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Short Takes
Pediatric Neurology 56 (2016) 1e2
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Commentary
Short Takes Steven G. Pavlakis MD * Center for Brain and Behavior, Maimonides Medical Center, The Brooklyn Hospital Center and Icahn School of Medicine at Mount Sinai, Brooklyn, New York
Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy: an open label, dose finding, and feasibility phase1/2 trial. Lancet Neurology 14:469477, 2015
A global perspective on hypertension: a Lancet Commission. Lancet 386:637-638, 2015
Pressler RM, Boylan GB, Marlow N, et al.
Flash Summary: In this comment the authors opine that hypertension is the number one killer through cerebrovascular disease (including stroke), affecting 1 billion individuals globally. Since awareness and treatment are very low in poor and middle-income countries, The Lancet has taken the initiative to launch a commission on hypertension whose aim is to generate a campaign to implement actions to improve management of hypertension globally.
Flash Summary: The authors report the result of a dose-finding, feasibility trial studying bumetanide (a loop diuretic) in newborns with seizures after hypoxic ischemic encephalopathy. Patients who did not respond to phenobarbital were given, in addition, bumetanide. The trial was terminated early because of possible side effects. The numbers were small (n ¼ 14) and toxicity could not be proved, but there was a suggestion of ototoxicity. In addition there was treatment failure. Bottom Line: It is important that more seizure trials are performed in the newborn. Phenobarbital and phenytoin are the medications historically used with topiramate and levetiracetam gaining recent proponents. Further studies are necessary, and this study design can work with some tweaking. For example, efficacy may need to be assessed over longer time periods. The study aimed for an 80% seizure reduction in newborns on electroencephalography, but five of the newborns had no seizures before initiation of medication and as such were a failure of treatment. A phase 1 and 2 trial is not designed for efficacy, so a failure of treatment is not proved. Phase 1 and 2 are typically designed to examine only dosage and safety. There are many roadblocks to newborn trials including entrenched dogmas. In addition, there is a movement for many neonatology divisions to become independent departments and cost centers separate from pediatric departments. Therefore more political roadblocks are appearing. Nevertheless, this study is a model, after some improvements, for what can be done for our newborn patients with epilepsy. We need to actively work with neonatologists.
Editor’s note: Short Takes offers a brief analysis by Steven G. Pavlakis of selected articles that may be of interest to child neurologists. Papers that strike the fancy of the analyst or the editors are selected for inclusion, but we welcome suggestions.
* Communications should be addressed to: Dr. Pavlakis; Center for Brain and Behavior; Maimonides Medical Center; The Brooklyn Hospital Center; 121 DeKalb Avenue; Brooklyn, NY 11201. E-mail address: [email protected] 0887-8994/$ e see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2015.10.003
Olsen MH, Spencer S.
Bottom Line: Here there is no pediatric component to this Commission. There is emerging evidence that adolescent hypertension affects cerebrovascular autoregulation, cognitive function including executive function, and even white matter tracks in young adults. There is also emerging evidence that hypertension may even play a role as a risk factor in some pediatric stroke. Since there is little awareness of hypertension in the adolescent in regard to early cerebrovascular disease, I believe that it is our role to disseminate the risk of adolescent hypertension to both poor and rich countries. This is an underrecognized public health problem that deserves our attention as pediatric neurologists.
2
Short Takes / Pediatric Neurology 56 (2016) 1e2
Prenatal factors in singletons with cerebral palsy born at or near term. N Engl J Med 373:946-953, 2015 Nelson KB, Blair E. Flash Summary: Cerebral palsy has a prevalence of about 2 in 1000 children who were born at term. The prevalence has not changed over the past three decades. Here, in a review, Nelson and Blair show that most cases of cerebral palsy in term infants are related to prenatal factors including fetal growth restriction, thrombotic states, placental conditions, and genetic factors. Bottom Line: More needs to be done to determine the cause of cerebral palsy so we can intervene to improve outcomes. The study of placental pathology is one way that is only now being recognized as an important parameter. Of note, the authors show that continuous electronic fetal monitoring has not reduced the incidence of cerebral palsy despite an increase in surgical deliveries. Furthermore, abnormal fetal monitoring does not predict the outcome of cerebral palsy despite expert witnesses stating that monitoring is predictive. Nelson and Blair show that we need to look carefully at prenatal factors and get away from reliance on electronic fetal monitoring, which shows little predictive value for the development of cerebral palsy. Cerebral palsy is not always associated with birth injury. We need to work with pediatricians, neonatologists, and obstetricians to achieve inroads in abolishing cerebral palsy. The fear of litigation surrounding obstetrical delivery is a distraction to the work that needs to be done.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Commentary
Short Takes Steven G. Pavlakis MD * Center for Brain and Behavior, Maimonides Medical Center, The Brooklyn Hospital Center and Icahn School of Medicine at Mount Sinai, Brooklyn, New York
Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy: an open label, dose finding, and feasibility phase1/2 trial. Lancet Neurology 14:469477, 2015
A global perspective on hypertension: a Lancet Commission. Lancet 386:637-638, 2015
Pressler RM, Boylan GB, Marlow N, et al.
Flash Summary: In this comment the authors opine that hypertension is the number one killer through cerebrovascular disease (including stroke), affecting 1 billion individuals globally. Since awareness and treatment are very low in poor and middle-income countries, The Lancet has taken the initiative to launch a commission on hypertension whose aim is to generate a campaign to implement actions to improve management of hypertension globally.
Flash Summary: The authors report the result of a dose-finding, feasibility trial studying bumetanide (a loop diuretic) in newborns with seizures after hypoxic ischemic encephalopathy. Patients who did not respond to phenobarbital were given, in addition, bumetanide. The trial was terminated early because of possible side effects. The numbers were small (n ¼ 14) and toxicity could not be proved, but there was a suggestion of ototoxicity. In addition there was treatment failure. Bottom Line: It is important that more seizure trials are performed in the newborn. Phenobarbital and phenytoin are the medications historically used with topiramate and levetiracetam gaining recent proponents. Further studies are necessary, and this study design can work with some tweaking. For example, efficacy may need to be assessed over longer time periods. The study aimed for an 80% seizure reduction in newborns on electroencephalography, but five of the newborns had no seizures before initiation of medication and as such were a failure of treatment. A phase 1 and 2 trial is not designed for efficacy, so a failure of treatment is not proved. Phase 1 and 2 are typically designed to examine only dosage and safety. There are many roadblocks to newborn trials including entrenched dogmas. In addition, there is a movement for many neonatology divisions to become independent departments and cost centers separate from pediatric departments. Therefore more political roadblocks are appearing. Nevertheless, this study is a model, after some improvements, for what can be done for our newborn patients with epilepsy. We need to actively work with neonatologists.
Editor’s note: Short Takes offers a brief analysis by Steven G. Pavlakis of selected articles that may be of interest to child neurologists. Papers that strike the fancy of the analyst or the editors are selected for inclusion, but we welcome suggestions.
* Communications should be addressed to: Dr. Pavlakis; Center for Brain and Behavior; Maimonides Medical Center; The Brooklyn Hospital Center; 121 DeKalb Avenue; Brooklyn, NY 11201. E-mail address: [email protected] 0887-8994/$ e see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2015.10.003
Olsen MH, Spencer S.
Bottom Line: Here there is no pediatric component to this Commission. There is emerging evidence that adolescent hypertension affects cerebrovascular autoregulation, cognitive function including executive function, and even white matter tracks in young adults. There is also emerging evidence that hypertension may even play a role as a risk factor in some pediatric stroke. Since there is little awareness of hypertension in the adolescent in regard to early cerebrovascular disease, I believe that it is our role to disseminate the risk of adolescent hypertension to both poor and rich countries. This is an underrecognized public health problem that deserves our attention as pediatric neurologists.
2
Short Takes / Pediatric Neurology 56 (2016) 1e2
Prenatal factors in singletons with cerebral palsy born at or near term. N Engl J Med 373:946-953, 2015 Nelson KB, Blair E. Flash Summary: Cerebral palsy has a prevalence of about 2 in 1000 children who were born at term. The prevalence has not changed over the past three decades. Here, in a review, Nelson and Blair show that most cases of cerebral palsy in term infants are related to prenatal factors including fetal growth restriction, thrombotic states, placental conditions, and genetic factors. Bottom Line: More needs to be done to determine the cause of cerebral palsy so we can intervene to improve outcomes. The study of placental pathology is one way that is only now being recognized as an important parameter. Of note, the authors show that continuous electronic fetal monitoring has not reduced the incidence of cerebral palsy despite an increase in surgical deliveries. Furthermore, abnormal fetal monitoring does not predict the outcome of cerebral palsy despite expert witnesses stating that monitoring is predictive. Nelson and Blair show that we need to look carefully at prenatal factors and get away from reliance on electronic fetal monitoring, which shows little predictive value for the development of cerebral palsy. Cerebral palsy is not always associated with birth injury. We need to work with pediatricians, neonatologists, and obstetricians to achieve inroads in abolishing cerebral palsy. The fear of litigation surrounding obstetrical delivery is a distraction to the work that needs to be done.