalent risk factor for cognitive decline, but the age at which it begins to affect cognition is unclear. Previous research suggests that onset during middle age is associated with more harmful cognitive effects than onset in later life. One reason for this apparent difference may be that the duration of hypertension influences the magnitude of cognitive decline, the researchers noted.

Other studies have shown that prehypertension is associated with damage to certain organs, but its effects on cognition are uncertain. In addition, the effect of good blood pressure control with antihypertensive medications and the impact on cognition are also unclear.

To investigate, the researchers examined data from the ongoing, multicenter ELSA-Brasil study. ELSA-Brasil follows 15,105 civil servants between the ages of 35 and 74 years. Dr. Barreto and team assessed data from visit 1, which was conducted between 2008 and 2010, and visit 2, which was conducted between 2012 and 2014.

At each visit, participants underwent a memory test, a verbal fluency test, and the Trail Making Test Part B. The investigators calculated Z scores for these tests to derive a global cognitive score.

Blood pressure was measured on the right arm, and hypertension status, age at the time of hypertension diagnosis, duration of hypertension diagnosis, hypertension treatment, and control status were recorded. Other covariables included sex, education, race, smoking status, physical activity, body mass index, and total cholesterol level.

The researchers excluded patients who did not undergo cognitive testing at visit 2, those who had a history of stroke at baseline, and those who initiated antihypertensive medications despite having normotension. After exclusions, the analysis included 7,063 participants (approximately 55% were women, 15% were Black).

At visit 1, the mean age of the group was 58.9 years, and 53.4% of participants had 14 or more years of education. In addition, 22% had prehypertension, and 46.8% had hypertension. The median duration of hypertension was 7 years; 29.8% of participants with hypertension were diagnosed with the condition during middle age.

Of those who reported having hypertension at visit 1, 7.3% were not taking any antihypertensive medication. Among participants with hypertension who were taking antihypertensives, 31.2% had uncontrolled blood pressure.
 

Independent predictor

Results showed that prehypertension independently predicted a significantly greater decline in verbal fluency (Z score, –0.0095; P < .01) and global cognitive score (Z score, –0.0049; P < .05) compared with normal blood pressure.

At middle age, hypertension was associated with a steeper decline in memory (Z score, –0.0072; P < .05) compared with normal blood pressure. At older ages, hypertension was linked to a steeper decline in both memory (Z score, –0.0151; P < .001) and global cognitive score (Z score, –0.0080; P < .01). Duration of hypertension, however, did not significantly predict changes in cognition (P < .109).

Among those with hypertension who were taking antihypertensive medications, those with uncontrolled blood pressure experienced greater declines in rapid memory (Z score, –0.0126; P < .01) and global cognitive score (Z score, –0.0074; P < .01) than did those with controlled blood pressure.

The investigators noted that the study participants had a comparatively high level of education, which has been shown to “boost cognitive reserve and lessen the speed of age-related cognitive decline,” Dr. Barreto said. However, “our results indicate that the effect of hypertension on cognitive decline affects individuals of all educational levels similarly,” she said.

Dr. Barreto noted that the findings have two major clinical implications. First, “maintaining blood pressure below prehypertension levels is important to preserve cognitive function or delay cognitive decline,” she said. Secondly, “in hypertensive individuals, keeping blood pressure under control is essential to reduce the speed of cognitive decline.”

The researchers plan to conduct further analyses of the data to clarify the observed relationship between memory and verbal fluency. They also plan to examine how hypertension affects long-term executive function.
 

‘Continuum of risk’

Commenting on the study, Philip B. Gorelick, MD, MPH, adjunct professor of neurology (stroke and neurocritical care) at Northwestern University, Chicago, noted that, so far, research suggests that the risk for stroke associated with blood pressure levels should be understood as representing a continuum rather than as being associated with several discrete points.

“The same may hold true for cognitive decline and dementia. There may be a continuum of risk whereby persons even at so-called elevated but relatively lower levels of blood pressure based on a continuous scale are at risk,” said Dr. Gorelick, who was not involved with the current study.

The investigators relied on a large and well-studied population of civil servants. However, the population’s relative youth and high level of education may limit the generalizability of the findings, he noted. In addition, the follow-up time was relatively short.

“The hard endpoint of dementia was not studied but would be of interest to enhance our understanding of the influence of blood pressure elevation on cognitive decline or dementia during a longer follow-up of the cohort,” Dr. Gorelick said.

The findings also suggest the need to better understand mechanisms that link blood pressure elevation with cognitive decline, he added.

They indicate “the need for additional clinical trials to better elucidate blood pressure lowering targets for cognitive preservation in different groups of persons at risk,” such as those with normal cognition, those with mild cognitive impairment, and those with dementia, said Dr. Gorelick. “For example, is it safe and efficacious to lower blood pressure in persons with more advanced cognitive impairment or dementia?” he asked.

The study was funded by the Brazilian Coordination for the Improvement of Higher Education Personnel. Dr. Barreto has received support from the Research Agency of the State of Minas Gerais. Although Dr. Gorelick was not involved in the ELSA-Brasil cohort study, he serves on a data monitoring committee for a trial of a blood pressure–lowering agent in the preservation of cognition.

A version of this article first appeared on Medscape.com.

Penumbra has issued an urgent recall of all configurations of the Penumbra JET 7 reperfusion catheter with Xtra Flex technology (JET 7 Xtra Flex), owing to the risk for “unexpected death or serious injury” during use for clot removal in stroke patients.

“All users should stop using this device, and facilities should remove these devices from inventory,” the recall notice, posted on the U.S. Food and Drug Administration website, advises.

The recall covers the JET 7 Xtra Flex catheter, which was cleared for use in June 2019, and the JET 7MAX configuration (which includes the JET 7 Xtra Flex catheter and MAX delivery device), which was cleared in February of this year.

The recall does not apply to the Penumbra JET 7 reperfusion catheter with standard tip.

The FDA says it has received over 200 medical device reports (MDRs) associated with the JET 7 Xtra Flex catheter, including reports of deaths, serious injuries, and malfunctions.

Twenty of these MDRs describe 14 unique patient deaths. Other MDRs describe serious patient injury, such as vessel damage, hemorrhage, and cerebral infarction.

Device malfunctions described in the reports include ballooning, expansion, rupture, breakage or complete separation, and exposure of internal support coils near the distal tip region of the JET 7 Xtra Flex catheter.

According to the FDA, bench testing by the manufacturer, in which the catheter distal tip is plugged and pressurized to failure, indicates that the JET 7 Xtra Flex catheter is not able to withstand the same burst pressures to failure as the manufacturer’s other large-bore aspiration catheters used to remove thrombus for patients with acute ischemic stroke.

Penumbra’s urgent medical device recall letter advises health care providers and facilities to remove and quarantine all unused devices covered by this recall, to complete the product identification and return form, and to return all products to Penumbra in accordance with instructions provided.

For questions regarding this recall, contact Penumbra customer service by phone at 888-272-4606 or by email at [email protected].

A version of this article first appeared on Medscape.com.

Penumbra has issued an urgent recall of all configurations of the Penumbra JET 7 reperfusion catheter with Xtra Flex technology (JET 7 Xtra Flex), owing to the risk for “unexpected death or serious injury” during use for clot removal in stroke patients.

“All users should stop using this device, and facilities should remove these devices from inventory,” the recall notice, posted on the U.S. Food and Drug Administration website, advises.

The recall covers the JET 7 Xtra Flex catheter, which was cleared for use in June 2019, and the JET 7MAX configuration (which includes the JET 7 Xtra Flex catheter and MAX delivery device), which was cleared in February of this year.

The recall does not apply to the Penumbra JET 7 reperfusion catheter with standard tip.

The FDA says it has received over 200 medical device reports (MDRs) associated with the JET 7 Xtra Flex catheter, including reports of deaths, serious injuries, and malfunctions.

Twenty of these MDRs describe 14 unique patient deaths. Other MDRs describe serious patient injury, such as vessel damage, hemorrhage, and cerebral infarction.

Device malfunctions described in the reports include ballooning, expansion, rupture, breakage or complete separation, and exposure of internal support coils near the distal tip region of the JET 7 Xtra Flex catheter.

According to the FDA, bench testing by the manufacturer, in which the catheter distal tip is plugged and pressurized to failure, indicates that the JET 7 Xtra Flex catheter is not able to withstand the same burst pressures to failure as the manufacturer’s other large-bore aspiration catheters used to remove thrombus for patients with acute ischemic stroke.

Penumbra’s urgent medical device recall letter advises health care providers and facilities to remove and quarantine all unused devices covered by this recall, to complete the product identification and return form, and to return all products to Penumbra in accordance with instructions provided.

For questions regarding this recall, contact Penumbra customer service by phone at 888-272-4606 or by email at [email protected].

A version of this article first appeared on Medscape.com.

Penumbra has issued an urgent recall of all configurations of the Penumbra JET 7 reperfusion catheter with Xtra Flex technology (JET 7 Xtra Flex), owing to the risk for “unexpected death or serious injury” during use for clot removal in stroke patients.

“All users should stop using this device, and facilities should remove these devices from inventory,” the recall notice, posted on the U.S. Food and Drug Administration website, advises.

The recall covers the JET 7 Xtra Flex catheter, which was cleared for use in June 2019, and the JET 7MAX configuration (which includes the JET 7 Xtra Flex catheter and MAX delivery device), which was cleared in February of this year.

The recall does not apply to the Penumbra JET 7 reperfusion catheter with standard tip.

The FDA says it has received over 200 medical device reports (MDRs) associated with the JET 7 Xtra Flex catheter, including reports of deaths, serious injuries, and malfunctions.

Twenty of these MDRs describe 14 unique patient deaths. Other MDRs describe serious patient injury, such as vessel damage, hemorrhage, and cerebral infarction.

Device malfunctions described in the reports include ballooning, expansion, rupture, breakage or complete separation, and exposure of internal support coils near the distal tip region of the JET 7 Xtra Flex catheter.

According to the FDA, bench testing by the manufacturer, in which the catheter distal tip is plugged and pressurized to failure, indicates that the JET 7 Xtra Flex catheter is not able to withstand the same burst pressures to failure as the manufacturer’s other large-bore aspiration catheters used to remove thrombus for patients with acute ischemic stroke.

Penumbra’s urgent medical device recall letter advises health care providers and facilities to remove and quarantine all unused devices covered by this recall, to complete the product identification and return form, and to return all products to Penumbra in accordance with instructions provided.

For questions regarding this recall, contact Penumbra customer service by phone at 888-272-4606 or by email at [email protected].

A version of this article first appeared on Medscape.com.

Serious neurologic complications in patients with COVID-19 are not limited to the severely ill, new research confirms.

“We found a range of neurologic diagnoses, including stroke and seizures, among hospitalized patients with COVID-19 and the majority were not critically ill, suggesting that these complications are not limited just to those patients who require ICU care or a ventilator,” study investigator Pria Anand, MD, division of neuro-infectious diseases, Boston University, said in an interview.

The study was published online Dec. 9 in Neurology Clinical Practice.
 

‘Moderately severe’ disability

For the study, the investigators reviewed the medical records of 74 adults (mean age, 64 years) who were hospitalized with COVID-19 and evaluated for neurologic conditions at Boston Medical Center, a safety-net hospital caring primarily for underserved, low-income, racial and ethnic minority populations.

The most common COVID-19 symptoms on arrival to the hospital were cough (39%), dyspnea (36%), and fever (34%). Eleven patients required intubation (15%) and 28 required some form of supplemental oxygen (38%). Thirty-four patients required intensive care (46%).

The most common neurologic COVID-19 symptoms at presentation were altered mental status (53%), myalgia (24%), fatigue (24%), and headache (18%). 

After neurologic assessment, the most common final neurologic diagnosis was multifactorial or toxic-metabolic encephalopathy (35%), followed by seizure (20%), ischemic stroke (20%), primary movement disorder (9%), peripheral neuropathy (8%), and hemorrhagic stroke (4%).

Three patients (4%) suffered traumatic brain injuries after falling in their homes after developing COVID-19.

Ten (14%) patients died in the hospital. Survivors had “moderately severe” disability at discharge (median modified Rankin Scale score of 4 from a preadmission mRS score of 2) and many were discharged to nursing facilities or rehabilitation hospitals.

“Although we do not have data on their posthospital course, this suggests that patients with neurologic complications of COVID-19 are likely to require ongoing rehabilitation, even after they leave the hospital,” Dr. Anand, a member of the American Academy of Neurology, said in an interview.

“There are a diverse range of mechanisms by which COVID-19 can cause neurologic complications,” Dr. Anand said.

“These complications can result from the body’s immunological response to the virus (e.g., Guillain-Barré syndrome, an autoimmune disorder affecting the nerves), from having a systemic severe illness (e.g., brain injury as a result of insufficient oxygenation), from the increased tendency to form blood clots (e.g., stroke), from worsening of preexisting neurologic disorders, and possibly from involvement of the nervous system by the virus itself,” she explained.

The researchers said more study is needed to characterize the infectious and postinfectious neurologic complications of COVID-19 in diverse patient populations.
 

Lingering issues

In an interview, Kenneth L. Tyler, MD, chair of neurology, University of Colorado, Denver, noted that this is one of the larger series published to date of the neurologic complications associated with COVID-19, and the first to come from a U.S. safety-net hospital in a large metropolitan area.

“Overall, the types and categories of neurological complications reported including encephalopathy (35%) and acute cerebrovascular events (~20%) are similar to those reported elsewhere,” said Dr. Tyler.

However, the frequency of stroke (~20%) is higher than in some other reports, “likely reflecting the comorbidities such as diabetes, hypertension, limited access to care [that are] present in this population,” he said.

Dr. Tyler also noted that the “relatively high frequency” of primary movement disorders, notably myoclonus, “hasn’t been particularly well recognized or described, although one of the authors has written on this in COVID-19, so perhaps there is a bit of an ‘ascertainment bias’ – as they were looking harder for it?”

Finally, he noted, it’s important to understand that all the published studies “vary tremendously in the populations they examine, so direct comparisons can be difficult.”

Also weighing in on the report in an interview, Richard Temes, MD, director, Northwell Health’s Center for Neurocritical Care in Manhasset, N.Y., said neurologic problems have been noted since the start of COVID-19 and have been well described.

“It’s common for patients to present with very nonspecific neurological complaints like confusion, disorientation, altered mental status, lethargy, but also neurological disease such as strokes, brain hemorrhages, and seizures are quite common as well,” said Dr. Temes. 

He also noted that a number of patients with COVID-19 will have “lingering effects, especially patients who are hospitalized, that can range from memory deficit, cognitive slowing, and trouble with activities of daily living and depression.

“These effects can occur with any patient who is hospitalized for a [significant] period of time, especially in the intensive care unit, so it’s hard to tease out whether or not this is truly from COVID itself or if it’s just being a survivor from a very severe, critical illness. We don’t know yet. We need more data on that,” he cautioned.
 

A version of this article originally appeared on Medscape.com.

Serious neurologic complications in patients with COVID-19 are not limited to the severely ill, new research confirms.

“We found a range of neurologic diagnoses, including stroke and seizures, among hospitalized patients with COVID-19 and the majority were not critically ill, suggesting that these complications are not limited just to those patients who require ICU care or a ventilator,” study investigator Pria Anand, MD, division of neuro-infectious diseases, Boston University, said in an interview.

The study was published online Dec. 9 in Neurology Clinical Practice.
 

‘Moderately severe’ disability

For the study, the investigators reviewed the medical records of 74 adults (mean age, 64 years) who were hospitalized with COVID-19 and evaluated for neurologic conditions at Boston Medical Center, a safety-net hospital caring primarily for underserved, low-income, racial and ethnic minority populations.

The most common COVID-19 symptoms on arrival to the hospital were cough (39%), dyspnea (36%), and fever (34%). Eleven patients required intubation (15%) and 28 required some form of supplemental oxygen (38%). Thirty-four patients required intensive care (46%).

The most common neurologic COVID-19 symptoms at presentation were altered mental status (53%), myalgia (24%), fatigue (24%), and headache (18%). 

After neurologic assessment, the most common final neurologic diagnosis was multifactorial or toxic-metabolic encephalopathy (35%), followed by seizure (20%), ischemic stroke (20%), primary movement disorder (9%), peripheral neuropathy (8%), and hemorrhagic stroke (4%).

Three patients (4%) suffered traumatic brain injuries after falling in their homes after developing COVID-19.

Ten (14%) patients died in the hospital. Survivors had “moderately severe” disability at discharge (median modified Rankin Scale score of 4 from a preadmission mRS score of 2) and many were discharged to nursing facilities or rehabilitation hospitals.

“Although we do not have data on their posthospital course, this suggests that patients with neurologic complications of COVID-19 are likely to require ongoing rehabilitation, even after they leave the hospital,” Dr. Anand, a member of the American Academy of Neurology, said in an interview.

“There are a diverse range of mechanisms by which COVID-19 can cause neurologic complications,” Dr. Anand said.

“These complications can result from the body’s immunological response to the virus (e.g., Guillain-Barré syndrome, an autoimmune disorder affecting the nerves), from having a systemic severe illness (e.g., brain injury as a result of insufficient oxygenation), from the increased tendency to form blood clots (e.g., stroke), from worsening of preexisting neurologic disorders, and possibly from involvement of the nervous system by the virus itself,” she explained.

The researchers said more study is needed to characterize the infectious and postinfectious neurologic complications of COVID-19 in diverse patient populations.
 

Lingering issues

In an interview, Kenneth L. Tyler, MD, chair of neurology, University of Colorado, Denver, noted that this is one of the larger series published to date of the neurologic complications associated with COVID-19, and the first to come from a U.S. safety-net hospital in a large metropolitan area.

“Overall, the types and categories of neurological complications reported including encephalopathy (35%) and acute cerebrovascular events (~20%) are similar to those reported elsewhere,” said Dr. Tyler.

However, the frequency of stroke (~20%) is higher than in some other reports, “likely reflecting the comorbidities such as diabetes, hypertension, limited access to care [that are] present in this population,” he said.

Dr. Tyler also noted that the “relatively high frequency” of primary movement disorders, notably myoclonus, “hasn’t been particularly well recognized or described, although one of the authors has written on this in COVID-19, so perhaps there is a bit of an ‘ascertainment bias’ – as they were looking harder for it?”

Finally, he noted, it’s important to understand that all the published studies “vary tremendously in the populations they examine, so direct comparisons can be difficult.”

Also weighing in on the report in an interview, Richard Temes, MD, director, Northwell Health’s Center for Neurocritical Care in Manhasset, N.Y., said neurologic problems have been noted since the start of COVID-19 and have been well described.

“It’s common for patients to present with very nonspecific neurological complaints like confusion, disorientation, altered mental status, lethargy, but also neurological disease such as strokes, brain hemorrhages, and seizures are quite common as well,” said Dr. Temes. 

He also noted that a number of patients with COVID-19 will have “lingering effects, especially patients who are hospitalized, that can range from memory deficit, cognitive slowing, and trouble with activities of daily living and depression.

“These effects can occur with any patient who is hospitalized for a [significant] period of time, especially in the intensive care unit, so it’s hard to tease out whether or not this is truly from COVID itself or if it’s just being a survivor from a very severe, critical illness. We don’t know yet. We need more data on that,” he cautioned.
 

A version of this article originally appeared on Medscape.com.

Serious neurologic complications in patients with COVID-19 are not limited to the severely ill, new research confirms.

“We found a range of neurologic diagnoses, including stroke and seizures, among hospitalized patients with COVID-19 and the majority were not critically ill, suggesting that these complications are not limited just to those patients who require ICU care or a ventilator,” study investigator Pria Anand, MD, division of neuro-infectious diseases, Boston University, said in an interview.

The study was published online Dec. 9 in Neurology Clinical Practice.
 

‘Moderately severe’ disability

For the study, the investigators reviewed the medical records of 74 adults (mean age, 64 years) who were hospitalized with COVID-19 and evaluated for neurologic conditions at Boston Medical Center, a safety-net hospital caring primarily for underserved, low-income, racial and ethnic minority populations.

The most common COVID-19 symptoms on arrival to the hospital were cough (39%), dyspnea (36%), and fever (34%). Eleven patients required intubation (15%) and 28 required some form of supplemental oxygen (38%). Thirty-four patients required intensive care (46%).

The most common neurologic COVID-19 symptoms at presentation were altered mental status (53%), myalgia (24%), fatigue (24%), and headache (18%). 

After neurologic assessment, the most common final neurologic diagnosis was multifactorial or toxic-metabolic encephalopathy (35%), followed by seizure (20%), ischemic stroke (20%), primary movement disorder (9%), peripheral neuropathy (8%), and hemorrhagic stroke (4%).

Three patients (4%) suffered traumatic brain injuries after falling in their homes after developing COVID-19.

Ten (14%) patients died in the hospital. Survivors had “moderately severe” disability at discharge (median modified Rankin Scale score of 4 from a preadmission mRS score of 2) and many were discharged to nursing facilities or rehabilitation hospitals.

“Although we do not have data on their posthospital course, this suggests that patients with neurologic complications of COVID-19 are likely to require ongoing rehabilitation, even after they leave the hospital,” Dr. Anand, a member of the American Academy of Neurology, said in an interview.

“There are a diverse range of mechanisms by which COVID-19 can cause neurologic complications,” Dr. Anand said.

“These complications can result from the body’s immunological response to the virus (e.g., Guillain-Barré syndrome, an autoimmune disorder affecting the nerves), from having a systemic severe illness (e.g., brain injury as a result of insufficient oxygenation), from the increased tendency to form blood clots (e.g., stroke), from worsening of preexisting neurologic disorders, and possibly from involvement of the nervous system by the virus itself,” she explained.

The researchers said more study is needed to characterize the infectious and postinfectious neurologic complications of COVID-19 in diverse patient populations.
 

Lingering issues

In an interview, Kenneth L. Tyler, MD, chair of neurology, University of Colorado, Denver, noted that this is one of the larger series published to date of the neurologic complications associated with COVID-19, and the first to come from a U.S. safety-net hospital in a large metropolitan area.

“Overall, the types and categories of neurological complications reported including encephalopathy (35%) and acute cerebrovascular events (~20%) are similar to those reported elsewhere,” said Dr. Tyler.

However, the frequency of stroke (~20%) is higher than in some other reports, “likely reflecting the comorbidities such as diabetes, hypertension, limited access to care [that are] present in this population,” he said.

Dr. Tyler also noted that the “relatively high frequency” of primary movement disorders, notably myoclonus, “hasn’t been particularly well recognized or described, although one of the authors has written on this in COVID-19, so perhaps there is a bit of an ‘ascertainment bias’ – as they were looking harder for it?”

Finally, he noted, it’s important to understand that all the published studies “vary tremendously in the populations they examine, so direct comparisons can be difficult.”

Also weighing in on the report in an interview, Richard Temes, MD, director, Northwell Health’s Center for Neurocritical Care in Manhasset, N.Y., said neurologic problems have been noted since the start of COVID-19 and have been well described.

“It’s common for patients to present with very nonspecific neurological complaints like confusion, disorientation, altered mental status, lethargy, but also neurological disease such as strokes, brain hemorrhages, and seizures are quite common as well,” said Dr. Temes. 

He also noted that a number of patients with COVID-19 will have “lingering effects, especially patients who are hospitalized, that can range from memory deficit, cognitive slowing, and trouble with activities of daily living and depression.

“These effects can occur with any patient who is hospitalized for a [significant] period of time, especially in the intensive care unit, so it’s hard to tease out whether or not this is truly from COVID itself or if it’s just being a survivor from a very severe, critical illness. We don’t know yet. We need more data on that,” he cautioned.
 

A version of this article originally appeared on Medscape.com.

An 11-year-old boy sought care at a small village’s health center in Panama for scalp itching and subtle hair loss. He was seen by a family physician (RU) and a team of medical students who were there as part of a humanitarian trip. The patient denied any hair pulling. He had a history of treatment for head lice.

Our physical examination revealed mild alopecia and scaling on the scalp (FIGURE 1), but what we saw through the dermatoscope (FIGURE 2) made the diagnosis clear.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Tinea capitis

On dermatoscopic examination (10× magnification), there were numerous “black dots” or broken hair shafts within patches of hair loss (FIGURE 3), which is indicative of tinea capitis.^1,2 This condition causes hair shafts to break, creating “comma hairs” and black dots. The hairs are uniform in thickness and color and bend distally, like a comma.³

Tinea capitis (commonly called ringworm of the scalp) is a fungal infection caused by Trichophyton and Microsporum dermatophytes. It is the most common pediatric dermatophyte infection in the world; the usual age of onset is 5 to 10 years.² The incidence of tinea capitis in the United States is not known because cases are no longer registered by public health agencies. That said, a Northern California study that tracked occurrences in children younger than 15 years from 1998 to 2007 found that the incidence was on the decline and lower in girls compared to boys (111.9 vs 146.4, respectively, in 1998; 27.9 vs 39.9, respectively, in 2007).⁴ Incidence rates were calculated per 10,000 eligible children.⁴

Tinea capitis can spread by contact with infected individuals and contaminated objects, including combs, towels, toys, and bedding.¹ Fungal spores can remain viable on these surfaces for months.

In a study of 69 patients with tinea capitis (23 females, 46 males; mean age, 12 years), the risk factors for spreading infection included participation in sports, contact with an animal, a recent haircut, and use of a swimming pool.⁵

4 conditions you’ll want to rule out

The following conditions should be considered as part of the differential when a patient presents with an itchy scalp and/or hair loss.

Continue to: Psoriasis of the scalp...

Psoriasis of the scalp is characterized by scaling of the scalp along with crusted plaques. It is often accompanied by similar psoriatic plaques on the elbows, knees, and other areas of the body. Examination of our patient showed no psoriatic plaques.

Seborrhea of the scalp (also known as dandruff) is a very common diagnosis. However, it is unlikely to cause hair loss. It has widespread involvement of the scalp compared to tinea capitis, which is local and patchy. Our patient’s patches of hair loss indicated that seborrhea was unlikely.

Alopecia areata. Individuals develop this condition due to an autoimmune process affecting hair follicles. However, the resulting hair loss does not cause significant scaling, inflammation, scarring, or pain in the affected area. Further, this condition can cause the loss of the entire hair shaft.

Trichotillomania is an impulse control disorder that causes patients to pull out their own hair. There is no scaling of the scalp in this condition.

A dermatoscope can beuseful in making the Dx

Although clinical appearance and patient presentation are adequate to establish the diagnosis of tinea capitis, this case demonstrates the utility of a dermatoscope in making the diagnosis of tinea capitis. Previous studies have shown that dermoscopy allows for rapid identification of the broken hair shafts, which are a key distinction from alopecia areata.^3,6

Microscopic inspection. Samples from the scaling of the scalp can be examined with potassium hydroxide (KOH) on a microscope slide. Hyphae, spores, and endo/ectothrix invasion can be seen through the microsope.  

Continue to: Laboratory testing is helpful, but not needed.

Newer antifungalsprovide a Tx advantage

Oral antifungal medications are the treatment of choice for tinea capitis. Newer antifungals, such as terbinafine and fluconazole, require a 3- to 6-week course compared to the standard 6- to 8-week course of griseofulvin.¹ Also, antifungal shampoos—such as those that contain selenium sulfide—may be used for topical treatment but only as adjuvant therapy.^1,2

For our patient, we dispensed a 3-week course of oral fluconazole, 3 to 6 mg/kg, to be given daily by his parents. We also recommended the use of an antidandruff shampoo, if possible. The treatment outcome was not known because our team’s humanitarian global health trip had ended.

An 11-year-old boy sought care at a small village’s health center in Panama for scalp itching and subtle hair loss. He was seen by a family physician (RU) and a team of medical students who were there as part of a humanitarian trip. The patient denied any hair pulling. He had a history of treatment for head lice.

Our physical examination revealed mild alopecia and scaling on the scalp (FIGURE 1), but what we saw through the dermatoscope (FIGURE 2) made the diagnosis clear.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Tinea capitis

On dermatoscopic examination (10× magnification), there were numerous “black dots” or broken hair shafts within patches of hair loss (FIGURE 3), which is indicative of tinea capitis.^1,2 This condition causes hair shafts to break, creating “comma hairs” and black dots. The hairs are uniform in thickness and color and bend distally, like a comma.³

Tinea capitis (commonly called ringworm of the scalp) is a fungal infection caused by Trichophyton and Microsporum dermatophytes. It is the most common pediatric dermatophyte infection in the world; the usual age of onset is 5 to 10 years.² The incidence of tinea capitis in the United States is not known because cases are no longer registered by public health agencies. That said, a Northern California study that tracked occurrences in children younger than 15 years from 1998 to 2007 found that the incidence was on the decline and lower in girls compared to boys (111.9 vs 146.4, respectively, in 1998; 27.9 vs 39.9, respectively, in 2007).⁴ Incidence rates were calculated per 10,000 eligible children.⁴

Tinea capitis can spread by contact with infected individuals and contaminated objects, including combs, towels, toys, and bedding.¹ Fungal spores can remain viable on these surfaces for months.

In a study of 69 patients with tinea capitis (23 females, 46 males; mean age, 12 years), the risk factors for spreading infection included participation in sports, contact with an animal, a recent haircut, and use of a swimming pool.⁵

4 conditions you’ll want to rule out

The following conditions should be considered as part of the differential when a patient presents with an itchy scalp and/or hair loss.

Continue to: Psoriasis of the scalp...

Psoriasis of the scalp is characterized by scaling of the scalp along with crusted plaques. It is often accompanied by similar psoriatic plaques on the elbows, knees, and other areas of the body. Examination of our patient showed no psoriatic plaques.

Seborrhea of the scalp (also known as dandruff) is a very common diagnosis. However, it is unlikely to cause hair loss. It has widespread involvement of the scalp compared to tinea capitis, which is local and patchy. Our patient’s patches of hair loss indicated that seborrhea was unlikely.

Alopecia areata. Individuals develop this condition due to an autoimmune process affecting hair follicles. However, the resulting hair loss does not cause significant scaling, inflammation, scarring, or pain in the affected area. Further, this condition can cause the loss of the entire hair shaft.

Trichotillomania is an impulse control disorder that causes patients to pull out their own hair. There is no scaling of the scalp in this condition.

A dermatoscope can beuseful in making the Dx

Although clinical appearance and patient presentation are adequate to establish the diagnosis of tinea capitis, this case demonstrates the utility of a dermatoscope in making the diagnosis of tinea capitis. Previous studies have shown that dermoscopy allows for rapid identification of the broken hair shafts, which are a key distinction from alopecia areata.^3,6

Microscopic inspection. Samples from the scaling of the scalp can be examined with potassium hydroxide (KOH) on a microscope slide. Hyphae, spores, and endo/ectothrix invasion can be seen through the microsope.  

Continue to: Laboratory testing is helpful, but not needed.

Newer antifungalsprovide a Tx advantage

Oral antifungal medications are the treatment of choice for tinea capitis. Newer antifungals, such as terbinafine and fluconazole, require a 3- to 6-week course compared to the standard 6- to 8-week course of griseofulvin.¹ Also, antifungal shampoos—such as those that contain selenium sulfide—may be used for topical treatment but only as adjuvant therapy.^1,2

For our patient, we dispensed a 3-week course of oral fluconazole, 3 to 6 mg/kg, to be given daily by his parents. We also recommended the use of an antidandruff shampoo, if possible. The treatment outcome was not known because our team’s humanitarian global health trip had ended.

An 11-year-old boy sought care at a small village’s health center in Panama for scalp itching and subtle hair loss. He was seen by a family physician (RU) and a team of medical students who were there as part of a humanitarian trip. The patient denied any hair pulling. He had a history of treatment for head lice.

Our physical examination revealed mild alopecia and scaling on the scalp (FIGURE 1), but what we saw through the dermatoscope (FIGURE 2) made the diagnosis clear.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Tinea capitis

On dermatoscopic examination (10× magnification), there were numerous “black dots” or broken hair shafts within patches of hair loss (FIGURE 3), which is indicative of tinea capitis.^1,2 This condition causes hair shafts to break, creating “comma hairs” and black dots. The hairs are uniform in thickness and color and bend distally, like a comma.³

Tinea capitis (commonly called ringworm of the scalp) is a fungal infection caused by Trichophyton and Microsporum dermatophytes. It is the most common pediatric dermatophyte infection in the world; the usual age of onset is 5 to 10 years.² The incidence of tinea capitis in the United States is not known because cases are no longer registered by public health agencies. That said, a Northern California study that tracked occurrences in children younger than 15 years from 1998 to 2007 found that the incidence was on the decline and lower in girls compared to boys (111.9 vs 146.4, respectively, in 1998; 27.9 vs 39.9, respectively, in 2007).⁴ Incidence rates were calculated per 10,000 eligible children.⁴

Tinea capitis can spread by contact with infected individuals and contaminated objects, including combs, towels, toys, and bedding.¹ Fungal spores can remain viable on these surfaces for months.

In a study of 69 patients with tinea capitis (23 females, 46 males; mean age, 12 years), the risk factors for spreading infection included participation in sports, contact with an animal, a recent haircut, and use of a swimming pool.⁵

4 conditions you’ll want to rule out

The following conditions should be considered as part of the differential when a patient presents with an itchy scalp and/or hair loss.

Continue to: Psoriasis of the scalp...

Psoriasis of the scalp is characterized by scaling of the scalp along with crusted plaques. It is often accompanied by similar psoriatic plaques on the elbows, knees, and other areas of the body. Examination of our patient showed no psoriatic plaques.

Seborrhea of the scalp (also known as dandruff) is a very common diagnosis. However, it is unlikely to cause hair loss. It has widespread involvement of the scalp compared to tinea capitis, which is local and patchy. Our patient’s patches of hair loss indicated that seborrhea was unlikely.

Alopecia areata. Individuals develop this condition due to an autoimmune process affecting hair follicles. However, the resulting hair loss does not cause significant scaling, inflammation, scarring, or pain in the affected area. Further, this condition can cause the loss of the entire hair shaft.

Trichotillomania is an impulse control disorder that causes patients to pull out their own hair. There is no scaling of the scalp in this condition.

A dermatoscope can beuseful in making the Dx

Although clinical appearance and patient presentation are adequate to establish the diagnosis of tinea capitis, this case demonstrates the utility of a dermatoscope in making the diagnosis of tinea capitis. Previous studies have shown that dermoscopy allows for rapid identification of the broken hair shafts, which are a key distinction from alopecia areata.^3,6

Microscopic inspection. Samples from the scaling of the scalp can be examined with potassium hydroxide (KOH) on a microscope slide. Hyphae, spores, and endo/ectothrix invasion can be seen through the microsope.  

Continue to: Laboratory testing is helpful, but not needed.

Newer antifungalsprovide a Tx advantage

Oral antifungal medications are the treatment of choice for tinea capitis. Newer antifungals, such as terbinafine and fluconazole, require a 3- to 6-week course compared to the standard 6- to 8-week course of griseofulvin.¹ Also, antifungal shampoos—such as those that contain selenium sulfide—may be used for topical treatment but only as adjuvant therapy.^1,2

For our patient, we dispensed a 3-week course of oral fluconazole, 3 to 6 mg/kg, to be given daily by his parents. We also recommended the use of an antidandruff shampoo, if possible. The treatment outcome was not known because our team’s humanitarian global health trip had ended.

Peripheral neuropathy is common in U.S. adults and is associated with an increased risk of death, even in the absence of diabetes, researchers reported  in Annals of Internal Medicine.

©mheim3011/thinkstockphotos.com

The findings do not necessarily mean that doctors should implement broader screening for peripheral neuropathy at this time, however, the investigators said.

“Doctors don’t typically screen for peripheral neuropathy in persons without diabetes,” senior author Elizabeth Selvin, PhD, MPH, professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview.

“Our study shows that peripheral neuropathy – as assessed by decreased sensation in the feet – is common, even in people without diabetes,” Dr. Selvin explained. “It is not yet clear whether we should be screening people without diabetes since we don’t have clear treatments, but our study does suggest that this condition is an underrecognized condition that is associated with poor outcomes.”

Patients with diabetes typically undergo annual foot examinations that include screening for peripheral neuropathy, but that’s not the case for most adults in the absence of diabetes.

“I don’t know if we can make the jump that we should be screening people without diabetes,” said first author Caitlin W. Hicks, MD, assistant professor of surgery, division of vascular surgery and endovascular therapy, Johns Hopkins University, Baltimore. “Right now, we do not exactly know what it means in the people without diabetes, and we definitely do not know how to treat it. So, screening for it will tell us that this person has this and is at higher risk of mortality than someone who doesn’t, but we do not know what to do with that information yet.”

Nevertheless, the study raises the question of whether physicians should pay more attention to peripheral neuropathy in people without diabetes, said Dr. Hicks, director of research at the university’s diabetic foot and wound service.
 

Heightened risk

To examine associations between peripheral neuropathy and all-cause and cardiovascular mortality in U.S. adults, Dr. Hicks and colleagues analyzed data from 7,116 adults aged 40 years or older who participated in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004.

The study included participants who underwent monofilament testing for peripheral neuropathy. During testing, technicians used a standard 5.07 Semmes-Weinstein nylon monofilament to apply slight pressure to the bottom of each foot at three sites. If participants could not correctly identify where pressure was applied, the test was repeated. After participants gave two incorrect or undeterminable responses for a site, the site was defined as insensate. The researchers defined peripheral neuropathy as at least one insensate site on either foot.

The researchers determined deaths and causes of death using death certificate records from the National Death Index through 2015.

In all, 13.5% of the participants had peripheral neuropathy, including 27% of adults with diabetes and 11.6% of adults without diabetes. Those with peripheral neuropathy were older, were more likely to be male, and had lower levels of education, compared with participants without peripheral neuropathy. They also had higher body mass index, were more often former or current smokers, and had a higher prevalence of hypertension, hypercholesterolemia, and cardiovascular disease.

During a median follow-up of 13 years, 2,128 participants died, including 488 who died of cardiovascular causes.

The incidence rate of all-cause mortality per 1,000 person-years was 57.6 in adults with diabetes and peripheral neuropathy, 34.3 in adults with peripheral neuropathy but no diabetes, 27.1 in adults with diabetes but no peripheral neuropathy, and 13.0 in adults without diabetes or peripheral neuropathy.

Among participants with diabetes, the leading cause of death was cardiovascular disease (31% of deaths), whereas among participants without diabetes, the leading cause of death was malignant neoplasms (27% of deaths).

After adjustment for age, sex, race, or ethnicity, and risk factors such as cardiovascular disease, peripheral neuropathy was significantly associated with all-cause mortality (hazard ratio [HR], 1.49) and cardiovascular mortality (HR, 1.66) in participants with diabetes. In participants without diabetes, peripheral neuropathy was significantly associated with all-cause mortality (HR, 1.31), but its association with cardiovascular mortality was not statistically significant.

The association between peripheral neuropathy and all-cause mortality persisted in a sensitivity analysis that focused on adults with normoglycemia.
 

Related conditions

The study confirms findings from prior studies that examined the prevalence of loss of peripheral sensation in populations of older adults with and without diabetes, said Elsa S. Strotmeyer, PhD, MPH, associate professor of epidemiology at the University of Pittsburgh. “The clinical significance of the loss of peripheral sensation in older adults without diabetes is not fully appreciated,” she said.

A limitation of the study is that peripheral neuropathy was not a clinical diagnosis. “Monofilament testing at the foot is a quick clinical screen for decreased lower-extremity sensation that likely is a result of sensory peripheral nerve decline,” Dr. Strotmeyer said.

Another limitation is that death certificates are less accurate than medical records for determining cause of death.

“Past studies have indicated that peripheral nerve decline is related to common conditions in aging such as the metabolic syndrome and cardiovascular disease, cancer treatment, and physical function loss,” Dr. Strotmeyer said. “Therefore it is not surprising that is related to mortality as these conditions in aging are associated with increased mortality. Loss of peripheral sensation at the foot may also be related to fall injuries, and mortality from fall injuries has increased dramatically in older adults over the past several decades.”

Prior research has suggested that monofilament testing may play a role in screening for fall risk in older adults without diabetes, Dr. Strotmeyer added.

“For older adults both with and without diabetes, past studies have recommended monofilament testing be incorporated in geriatric screening for fall risk. Therefore, this article expands implications of clinical importance to understanding the pathology and consequences of loss of sensation at the foot in older patients,” she said.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute. Dr. Hicks, Dr. Selvin, and a coauthor, Kunihiro Matsushita, MD, PhD, disclosed NIH grants. In addition, Dr. Selvin disclosed personal fees from Novo Nordisk and grants from the Foundation for the National Institutes of Health outside the submitted work, and Dr. Matsushita disclosed grants and personal fees from Fukuda Denshi outside the submitted work. Dr. Strotmeyer receives funding from the National Institute on Aging and the National Institute of Arthritis and Musculoskeletal and Skin Diseases and is chair of the health sciences section of the Gerontological Society of America.

A version of this article originally appeared on Medscape.com.

Peripheral neuropathy is common in U.S. adults and is associated with an increased risk of death, even in the absence of diabetes, researchers reported  in Annals of Internal Medicine.

©mheim3011/thinkstockphotos.com

The findings do not necessarily mean that doctors should implement broader screening for peripheral neuropathy at this time, however, the investigators said.

“Doctors don’t typically screen for peripheral neuropathy in persons without diabetes,” senior author Elizabeth Selvin, PhD, MPH, professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview.

“Our study shows that peripheral neuropathy – as assessed by decreased sensation in the feet – is common, even in people without diabetes,” Dr. Selvin explained. “It is not yet clear whether we should be screening people without diabetes since we don’t have clear treatments, but our study does suggest that this condition is an underrecognized condition that is associated with poor outcomes.”

Patients with diabetes typically undergo annual foot examinations that include screening for peripheral neuropathy, but that’s not the case for most adults in the absence of diabetes.

“I don’t know if we can make the jump that we should be screening people without diabetes,” said first author Caitlin W. Hicks, MD, assistant professor of surgery, division of vascular surgery and endovascular therapy, Johns Hopkins University, Baltimore. “Right now, we do not exactly know what it means in the people without diabetes, and we definitely do not know how to treat it. So, screening for it will tell us that this person has this and is at higher risk of mortality than someone who doesn’t, but we do not know what to do with that information yet.”

Nevertheless, the study raises the question of whether physicians should pay more attention to peripheral neuropathy in people without diabetes, said Dr. Hicks, director of research at the university’s diabetic foot and wound service.
 

Heightened risk

To examine associations between peripheral neuropathy and all-cause and cardiovascular mortality in U.S. adults, Dr. Hicks and colleagues analyzed data from 7,116 adults aged 40 years or older who participated in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004.

The study included participants who underwent monofilament testing for peripheral neuropathy. During testing, technicians used a standard 5.07 Semmes-Weinstein nylon monofilament to apply slight pressure to the bottom of each foot at three sites. If participants could not correctly identify where pressure was applied, the test was repeated. After participants gave two incorrect or undeterminable responses for a site, the site was defined as insensate. The researchers defined peripheral neuropathy as at least one insensate site on either foot.

The researchers determined deaths and causes of death using death certificate records from the National Death Index through 2015.

In all, 13.5% of the participants had peripheral neuropathy, including 27% of adults with diabetes and 11.6% of adults without diabetes. Those with peripheral neuropathy were older, were more likely to be male, and had lower levels of education, compared with participants without peripheral neuropathy. They also had higher body mass index, were more often former or current smokers, and had a higher prevalence of hypertension, hypercholesterolemia, and cardiovascular disease.

During a median follow-up of 13 years, 2,128 participants died, including 488 who died of cardiovascular causes.

The incidence rate of all-cause mortality per 1,000 person-years was 57.6 in adults with diabetes and peripheral neuropathy, 34.3 in adults with peripheral neuropathy but no diabetes, 27.1 in adults with diabetes but no peripheral neuropathy, and 13.0 in adults without diabetes or peripheral neuropathy.

Among participants with diabetes, the leading cause of death was cardiovascular disease (31% of deaths), whereas among participants without diabetes, the leading cause of death was malignant neoplasms (27% of deaths).

After adjustment for age, sex, race, or ethnicity, and risk factors such as cardiovascular disease, peripheral neuropathy was significantly associated with all-cause mortality (hazard ratio [HR], 1.49) and cardiovascular mortality (HR, 1.66) in participants with diabetes. In participants without diabetes, peripheral neuropathy was significantly associated with all-cause mortality (HR, 1.31), but its association with cardiovascular mortality was not statistically significant.

The association between peripheral neuropathy and all-cause mortality persisted in a sensitivity analysis that focused on adults with normoglycemia.
 

Related conditions

The study confirms findings from prior studies that examined the prevalence of loss of peripheral sensation in populations of older adults with and without diabetes, said Elsa S. Strotmeyer, PhD, MPH, associate professor of epidemiology at the University of Pittsburgh. “The clinical significance of the loss of peripheral sensation in older adults without diabetes is not fully appreciated,” she said.

A limitation of the study is that peripheral neuropathy was not a clinical diagnosis. “Monofilament testing at the foot is a quick clinical screen for decreased lower-extremity sensation that likely is a result of sensory peripheral nerve decline,” Dr. Strotmeyer said.

Another limitation is that death certificates are less accurate than medical records for determining cause of death.

“Past studies have indicated that peripheral nerve decline is related to common conditions in aging such as the metabolic syndrome and cardiovascular disease, cancer treatment, and physical function loss,” Dr. Strotmeyer said. “Therefore it is not surprising that is related to mortality as these conditions in aging are associated with increased mortality. Loss of peripheral sensation at the foot may also be related to fall injuries, and mortality from fall injuries has increased dramatically in older adults over the past several decades.”

Prior research has suggested that monofilament testing may play a role in screening for fall risk in older adults without diabetes, Dr. Strotmeyer added.

“For older adults both with and without diabetes, past studies have recommended monofilament testing be incorporated in geriatric screening for fall risk. Therefore, this article expands implications of clinical importance to understanding the pathology and consequences of loss of sensation at the foot in older patients,” she said.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute. Dr. Hicks, Dr. Selvin, and a coauthor, Kunihiro Matsushita, MD, PhD, disclosed NIH grants. In addition, Dr. Selvin disclosed personal fees from Novo Nordisk and grants from the Foundation for the National Institutes of Health outside the submitted work, and Dr. Matsushita disclosed grants and personal fees from Fukuda Denshi outside the submitted work. Dr. Strotmeyer receives funding from the National Institute on Aging and the National Institute of Arthritis and Musculoskeletal and Skin Diseases and is chair of the health sciences section of the Gerontological Society of America.

A version of this article originally appeared on Medscape.com.

Peripheral neuropathy is common in U.S. adults and is associated with an increased risk of death, even in the absence of diabetes, researchers reported  in Annals of Internal Medicine.

©mheim3011/thinkstockphotos.com

The findings do not necessarily mean that doctors should implement broader screening for peripheral neuropathy at this time, however, the investigators said.

“Doctors don’t typically screen for peripheral neuropathy in persons without diabetes,” senior author Elizabeth Selvin, PhD, MPH, professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview.

“Our study shows that peripheral neuropathy – as assessed by decreased sensation in the feet – is common, even in people without diabetes,” Dr. Selvin explained. “It is not yet clear whether we should be screening people without diabetes since we don’t have clear treatments, but our study does suggest that this condition is an underrecognized condition that is associated with poor outcomes.”

Patients with diabetes typically undergo annual foot examinations that include screening for peripheral neuropathy, but that’s not the case for most adults in the absence of diabetes.

“I don’t know if we can make the jump that we should be screening people without diabetes,” said first author Caitlin W. Hicks, MD, assistant professor of surgery, division of vascular surgery and endovascular therapy, Johns Hopkins University, Baltimore. “Right now, we do not exactly know what it means in the people without diabetes, and we definitely do not know how to treat it. So, screening for it will tell us that this person has this and is at higher risk of mortality than someone who doesn’t, but we do not know what to do with that information yet.”

Nevertheless, the study raises the question of whether physicians should pay more attention to peripheral neuropathy in people without diabetes, said Dr. Hicks, director of research at the university’s diabetic foot and wound service.
 

Heightened risk

To examine associations between peripheral neuropathy and all-cause and cardiovascular mortality in U.S. adults, Dr. Hicks and colleagues analyzed data from 7,116 adults aged 40 years or older who participated in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004.

The study included participants who underwent monofilament testing for peripheral neuropathy. During testing, technicians used a standard 5.07 Semmes-Weinstein nylon monofilament to apply slight pressure to the bottom of each foot at three sites. If participants could not correctly identify where pressure was applied, the test was repeated. After participants gave two incorrect or undeterminable responses for a site, the site was defined as insensate. The researchers defined peripheral neuropathy as at least one insensate site on either foot.

The researchers determined deaths and causes of death using death certificate records from the National Death Index through 2015.

In all, 13.5% of the participants had peripheral neuropathy, including 27% of adults with diabetes and 11.6% of adults without diabetes. Those with peripheral neuropathy were older, were more likely to be male, and had lower levels of education, compared with participants without peripheral neuropathy. They also had higher body mass index, were more often former or current smokers, and had a higher prevalence of hypertension, hypercholesterolemia, and cardiovascular disease.

During a median follow-up of 13 years, 2,128 participants died, including 488 who died of cardiovascular causes.

The incidence rate of all-cause mortality per 1,000 person-years was 57.6 in adults with diabetes and peripheral neuropathy, 34.3 in adults with peripheral neuropathy but no diabetes, 27.1 in adults with diabetes but no peripheral neuropathy, and 13.0 in adults without diabetes or peripheral neuropathy.

Among participants with diabetes, the leading cause of death was cardiovascular disease (31% of deaths), whereas among participants without diabetes, the leading cause of death was malignant neoplasms (27% of deaths).

After adjustment for age, sex, race, or ethnicity, and risk factors such as cardiovascular disease, peripheral neuropathy was significantly associated with all-cause mortality (hazard ratio [HR], 1.49) and cardiovascular mortality (HR, 1.66) in participants with diabetes. In participants without diabetes, peripheral neuropathy was significantly associated with all-cause mortality (HR, 1.31), but its association with cardiovascular mortality was not statistically significant.

The association between peripheral neuropathy and all-cause mortality persisted in a sensitivity analysis that focused on adults with normoglycemia.
 

Related conditions

The study confirms findings from prior studies that examined the prevalence of loss of peripheral sensation in populations of older adults with and without diabetes, said Elsa S. Strotmeyer, PhD, MPH, associate professor of epidemiology at the University of Pittsburgh. “The clinical significance of the loss of peripheral sensation in older adults without diabetes is not fully appreciated,” she said.

A limitation of the study is that peripheral neuropathy was not a clinical diagnosis. “Monofilament testing at the foot is a quick clinical screen for decreased lower-extremity sensation that likely is a result of sensory peripheral nerve decline,” Dr. Strotmeyer said.

Another limitation is that death certificates are less accurate than medical records for determining cause of death.

“Past studies have indicated that peripheral nerve decline is related to common conditions in aging such as the metabolic syndrome and cardiovascular disease, cancer treatment, and physical function loss,” Dr. Strotmeyer said. “Therefore it is not surprising that is related to mortality as these conditions in aging are associated with increased mortality. Loss of peripheral sensation at the foot may also be related to fall injuries, and mortality from fall injuries has increased dramatically in older adults over the past several decades.”

Prior research has suggested that monofilament testing may play a role in screening for fall risk in older adults without diabetes, Dr. Strotmeyer added.

“For older adults both with and without diabetes, past studies have recommended monofilament testing be incorporated in geriatric screening for fall risk. Therefore, this article expands implications of clinical importance to understanding the pathology and consequences of loss of sensation at the foot in older patients,” she said.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute. Dr. Hicks, Dr. Selvin, and a coauthor, Kunihiro Matsushita, MD, PhD, disclosed NIH grants. In addition, Dr. Selvin disclosed personal fees from Novo Nordisk and grants from the Foundation for the National Institutes of Health outside the submitted work, and Dr. Matsushita disclosed grants and personal fees from Fukuda Denshi outside the submitted work. Dr. Strotmeyer receives funding from the National Institute on Aging and the National Institute of Arthritis and Musculoskeletal and Skin Diseases and is chair of the health sciences section of the Gerontological Society of America.

A version of this article originally appeared on Medscape.com.

A new type of laser therapy is safe and effective for children with drug-resistant epilepsy, new research suggests. In a study of nearly 150 children, more than half of those who received MRI-guided laser interstitial thermal therapy (MRgLITT) were seizure free at 1 year.

Results show that this “is a new and promising therapy” for children for whom drug therapy has failed, said study investigator Elysa Widjaja, MD, a pediatric neuroradiologist at the Hospital for Sick Children and professor in the department of medical imaging, University of Toronto.

In addition, the procedure is less invasive and requires a shorter hospital stay than does open epilepsy surgery, Dr. Widjaja said.

The findings were presented at the annual meeting of the American Epilepsy Society, which was held online this year because of the COVID-19 pandemic.
 

Registry study

To date, most published studies on the laser procedure have had a small number of participants from only a few centers, Dr. Widjaja noted. “The aim of our registry is to collect data from multiple centers in both Canada and the U.S. to try to get a better understanding of the outcomes following laser therapy and the complications associated with this treatment,” she said.

In the procedure, a surgeon drills a tiny hole through the skull and, guided by MRI, inserts a very thin laser fiber into the center of the lesion. Heat then ablates the affected brain region.

From the dedicated registry, researchers recruited 182 children who were treated with MRgLITT at seven pediatric centers in the United States and two centers in Canada. The youngest patient was aged 14 months, and the oldest was aged 21 years (mean age, 11.2 years). Some pediatric hospitals treat patients up to age 21, Dr. Widjaja noted.

All of the study participants had focal epilepsy, “so the seizures are coming from a defined area of the brain,” she added. In addition, study participants’ conditions were drug-resistant, defined as conditions in which two antiseizure medications had previously failed.

The mean age at seizure onset was 5.4 years, and the mean number of antiepileptic drugs that were taken was 2.3.

Before receiving the therapy, children typically undergo extensive analyses, including MRI and video electroencephalography, to pinpoint where in the brain the seizures originate. Dr. Widjaja noted that the specific area of the brain that is affected varies widely from child to child.

The investigators collected baseline clinical characteristic and procedural data, including ablation site, type of lesion, length of stay, complications, number of MRgLITT procedures, and seizure outcome. To gather this information, they used a secure electronic platform designed to collect and store research data.
 

Seizure freedom

Among 137 patients for whom 1-year seizure outcomes were available, seizure freedom was reported for 74 patients (54%). In a recent meta-analysis conducted by the investigators, the rate of seizure-free outcomes following epilepsy surgery was about 65%. Although this rate is higher than with the laser therapy, Dr. Widjaja pointed out that the laser intervention is less invasive and the hospital stay of a mean of 3.3 days is shorter than the week or so needed after surgery. This, she said, makes the procedure cost-effective.

Unlike surgery, laser therapy is also “particularly good” at reaching lesions deep in the brain without damaging surrounding tissue, Dr. Widjaja said.

Although the researchers have not evaluated seizure outcomes with respect to age, Dr. Widjaja believes age is not a major factor in outcomes. “I suspect it’s the type of lesion and how big the lesion is that mainly influences the outcome, rather than actual age,” she said.

Complications related to the laser therapy, including infections and bleeding, occurred in 15% of patients. Neurologic deficits affected about 8% of patients; however, these tended to be transient, Dr. Widjaja noted. There were two cases (1%) of permanent neurologic deficits, both of which involved weakness of arms or legs. This, said Dr. Widjaja, is less than the 5% rate of permanent neurologic deficits that occur following surgery, as reported in the literature.

There were no cases of major intracranial hemorrhage among the participants. At 30 days, there was one reported death.

Laser therapy is limited to relatively small lesions of no more than about 2 cm on average, Dr. Widjaja said. “We normally can’t treat huge lesions using laser therapy; they would need surgery.” However, it is possible to treat the same area twice. In the current study, 20 patients (11%) underwent laser therapy on one region on two occasions. Of these participants, 12 (60%) achieved freedom from seizures.

Dr. Widjaja noted that two additional epilepsy centers will soon be providing laser therapy and will expand the registry. In addition, the investigators are building a surgery registry that will enable them to compare outcomes of laser treatment with surgery.

Currently, laser therapy is available only at specialized epilepsy centers that perform surgery.
 

‘Very important’ research

Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, Boston, called this is “a very important study.”

Laser therapy “offers the opportunity for very rapid recovery from a minimally invasive, targeted technique while simultaneously offering promising outcomes,” said Dr. Goldenholz, who was not involved with the research.

He noted the importance of the investigators’ choosing freedom from seizures as the outcome of interest. In addition, the 54% seizure-freedom rate in the study is “substantially better” than rates from other interventions, he said.

“To put the results into perspective, other work has found that these same patients would have a less than 10% chance of seizure freedom if many different drug combinations were tried,” said Dr. Goldenholz.

He noted that the 1-year outcomes “are a good first time point” but that it is very important to assess longer-term outcomes. “Often, postsurgical outcomes are worse when looking at 2 or 5 years postoperatively,” he added. These longer-term data will be important “to fully inform our patients about long-term prognosis,” Dr. Goldenholz said.

Still, given the overall favorable results so far, “I think more centers will be likely to explore this newer technology,” he said.

The study was funded by the Pediatric Epilepsy Research Foundation. The study authors and Dr. Goldenholz report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

A new type of laser therapy is safe and effective for children with drug-resistant epilepsy, new research suggests. In a study of nearly 150 children, more than half of those who received MRI-guided laser interstitial thermal therapy (MRgLITT) were seizure free at 1 year.

Results show that this “is a new and promising therapy” for children for whom drug therapy has failed, said study investigator Elysa Widjaja, MD, a pediatric neuroradiologist at the Hospital for Sick Children and professor in the department of medical imaging, University of Toronto.

In addition, the procedure is less invasive and requires a shorter hospital stay than does open epilepsy surgery, Dr. Widjaja said.

The findings were presented at the annual meeting of the American Epilepsy Society, which was held online this year because of the COVID-19 pandemic.
 

Registry study

To date, most published studies on the laser procedure have had a small number of participants from only a few centers, Dr. Widjaja noted. “The aim of our registry is to collect data from multiple centers in both Canada and the U.S. to try to get a better understanding of the outcomes following laser therapy and the complications associated with this treatment,” she said.

In the procedure, a surgeon drills a tiny hole through the skull and, guided by MRI, inserts a very thin laser fiber into the center of the lesion. Heat then ablates the affected brain region.

From the dedicated registry, researchers recruited 182 children who were treated with MRgLITT at seven pediatric centers in the United States and two centers in Canada. The youngest patient was aged 14 months, and the oldest was aged 21 years (mean age, 11.2 years). Some pediatric hospitals treat patients up to age 21, Dr. Widjaja noted.

All of the study participants had focal epilepsy, “so the seizures are coming from a defined area of the brain,” she added. In addition, study participants’ conditions were drug-resistant, defined as conditions in which two antiseizure medications had previously failed.

The mean age at seizure onset was 5.4 years, and the mean number of antiepileptic drugs that were taken was 2.3.

Before receiving the therapy, children typically undergo extensive analyses, including MRI and video electroencephalography, to pinpoint where in the brain the seizures originate. Dr. Widjaja noted that the specific area of the brain that is affected varies widely from child to child.

The investigators collected baseline clinical characteristic and procedural data, including ablation site, type of lesion, length of stay, complications, number of MRgLITT procedures, and seizure outcome. To gather this information, they used a secure electronic platform designed to collect and store research data.
 

Seizure freedom

Among 137 patients for whom 1-year seizure outcomes were available, seizure freedom was reported for 74 patients (54%). In a recent meta-analysis conducted by the investigators, the rate of seizure-free outcomes following epilepsy surgery was about 65%. Although this rate is higher than with the laser therapy, Dr. Widjaja pointed out that the laser intervention is less invasive and the hospital stay of a mean of 3.3 days is shorter than the week or so needed after surgery. This, she said, makes the procedure cost-effective.

Unlike surgery, laser therapy is also “particularly good” at reaching lesions deep in the brain without damaging surrounding tissue, Dr. Widjaja said.

Although the researchers have not evaluated seizure outcomes with respect to age, Dr. Widjaja believes age is not a major factor in outcomes. “I suspect it’s the type of lesion and how big the lesion is that mainly influences the outcome, rather than actual age,” she said.

Complications related to the laser therapy, including infections and bleeding, occurred in 15% of patients. Neurologic deficits affected about 8% of patients; however, these tended to be transient, Dr. Widjaja noted. There were two cases (1%) of permanent neurologic deficits, both of which involved weakness of arms or legs. This, said Dr. Widjaja, is less than the 5% rate of permanent neurologic deficits that occur following surgery, as reported in the literature.

There were no cases of major intracranial hemorrhage among the participants. At 30 days, there was one reported death.

Laser therapy is limited to relatively small lesions of no more than about 2 cm on average, Dr. Widjaja said. “We normally can’t treat huge lesions using laser therapy; they would need surgery.” However, it is possible to treat the same area twice. In the current study, 20 patients (11%) underwent laser therapy on one region on two occasions. Of these participants, 12 (60%) achieved freedom from seizures.

Dr. Widjaja noted that two additional epilepsy centers will soon be providing laser therapy and will expand the registry. In addition, the investigators are building a surgery registry that will enable them to compare outcomes of laser treatment with surgery.

Currently, laser therapy is available only at specialized epilepsy centers that perform surgery.
 

‘Very important’ research

Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, Boston, called this is “a very important study.”

Laser therapy “offers the opportunity for very rapid recovery from a minimally invasive, targeted technique while simultaneously offering promising outcomes,” said Dr. Goldenholz, who was not involved with the research.

He noted the importance of the investigators’ choosing freedom from seizures as the outcome of interest. In addition, the 54% seizure-freedom rate in the study is “substantially better” than rates from other interventions, he said.

“To put the results into perspective, other work has found that these same patients would have a less than 10% chance of seizure freedom if many different drug combinations were tried,” said Dr. Goldenholz.

He noted that the 1-year outcomes “are a good first time point” but that it is very important to assess longer-term outcomes. “Often, postsurgical outcomes are worse when looking at 2 or 5 years postoperatively,” he added. These longer-term data will be important “to fully inform our patients about long-term prognosis,” Dr. Goldenholz said.

Still, given the overall favorable results so far, “I think more centers will be likely to explore this newer technology,” he said.

The study was funded by the Pediatric Epilepsy Research Foundation. The study authors and Dr. Goldenholz report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

A new type of laser therapy is safe and effective for children with drug-resistant epilepsy, new research suggests. In a study of nearly 150 children, more than half of those who received MRI-guided laser interstitial thermal therapy (MRgLITT) were seizure free at 1 year.

Results show that this “is a new and promising therapy” for children for whom drug therapy has failed, said study investigator Elysa Widjaja, MD, a pediatric neuroradiologist at the Hospital for Sick Children and professor in the department of medical imaging, University of Toronto.

In addition, the procedure is less invasive and requires a shorter hospital stay than does open epilepsy surgery, Dr. Widjaja said.

The findings were presented at the annual meeting of the American Epilepsy Society, which was held online this year because of the COVID-19 pandemic.
 

Registry study

To date, most published studies on the laser procedure have had a small number of participants from only a few centers, Dr. Widjaja noted. “The aim of our registry is to collect data from multiple centers in both Canada and the U.S. to try to get a better understanding of the outcomes following laser therapy and the complications associated with this treatment,” she said.

In the procedure, a surgeon drills a tiny hole through the skull and, guided by MRI, inserts a very thin laser fiber into the center of the lesion. Heat then ablates the affected brain region.

From the dedicated registry, researchers recruited 182 children who were treated with MRgLITT at seven pediatric centers in the United States and two centers in Canada. The youngest patient was aged 14 months, and the oldest was aged 21 years (mean age, 11.2 years). Some pediatric hospitals treat patients up to age 21, Dr. Widjaja noted.

All of the study participants had focal epilepsy, “so the seizures are coming from a defined area of the brain,” she added. In addition, study participants’ conditions were drug-resistant, defined as conditions in which two antiseizure medications had previously failed.

The mean age at seizure onset was 5.4 years, and the mean number of antiepileptic drugs that were taken was 2.3.

Before receiving the therapy, children typically undergo extensive analyses, including MRI and video electroencephalography, to pinpoint where in the brain the seizures originate. Dr. Widjaja noted that the specific area of the brain that is affected varies widely from child to child.

The investigators collected baseline clinical characteristic and procedural data, including ablation site, type of lesion, length of stay, complications, number of MRgLITT procedures, and seizure outcome. To gather this information, they used a secure electronic platform designed to collect and store research data.
 

Seizure freedom

Among 137 patients for whom 1-year seizure outcomes were available, seizure freedom was reported for 74 patients (54%). In a recent meta-analysis conducted by the investigators, the rate of seizure-free outcomes following epilepsy surgery was about 65%. Although this rate is higher than with the laser therapy, Dr. Widjaja pointed out that the laser intervention is less invasive and the hospital stay of a mean of 3.3 days is shorter than the week or so needed after surgery. This, she said, makes the procedure cost-effective.

Unlike surgery, laser therapy is also “particularly good” at reaching lesions deep in the brain without damaging surrounding tissue, Dr. Widjaja said.

Although the researchers have not evaluated seizure outcomes with respect to age, Dr. Widjaja believes age is not a major factor in outcomes. “I suspect it’s the type of lesion and how big the lesion is that mainly influences the outcome, rather than actual age,” she said.

Complications related to the laser therapy, including infections and bleeding, occurred in 15% of patients. Neurologic deficits affected about 8% of patients; however, these tended to be transient, Dr. Widjaja noted. There were two cases (1%) of permanent neurologic deficits, both of which involved weakness of arms or legs. This, said Dr. Widjaja, is less than the 5% rate of permanent neurologic deficits that occur following surgery, as reported in the literature.

There were no cases of major intracranial hemorrhage among the participants. At 30 days, there was one reported death.

Laser therapy is limited to relatively small lesions of no more than about 2 cm on average, Dr. Widjaja said. “We normally can’t treat huge lesions using laser therapy; they would need surgery.” However, it is possible to treat the same area twice. In the current study, 20 patients (11%) underwent laser therapy on one region on two occasions. Of these participants, 12 (60%) achieved freedom from seizures.

Dr. Widjaja noted that two additional epilepsy centers will soon be providing laser therapy and will expand the registry. In addition, the investigators are building a surgery registry that will enable them to compare outcomes of laser treatment with surgery.

Currently, laser therapy is available only at specialized epilepsy centers that perform surgery.
 

‘Very important’ research

Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, Boston, called this is “a very important study.”

Laser therapy “offers the opportunity for very rapid recovery from a minimally invasive, targeted technique while simultaneously offering promising outcomes,” said Dr. Goldenholz, who was not involved with the research.

He noted the importance of the investigators’ choosing freedom from seizures as the outcome of interest. In addition, the 54% seizure-freedom rate in the study is “substantially better” than rates from other interventions, he said.

“To put the results into perspective, other work has found that these same patients would have a less than 10% chance of seizure freedom if many different drug combinations were tried,” said Dr. Goldenholz.

He noted that the 1-year outcomes “are a good first time point” but that it is very important to assess longer-term outcomes. “Often, postsurgical outcomes are worse when looking at 2 or 5 years postoperatively,” he added. These longer-term data will be important “to fully inform our patients about long-term prognosis,” Dr. Goldenholz said.

Still, given the overall favorable results so far, “I think more centers will be likely to explore this newer technology,” he said.

The study was funded by the Pediatric Epilepsy Research Foundation. The study authors and Dr. Goldenholz report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Sudden unexpected death in epilepsy (SUDEP) may explain 3% of all sudden deaths in children – a prevalence rate that is at least three times greater than previously reported estimates – new research shows.

Just a few years ago, the message regarding SUDEP was that “it’s very rare in children so you don’t need to worry about it,” said study investigator Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke.

These new study results should refocus the message that “the condition is rare, but not as rare as we thought it was,” she said.

The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

Population-based study

Most of the research examining the pediatric SUDEP rate in the United States is based on convenience samples, with few population-based studies.

The investigators used data from the National Institutes of Health/Centers for Disease Control and Prevention Sudden Death in the Young Case Registry. The CDC set up the registry several years ago to record cases of sudden infant death syndrome and sudden deaths in children resulting from violence, trauma, and abuse. Its mandate has since expanded, and the registry now includes data on sudden cardiac death and SUDEP in children.

The current study included children with SUDEP or cardiac/SUDEP who were aged 0-17 years from several states or jurisdictions from 2015 to 2017. Cases were deemed to be SUDEP if the patient had a history of epilepsy, with or without evidence of seizure at the time of death, but excluding status epilepticus.

Criteria for cardiac/SUDEP cases included having a family history of a heritable cardiac condition or sudden death before age 50 years, a personal history of cardiac disease, or a clinical history suggestive of a cardiac disorder, such as death during exertion.

This second category, said Dr. Whittemore, might capture children with Dravet syndrome, a type of epilepsy caused by a genetic mutation that affects both the heart and the brain. “In these cases, it’s sometimes difficult to tell if the child died due to a heart complication or due to epilepsy,” she said.

The analysis included 1,776 cases. Of these, 3% were categorized as SUDEP, and 1% were categorized as cardiac/SUDEP.

The relatively high prevalence of SUDEP was somewhat unexpected, inasmuch as previous reports estimated the rate to be 0.5%-1%, said Dr. Whittemore.

She noted that the current study is population based and included all cases of child death, whereas past reports relied on death certificates. “That probably missed a lot of deaths because they weren’t recorded accurately on the death certificate or weren’t reported in a way that anyone could ascertain that it was a death in someone that had epilepsy.”
 

Racial differences

Autopsy rates were lower for SUDEP (70%), compared with other categories of death in the registry (81%-100%).

In most jurisdictions, parents must give consent for an autopsy to be performed for a child, and many parents who have suffered such a sudden loss don’t want further investigation, said Dr. Whittemore. “If you know your child had epilepsy, doing an autopsy really isn’t going to tell you very much. You already know they had epilepsy; you may not know the cause of the epilepsy, but an autopsy isn’t going to reveal as much as it would in children with sudden cardiac death.”

SUDEP was equally common in boys and girls. However, the SUDEP mortality rate was higher in Black children (0.32/100,000) than in White children (0.22/100,000). It’s unclear from this study why this is so, but another study that examined SUDEP rates by ZIP code suggested that the higher rate may be caused by socioeconomic factors, said Dr. Whittemore. “Black children from a lower-income family who don’t have access to care may not be getting as good treatment and so have more uncontrolled seizures, which may lead to higher incidence of SUDEP.”

SUDEP occurred at all ages, but mortality rates were highest among patients aged 0-1 year (0.53/100,000) and in those aged 14-17 years (0.31/100,000). Dr. Whittemore speculated that SUDEP rates were higher among the youngest patients because their seizures have just started, and it may be more difficult to bring them under control. In the past, some of these cases may have been classified as sudden infant death syndrome but are now recognized as SUDEP.

As for the older group, research shows that puberty can result in poorer seizure control, which may put teens at elevated risk for SUDEP, said Dr. Whittemore. She added that, as teens continue to age, SUDEP risk may continue to increase. Dr. Whittemore suggested that young adults who head off to college may stop taking their antiseizure medications or consume alcohol while taking these drugs.
 

Failure of arousal

The study results revealed that most SUDEP cases occurred during sleep without a witness. Dr. Whittemore believes that sleeping with one’s face in a pillow may prevent the reflex required to turn the head to breathe. “It’s sort of a failure of arousal that is potentially the underlying mechanism.”

In some cases, there are signs children had a seizure just prior to death, said Dr. Whittemore.

The researchers have now collected information for 2018 and 2019 and plan to add these data to the current 3-year results. “We will now expand our analysis to include these new numbers to make sure the trends we saw in those 3 years are continuing,” said Dr. Whittemore. The new results should help raise awareness that SUDEP is not as rare as previously believed.

Parents of children with epilepsy can take steps to help reduce the risk for SUDEP, she added. For example, they can use night monitors, and for the children at highest risk (e.g., those with Dravet syndrome), they can use an “alarm blanket” that alerts them when the child moves.
 

Much is still unknown

Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, New York, who has participated in SUDEP research, said it “raises important questions about SUDEP in children and about racial disparities in SUDEP.”

The understanding of SUDEP so far “leaves much to be desired,” said Dr. Goldenholz. “We don’t yet know why it happens, and we don’t yet know how to prevent it.” The current study “brings a couple of new data points to the table which need further validation, confirmation, and explanation.”

The Sudden Death in Young Case Registry is supported by the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke; and the CDC. The investigators and Dr. Goldenholz disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Sudden unexpected death in epilepsy (SUDEP) may explain 3% of all sudden deaths in children – a prevalence rate that is at least three times greater than previously reported estimates – new research shows.

Just a few years ago, the message regarding SUDEP was that “it’s very rare in children so you don’t need to worry about it,” said study investigator Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke.

These new study results should refocus the message that “the condition is rare, but not as rare as we thought it was,” she said.

The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

Population-based study

Most of the research examining the pediatric SUDEP rate in the United States is based on convenience samples, with few population-based studies.

The investigators used data from the National Institutes of Health/Centers for Disease Control and Prevention Sudden Death in the Young Case Registry. The CDC set up the registry several years ago to record cases of sudden infant death syndrome and sudden deaths in children resulting from violence, trauma, and abuse. Its mandate has since expanded, and the registry now includes data on sudden cardiac death and SUDEP in children.

The current study included children with SUDEP or cardiac/SUDEP who were aged 0-17 years from several states or jurisdictions from 2015 to 2017. Cases were deemed to be SUDEP if the patient had a history of epilepsy, with or without evidence of seizure at the time of death, but excluding status epilepticus.

Criteria for cardiac/SUDEP cases included having a family history of a heritable cardiac condition or sudden death before age 50 years, a personal history of cardiac disease, or a clinical history suggestive of a cardiac disorder, such as death during exertion.

This second category, said Dr. Whittemore, might capture children with Dravet syndrome, a type of epilepsy caused by a genetic mutation that affects both the heart and the brain. “In these cases, it’s sometimes difficult to tell if the child died due to a heart complication or due to epilepsy,” she said.

The analysis included 1,776 cases. Of these, 3% were categorized as SUDEP, and 1% were categorized as cardiac/SUDEP.

The relatively high prevalence of SUDEP was somewhat unexpected, inasmuch as previous reports estimated the rate to be 0.5%-1%, said Dr. Whittemore.

She noted that the current study is population based and included all cases of child death, whereas past reports relied on death certificates. “That probably missed a lot of deaths because they weren’t recorded accurately on the death certificate or weren’t reported in a way that anyone could ascertain that it was a death in someone that had epilepsy.”
 

Racial differences

Autopsy rates were lower for SUDEP (70%), compared with other categories of death in the registry (81%-100%).

In most jurisdictions, parents must give consent for an autopsy to be performed for a child, and many parents who have suffered such a sudden loss don’t want further investigation, said Dr. Whittemore. “If you know your child had epilepsy, doing an autopsy really isn’t going to tell you very much. You already know they had epilepsy; you may not know the cause of the epilepsy, but an autopsy isn’t going to reveal as much as it would in children with sudden cardiac death.”

SUDEP was equally common in boys and girls. However, the SUDEP mortality rate was higher in Black children (0.32/100,000) than in White children (0.22/100,000). It’s unclear from this study why this is so, but another study that examined SUDEP rates by ZIP code suggested that the higher rate may be caused by socioeconomic factors, said Dr. Whittemore. “Black children from a lower-income family who don’t have access to care may not be getting as good treatment and so have more uncontrolled seizures, which may lead to higher incidence of SUDEP.”

SUDEP occurred at all ages, but mortality rates were highest among patients aged 0-1 year (0.53/100,000) and in those aged 14-17 years (0.31/100,000). Dr. Whittemore speculated that SUDEP rates were higher among the youngest patients because their seizures have just started, and it may be more difficult to bring them under control. In the past, some of these cases may have been classified as sudden infant death syndrome but are now recognized as SUDEP.

As for the older group, research shows that puberty can result in poorer seizure control, which may put teens at elevated risk for SUDEP, said Dr. Whittemore. She added that, as teens continue to age, SUDEP risk may continue to increase. Dr. Whittemore suggested that young adults who head off to college may stop taking their antiseizure medications or consume alcohol while taking these drugs.
 

Failure of arousal

The study results revealed that most SUDEP cases occurred during sleep without a witness. Dr. Whittemore believes that sleeping with one’s face in a pillow may prevent the reflex required to turn the head to breathe. “It’s sort of a failure of arousal that is potentially the underlying mechanism.”

In some cases, there are signs children had a seizure just prior to death, said Dr. Whittemore.

The researchers have now collected information for 2018 and 2019 and plan to add these data to the current 3-year results. “We will now expand our analysis to include these new numbers to make sure the trends we saw in those 3 years are continuing,” said Dr. Whittemore. The new results should help raise awareness that SUDEP is not as rare as previously believed.

Parents of children with epilepsy can take steps to help reduce the risk for SUDEP, she added. For example, they can use night monitors, and for the children at highest risk (e.g., those with Dravet syndrome), they can use an “alarm blanket” that alerts them when the child moves.
 

Much is still unknown

Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, New York, who has participated in SUDEP research, said it “raises important questions about SUDEP in children and about racial disparities in SUDEP.”

The understanding of SUDEP so far “leaves much to be desired,” said Dr. Goldenholz. “We don’t yet know why it happens, and we don’t yet know how to prevent it.” The current study “brings a couple of new data points to the table which need further validation, confirmation, and explanation.”

The Sudden Death in Young Case Registry is supported by the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke; and the CDC. The investigators and Dr. Goldenholz disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Sudden unexpected death in epilepsy (SUDEP) may explain 3% of all sudden deaths in children – a prevalence rate that is at least three times greater than previously reported estimates – new research shows.

Just a few years ago, the message regarding SUDEP was that “it’s very rare in children so you don’t need to worry about it,” said study investigator Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke.

These new study results should refocus the message that “the condition is rare, but not as rare as we thought it was,” she said.

The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

Population-based study

Most of the research examining the pediatric SUDEP rate in the United States is based on convenience samples, with few population-based studies.

The investigators used data from the National Institutes of Health/Centers for Disease Control and Prevention Sudden Death in the Young Case Registry. The CDC set up the registry several years ago to record cases of sudden infant death syndrome and sudden deaths in children resulting from violence, trauma, and abuse. Its mandate has since expanded, and the registry now includes data on sudden cardiac death and SUDEP in children.

The current study included children with SUDEP or cardiac/SUDEP who were aged 0-17 years from several states or jurisdictions from 2015 to 2017. Cases were deemed to be SUDEP if the patient had a history of epilepsy, with or without evidence of seizure at the time of death, but excluding status epilepticus.

Criteria for cardiac/SUDEP cases included having a family history of a heritable cardiac condition or sudden death before age 50 years, a personal history of cardiac disease, or a clinical history suggestive of a cardiac disorder, such as death during exertion.

This second category, said Dr. Whittemore, might capture children with Dravet syndrome, a type of epilepsy caused by a genetic mutation that affects both the heart and the brain. “In these cases, it’s sometimes difficult to tell if the child died due to a heart complication or due to epilepsy,” she said.

The analysis included 1,776 cases. Of these, 3% were categorized as SUDEP, and 1% were categorized as cardiac/SUDEP.

The relatively high prevalence of SUDEP was somewhat unexpected, inasmuch as previous reports estimated the rate to be 0.5%-1%, said Dr. Whittemore.

She noted that the current study is population based and included all cases of child death, whereas past reports relied on death certificates. “That probably missed a lot of deaths because they weren’t recorded accurately on the death certificate or weren’t reported in a way that anyone could ascertain that it was a death in someone that had epilepsy.”
 

Racial differences

Autopsy rates were lower for SUDEP (70%), compared with other categories of death in the registry (81%-100%).

In most jurisdictions, parents must give consent for an autopsy to be performed for a child, and many parents who have suffered such a sudden loss don’t want further investigation, said Dr. Whittemore. “If you know your child had epilepsy, doing an autopsy really isn’t going to tell you very much. You already know they had epilepsy; you may not know the cause of the epilepsy, but an autopsy isn’t going to reveal as much as it would in children with sudden cardiac death.”

SUDEP was equally common in boys and girls. However, the SUDEP mortality rate was higher in Black children (0.32/100,000) than in White children (0.22/100,000). It’s unclear from this study why this is so, but another study that examined SUDEP rates by ZIP code suggested that the higher rate may be caused by socioeconomic factors, said Dr. Whittemore. “Black children from a lower-income family who don’t have access to care may not be getting as good treatment and so have more uncontrolled seizures, which may lead to higher incidence of SUDEP.”

SUDEP occurred at all ages, but mortality rates were highest among patients aged 0-1 year (0.53/100,000) and in those aged 14-17 years (0.31/100,000). Dr. Whittemore speculated that SUDEP rates were higher among the youngest patients because their seizures have just started, and it may be more difficult to bring them under control. In the past, some of these cases may have been classified as sudden infant death syndrome but are now recognized as SUDEP.

As for the older group, research shows that puberty can result in poorer seizure control, which may put teens at elevated risk for SUDEP, said Dr. Whittemore. She added that, as teens continue to age, SUDEP risk may continue to increase. Dr. Whittemore suggested that young adults who head off to college may stop taking their antiseizure medications or consume alcohol while taking these drugs.
 

Failure of arousal

The study results revealed that most SUDEP cases occurred during sleep without a witness. Dr. Whittemore believes that sleeping with one’s face in a pillow may prevent the reflex required to turn the head to breathe. “It’s sort of a failure of arousal that is potentially the underlying mechanism.”

In some cases, there are signs children had a seizure just prior to death, said Dr. Whittemore.

The researchers have now collected information for 2018 and 2019 and plan to add these data to the current 3-year results. “We will now expand our analysis to include these new numbers to make sure the trends we saw in those 3 years are continuing,” said Dr. Whittemore. The new results should help raise awareness that SUDEP is not as rare as previously believed.

Parents of children with epilepsy can take steps to help reduce the risk for SUDEP, she added. For example, they can use night monitors, and for the children at highest risk (e.g., those with Dravet syndrome), they can use an “alarm blanket” that alerts them when the child moves.
 

Much is still unknown

Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, New York, who has participated in SUDEP research, said it “raises important questions about SUDEP in children and about racial disparities in SUDEP.”

The understanding of SUDEP so far “leaves much to be desired,” said Dr. Goldenholz. “We don’t yet know why it happens, and we don’t yet know how to prevent it.” The current study “brings a couple of new data points to the table which need further validation, confirmation, and explanation.”

The Sudden Death in Young Case Registry is supported by the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke; and the CDC. The investigators and Dr. Goldenholz disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Children with epilepsy with no previous psychiatric diagnosis have alarmingly high rates of suicidal thoughts and behaviors, new research suggests. In a study of more than 100 youth with the disorder, more than 40% had depression, 30% had anxiety, and about 1 in 10 exhibited signs of suicidal thoughts and behaviors.

These rates “are really worrisome” and highlight the need to screen all children and young adults with epilepsy for psychiatric disorders, said study author Tatiana Falcone, MD, assistant professor of neurology and child and adolescent psychiatry at the Cleveland Clinic.

“It’s very important to screen for suicidality and for depression and anxiety, even when patients aren’t reporting symptoms,” said Dr. Falcone.

Previous research shows children with epilepsy will attend the emergency room with symptoms such as headache or stomachache “when the main reason for the visit was the kid was suicidal,” Dr. Falcone said. “Unless you ask the specific question: ‘Are you having thoughts about hurting yourself?’ this will go unreported,” she added.

The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

Red flag

Not much is known about suicidality in children and youth with epilepsy except that depression and anxiety – the most common psychiatric comorbidities in this population – appear to contribute to suicidal thoughts.

Dr. Falcone said that she and her colleagues often see children and adolescents with epilepsy in their clinic who have attempted suicide. In recent years, the clinicians have increased efforts to try to identify them before they carry out a successful suicide attempt, said lead investigator Anjali Dagar, MD, clinical research psychiatry fellow at Cleveland Clinic.

The study included 119 patients aged 10-24 years (mean age, 15.8 years; 54.6% female). All attended an epilepsy clinic or underwent testing in the pediatric epilepsy monitoring unit at the Cleveland Clinic and did not have a psychiatric diagnosis.

Epilepsy severity ranged among study participants. About half were drug resistant and were at the center for surgical evaluation and the others were newly diagnosed.

Participants filled out questionnaires to self-report psychiatric conditions. The validated screening tools included the Center for Epidemiological Studies Depression Scale for Children (CES-DC), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Ask Suicide–Screening Questions (ASQ).

A score of 15 or higher on the CES-DC indicates a risk for depression. On the SCARED test, a score higher than 32 indicates anxiety. Recent research has shown that anxiety is a main risk factor “in moving people from contemplating suicide to actually carrying it out,” Dr. Falcone said.

The ASQ includes four questions about suicidal thoughts and whether respondents have tried to hurt themselves. Dr. Dagar noted that a positive response to any of these questions should raise a red flag.
 

Very high rates

Results showed that almost one-third (30.2%) of the participants scored positive for anxiety on SCARED and 41.2% scored positive for depression on the CSE-DC. These are “very high” rates, Dr. Falcone said. For comparison, the rate of reported anxiety is less than 10% in school surveys.

In addition, the Centers for Disease Control and Prevention reports about 3% of 2- to 17-year-olds in the general population have depression. Even compared with other chronic illnesses (including diabetes, heart disease, and cancer), children with epilepsy have a higher rate of depression, said Dr. Falcone.

More than 1 in 10 (10.9%) participants in the study exhibited signs of suicidality, as shown by having at least one positive response on the ASQ. “That’s a lot,” and much higher than the estimated rate in the general teen population, Dr. Falcone noted.

She noted that “these are just general kids with epilepsy” who had not been previously diagnosed with a psychiatric disorder.

“Depression, anxiety, and suicidality are very frequent comorbidities in patients with epilepsy; and even if a patient is not reporting any symptoms, we should be asking these questions to help them,” she said.

Study participants who had at least one positive response on the ASQ had a mean score of 32.1 on the SCARED, compared with a mean score of 18.3 for those who did not have a positive response on the ASQ (P = .003).

“We wanted to see if there was a direct association in our sample between anxiety and suicidal thoughts, and we found [that] yes there was,” Dr. Falcone said. There was also an association with depression. More than 26% of participants who scored 16 or higher on the CES-DC indicated at least one positive response on the ASQ. This is significantly higher than those who scored 15 or below on the CES-DC (P < .0001).
 

Bidirectional relationship

The findings suggest that either depression or anxiety may contribute to suicidal thoughts or behaviors, Dr. Dagar said. “It’s like two hands. It could be anxiety leading to suicidality, or it could be depression, or it could be both.”

Dr. Falcone noted that children with epilepsy who aren’t sure when they’ll get their next seizure, or who are bullied at school for being different, may be especially prone to anxiety or depression.

There’s a bit of a “chicken-and-egg” relationship between depression and epilepsy, a disorder affecting electrical signals in the brain, she said. Previous research has shown that a “bidirectional relationship” is involved.

“Even in patients with depression who are not diagnosed with epilepsy, the incidence of epilepsy is 3% higher just because you have depression,” Dr. Falcone said.

Suicidal youth tend to attempt suicide more than once. Dr. Falcone and colleagues are trying to intervene “at different levels,” be that in the hospital or as an outpatient, to prevent this from happening. “We want to find out what different things we can do to engage them and improve the probability they don’t reattempt,” she said.

All children and youth with epilepsy should be screened for anxiety, depression, and suicidal thoughts and behaviors. From age 10 years, children with epilepsy should be screened at least once a year, but those with a psychiatric disorder should be screened more often, Dr. Falcone added. The investigators note their findings need to be confirmed in larger, more diverse studies.
 

Importance of screening

Michael Privitera, MD, director of the Epilepsy Center and professor of neurology at the University of Cincinnati Gardner Neuroscience Institute, said the findings reinforce that, as with adults, depression and anxiety are common in children with epilepsy.

“Neurologists should take advantage of the many psychiatric screening tools available to identify these problems in their pediatric and adult patients,” Dr. Privitera said. Even more importantly, screening may help identify those who may be at highest risk of suicide.

The study was funded by the Health Resources Services Administration. The investigators and Dr. Privitera have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Children with epilepsy with no previous psychiatric diagnosis have alarmingly high rates of suicidal thoughts and behaviors, new research suggests. In a study of more than 100 youth with the disorder, more than 40% had depression, 30% had anxiety, and about 1 in 10 exhibited signs of suicidal thoughts and behaviors.

These rates “are really worrisome” and highlight the need to screen all children and young adults with epilepsy for psychiatric disorders, said study author Tatiana Falcone, MD, assistant professor of neurology and child and adolescent psychiatry at the Cleveland Clinic.

“It’s very important to screen for suicidality and for depression and anxiety, even when patients aren’t reporting symptoms,” said Dr. Falcone.

Previous research shows children with epilepsy will attend the emergency room with symptoms such as headache or stomachache “when the main reason for the visit was the kid was suicidal,” Dr. Falcone said. “Unless you ask the specific question: ‘Are you having thoughts about hurting yourself?’ this will go unreported,” she added.

The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

Red flag

Not much is known about suicidality in children and youth with epilepsy except that depression and anxiety – the most common psychiatric comorbidities in this population – appear to contribute to suicidal thoughts.

Dr. Falcone said that she and her colleagues often see children and adolescents with epilepsy in their clinic who have attempted suicide. In recent years, the clinicians have increased efforts to try to identify them before they carry out a successful suicide attempt, said lead investigator Anjali Dagar, MD, clinical research psychiatry fellow at Cleveland Clinic.

The study included 119 patients aged 10-24 years (mean age, 15.8 years; 54.6% female). All attended an epilepsy clinic or underwent testing in the pediatric epilepsy monitoring unit at the Cleveland Clinic and did not have a psychiatric diagnosis.

Epilepsy severity ranged among study participants. About half were drug resistant and were at the center for surgical evaluation and the others were newly diagnosed.

Participants filled out questionnaires to self-report psychiatric conditions. The validated screening tools included the Center for Epidemiological Studies Depression Scale for Children (CES-DC), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Ask Suicide–Screening Questions (ASQ).

A score of 15 or higher on the CES-DC indicates a risk for depression. On the SCARED test, a score higher than 32 indicates anxiety. Recent research has shown that anxiety is a main risk factor “in moving people from contemplating suicide to actually carrying it out,” Dr. Falcone said.

The ASQ includes four questions about suicidal thoughts and whether respondents have tried to hurt themselves. Dr. Dagar noted that a positive response to any of these questions should raise a red flag.
 

Very high rates

Results showed that almost one-third (30.2%) of the participants scored positive for anxiety on SCARED and 41.2% scored positive for depression on the CSE-DC. These are “very high” rates, Dr. Falcone said. For comparison, the rate of reported anxiety is less than 10% in school surveys.

In addition, the Centers for Disease Control and Prevention reports about 3% of 2- to 17-year-olds in the general population have depression. Even compared with other chronic illnesses (including diabetes, heart disease, and cancer), children with epilepsy have a higher rate of depression, said Dr. Falcone.

More than 1 in 10 (10.9%) participants in the study exhibited signs of suicidality, as shown by having at least one positive response on the ASQ. “That’s a lot,” and much higher than the estimated rate in the general teen population, Dr. Falcone noted.

She noted that “these are just general kids with epilepsy” who had not been previously diagnosed with a psychiatric disorder.

“Depression, anxiety, and suicidality are very frequent comorbidities in patients with epilepsy; and even if a patient is not reporting any symptoms, we should be asking these questions to help them,” she said.

Study participants who had at least one positive response on the ASQ had a mean score of 32.1 on the SCARED, compared with a mean score of 18.3 for those who did not have a positive response on the ASQ (P = .003).

“We wanted to see if there was a direct association in our sample between anxiety and suicidal thoughts, and we found [that] yes there was,” Dr. Falcone said. There was also an association with depression. More than 26% of participants who scored 16 or higher on the CES-DC indicated at least one positive response on the ASQ. This is significantly higher than those who scored 15 or below on the CES-DC (P < .0001).
 

Bidirectional relationship

The findings suggest that either depression or anxiety may contribute to suicidal thoughts or behaviors, Dr. Dagar said. “It’s like two hands. It could be anxiety leading to suicidality, or it could be depression, or it could be both.”

Dr. Falcone noted that children with epilepsy who aren’t sure when they’ll get their next seizure, or who are bullied at school for being different, may be especially prone to anxiety or depression.

There’s a bit of a “chicken-and-egg” relationship between depression and epilepsy, a disorder affecting electrical signals in the brain, she said. Previous research has shown that a “bidirectional relationship” is involved.

“Even in patients with depression who are not diagnosed with epilepsy, the incidence of epilepsy is 3% higher just because you have depression,” Dr. Falcone said.

Suicidal youth tend to attempt suicide more than once. Dr. Falcone and colleagues are trying to intervene “at different levels,” be that in the hospital or as an outpatient, to prevent this from happening. “We want to find out what different things we can do to engage them and improve the probability they don’t reattempt,” she said.

All children and youth with epilepsy should be screened for anxiety, depression, and suicidal thoughts and behaviors. From age 10 years, children with epilepsy should be screened at least once a year, but those with a psychiatric disorder should be screened more often, Dr. Falcone added. The investigators note their findings need to be confirmed in larger, more diverse studies.
 

Importance of screening

Michael Privitera, MD, director of the Epilepsy Center and professor of neurology at the University of Cincinnati Gardner Neuroscience Institute, said the findings reinforce that, as with adults, depression and anxiety are common in children with epilepsy.

“Neurologists should take advantage of the many psychiatric screening tools available to identify these problems in their pediatric and adult patients,” Dr. Privitera said. Even more importantly, screening may help identify those who may be at highest risk of suicide.

The study was funded by the Health Resources Services Administration. The investigators and Dr. Privitera have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Children with epilepsy with no previous psychiatric diagnosis have alarmingly high rates of suicidal thoughts and behaviors, new research suggests. In a study of more than 100 youth with the disorder, more than 40% had depression, 30% had anxiety, and about 1 in 10 exhibited signs of suicidal thoughts and behaviors.

These rates “are really worrisome” and highlight the need to screen all children and young adults with epilepsy for psychiatric disorders, said study author Tatiana Falcone, MD, assistant professor of neurology and child and adolescent psychiatry at the Cleveland Clinic.

“It’s very important to screen for suicidality and for depression and anxiety, even when patients aren’t reporting symptoms,” said Dr. Falcone.

Previous research shows children with epilepsy will attend the emergency room with symptoms such as headache or stomachache “when the main reason for the visit was the kid was suicidal,” Dr. Falcone said. “Unless you ask the specific question: ‘Are you having thoughts about hurting yourself?’ this will go unreported,” she added.

The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

Red flag

Not much is known about suicidality in children and youth with epilepsy except that depression and anxiety – the most common psychiatric comorbidities in this population – appear to contribute to suicidal thoughts.

Dr. Falcone said that she and her colleagues often see children and adolescents with epilepsy in their clinic who have attempted suicide. In recent years, the clinicians have increased efforts to try to identify them before they carry out a successful suicide attempt, said lead investigator Anjali Dagar, MD, clinical research psychiatry fellow at Cleveland Clinic.

The study included 119 patients aged 10-24 years (mean age, 15.8 years; 54.6% female). All attended an epilepsy clinic or underwent testing in the pediatric epilepsy monitoring unit at the Cleveland Clinic and did not have a psychiatric diagnosis.

Epilepsy severity ranged among study participants. About half were drug resistant and were at the center for surgical evaluation and the others were newly diagnosed.

Participants filled out questionnaires to self-report psychiatric conditions. The validated screening tools included the Center for Epidemiological Studies Depression Scale for Children (CES-DC), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Ask Suicide–Screening Questions (ASQ).

A score of 15 or higher on the CES-DC indicates a risk for depression. On the SCARED test, a score higher than 32 indicates anxiety. Recent research has shown that anxiety is a main risk factor “in moving people from contemplating suicide to actually carrying it out,” Dr. Falcone said.

The ASQ includes four questions about suicidal thoughts and whether respondents have tried to hurt themselves. Dr. Dagar noted that a positive response to any of these questions should raise a red flag.
 

Very high rates

Results showed that almost one-third (30.2%) of the participants scored positive for anxiety on SCARED and 41.2% scored positive for depression on the CSE-DC. These are “very high” rates, Dr. Falcone said. For comparison, the rate of reported anxiety is less than 10% in school surveys.

In addition, the Centers for Disease Control and Prevention reports about 3% of 2- to 17-year-olds in the general population have depression. Even compared with other chronic illnesses (including diabetes, heart disease, and cancer), children with epilepsy have a higher rate of depression, said Dr. Falcone.

More than 1 in 10 (10.9%) participants in the study exhibited signs of suicidality, as shown by having at least one positive response on the ASQ. “That’s a lot,” and much higher than the estimated rate in the general teen population, Dr. Falcone noted.

She noted that “these are just general kids with epilepsy” who had not been previously diagnosed with a psychiatric disorder.

“Depression, anxiety, and suicidality are very frequent comorbidities in patients with epilepsy; and even if a patient is not reporting any symptoms, we should be asking these questions to help them,” she said.

Study participants who had at least one positive response on the ASQ had a mean score of 32.1 on the SCARED, compared with a mean score of 18.3 for those who did not have a positive response on the ASQ (P = .003).

“We wanted to see if there was a direct association in our sample between anxiety and suicidal thoughts, and we found [that] yes there was,” Dr. Falcone said. There was also an association with depression. More than 26% of participants who scored 16 or higher on the CES-DC indicated at least one positive response on the ASQ. This is significantly higher than those who scored 15 or below on the CES-DC (P < .0001).
 

Bidirectional relationship

The findings suggest that either depression or anxiety may contribute to suicidal thoughts or behaviors, Dr. Dagar said. “It’s like two hands. It could be anxiety leading to suicidality, or it could be depression, or it could be both.”

Dr. Falcone noted that children with epilepsy who aren’t sure when they’ll get their next seizure, or who are bullied at school for being different, may be especially prone to anxiety or depression.

There’s a bit of a “chicken-and-egg” relationship between depression and epilepsy, a disorder affecting electrical signals in the brain, she said. Previous research has shown that a “bidirectional relationship” is involved.

“Even in patients with depression who are not diagnosed with epilepsy, the incidence of epilepsy is 3% higher just because you have depression,” Dr. Falcone said.

Suicidal youth tend to attempt suicide more than once. Dr. Falcone and colleagues are trying to intervene “at different levels,” be that in the hospital or as an outpatient, to prevent this from happening. “We want to find out what different things we can do to engage them and improve the probability they don’t reattempt,” she said.

All children and youth with epilepsy should be screened for anxiety, depression, and suicidal thoughts and behaviors. From age 10 years, children with epilepsy should be screened at least once a year, but those with a psychiatric disorder should be screened more often, Dr. Falcone added. The investigators note their findings need to be confirmed in larger, more diverse studies.
 

Importance of screening

Michael Privitera, MD, director of the Epilepsy Center and professor of neurology at the University of Cincinnati Gardner Neuroscience Institute, said the findings reinforce that, as with adults, depression and anxiety are common in children with epilepsy.

“Neurologists should take advantage of the many psychiatric screening tools available to identify these problems in their pediatric and adult patients,” Dr. Privitera said. Even more importantly, screening may help identify those who may be at highest risk of suicide.

The study was funded by the Health Resources Services Administration. The investigators and Dr. Privitera have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.