scholarly journals Treating Seizures after Hypoxic-Ischemic Encephalopathy—Current Controversies and Future Directions

2021 ◽  
Vol 22 (13) ◽  
pp. 7121
Author(s):  
Kelly Q. Zhou ◽  
Alice McDouall ◽  
Paul P. Drury ◽  
Christopher A. Lear ◽  
Kenta H. T. Cho ◽  
...  

Seizures are common in newborn infants with hypoxic-ischemic encephalopathy and are highly associated with adverse neurodevelopmental outcomes. The impact of seizure activity on the developing brain and the most effective way to manage these seizures remain surprisingly poorly understood, particularly in the era of therapeutic hypothermia. Critically, the extent to which seizures exacerbate brain injury or merely reflect the underlying evolution of injury is unclear. Current anticonvulsants, such as phenobarbital and phenytoin have poor efficacy and preclinical studies suggest that most anticonvulsants are associated with adverse effects on the developing brain. Levetiracetam seems to have less potential neurotoxic effects than other anticonvulsants but may not be more effective. Given that therapeutic hypothermia itself has significant anticonvulsant effects, randomized controlled trials of anticonvulsants combined with therapeutic hypothermia, are required to properly determine the safety and efficacy of these drugs. Small clinical studies suggest that prophylactic phenobarbital administration may improve neurodevelopmental outcomes compared to delayed administration; however, larger high-quality studies are required to confirm this. In conclusion, there is a distinct lack of high-quality evidence for whether and to what extent neonatal seizures exacerbate brain damage after hypoxia-ischemia and how best to manage them in the era of therapeutic hypothermia.

2021 ◽  
Vol 15 ◽  
Author(s):  
Tushar A. Shah ◽  
Haree K. Pallera ◽  
Cortney L. Kaszowski ◽  
William Thomas Bass ◽  
Frank A. Lattanzio

ObjectiveComplement activation is instrumental in the pathogenesis of Hypoxic-ischemic encephalopathy (HIE), a significant cause of neonatal mortality and disability worldwide. Therapeutic hypothermia (HT), the only available treatment for HIE, only modestly improves outcomes. Complement modulation as a therapeutic adjunct to HT has been considered, but is challenging due to the wide-ranging role of the complement system in neuroinflammation, homeostasis and neurogenesis in the developing brain. We sought to identify potential therapeutic targets by measuring the impact of treatment with HT on complement effector expression in neurons and glia in neonatal HIE, with particular emphasis on the interactions between microglia and C1q.MethodsThe Vannucci model was used to induce HIE in term-equivalent rat pups. At P10-12, pups were randomly assigned to three different treatment groups: Sham (control), normothermia (NT), and hypothermia (HT) treatment. Local and systemic complement expression and neuronal apoptosis were measured by ELISA, TUNEL and immunofluorescence labeling, and differences compared between groups.ResultsTreatment with HT is associated with decreased systemic and microglial expression of C1q, decreased systemic C5a levels, and decreased microglial and neuronal deposition of C3 and C9. The effect of HT on cytokines was variable with decreased expression of pro and anti-inflammatory effectors. HT treatment was associated with decreased C1q binding on cells undergoing apoptosis.ConclusionOur data demonstrate the extreme complexity of the immune response in neonatal HIE. We propose modulation of downstream effectors C3a and C5a as a therapeutic adjunct to HT to enhance neuroprotection in the developing brain.


2019 ◽  
Vol 34 (10) ◽  
pp. 556-566 ◽  
Author(s):  
Gwendolyn J. Gerner ◽  
Eric I. Newman ◽  
V. Joanna Burton ◽  
Brenton Roman ◽  
Elizabeth A. Cristofalo ◽  
...  

Aim: Hypoxic-ischemic encephalopathy is associated with damage to deep gray matter; however, white matter involvement has become recognized. This study explored differences between patients and clinical controls on diffusion tensor imaging, and relationships between diffusion tensor imaging and neurodevelopmental outcomes. Method: Diffusion tensor imaging was obtained for 31 neonates after hypoxic-ischemic encephalopathy treated with therapeutic hypothermia and 10 clinical controls. A subgroup of patients with hypoxic-ischemic encephalopathy (n = 14) had neurodevelopmental outcomes correlated with diffusion tensor imaging scalars. Results: Group differences in diffusion tensor imaging scalars were observed in the putamen, anterior and posterior centrum semiovale, and the splenium of the corpus callosum. Differences in these regions of interest were correlated with neurodevelopmental outcomes between ages 20 and 32 months. Conclusion: Therapeutic hypothermia may not be a complete intervention for hypoxic-ischemic encephalopathy, as neonatal white matter changes may continue to be evident, but further research is warranted. Patterns of white matter change on neonatal diffusion tensor imaging correlated with neurodevelopmental outcomes in this exploratory pilot study.


2019 ◽  
Vol 4 (3) ◽  
pp. 1-9 ◽  
Author(s):  
Jonathan Reiss ◽  
Mridu Sinha ◽  
Jeffrey Gold ◽  
Julie Bykowski ◽  
Shelley M. Lawrence

Introduction: Accurately diagnosing and treating infants with mild forms of hypoxic ischemic encephalopathy (HIE) is important, as the majority of neonates with signs and symptoms of HIE after birth do not meet clinical criteria for moderate or severe disease. Emerging evidence, however, suggests that infants with mild HIE (mHIE) have an increased risk for neurodevelopmental impairment (NDI). Methods: This retrospective descriptive study examined all inborn infants ≥35 week’s gestational age at a single, level III neonatal intensive care unit (NICU) in California between January 1, 2012, and December 31, 2015. International Classification of Diseases codes were used as a proxy to identify neonates with mHIE but who did not receive therapeutic hypothermia (TH). Short- and long-term neurodevelopmental outcomes were documented, including abnormal (1) brain magnetic resonance imaging within 10 days of birth suggestive of HIE, (2) electroencephalogram with electrographic seizures, (3) neurologic discharge examination, or (4) NDI following NICU discharge. Results: Over the 4-year study period, 25 infants met inclusion criteria. Eight of 25 (32%) infants demonstrated neurologic impairment, defined by an abnormality in at least one of the four categories. The remaining 17 infants were without documented evidence for adverse outcomes. Conclusion: Our results indicate that children with mHIE are at significant risk for neurologic injury and may benefit from more aggressive interventions. Further prospective studies should be completed to determine the efficacy of TH in this specific patient population.


2011 ◽  
Vol 68 (10) ◽  
pp. 825-831
Author(s):  
Brankica Vasiljevic ◽  
Svjetlana Maglajlic-Djukic ◽  
Sanja Stankovic ◽  
Dragana Lutovac ◽  
Miroslava Gojnic

Background/Aim. The use of color Doppler neurosonography (cD-US) allows simultaneous examination of parenchymal and vascular cerebral structures. Evaluation of cerebral blood flow velocities (CBFV) and vascular resistance are important in assessment of cerebral circulation in neonates with hypoxic ischemic encephalopathy (HIE). The aim of this study was to evaluate the predictive value of cD-US for abnormal neurodevelopmental outcome in the neonates with HIE. Methods. A total of 90 neonates (>32 weeks gestational age) with HIE were enrolled prospectively. All the neonates with HIE were categorized into three grades according to the Sarnat and Sarnat clinical staging system: mild HIE, moderate HIE, and severe HIE. cD-US was performed simultaneously during the first 24 h of life. Neurodevelopment outcome was assessed at 12 months of age in all the neonates. Resluts. The values of CBFV and the values of index resistance (RI) correlated with the severity of HIE (p < 0.0001) and subsequent neurodevelopmental outcome (p < 0.001). We detected a significant difference in values of CBFV and in values of RI between preterm and full-term neonates (p < 0.01). The cut-off value of RI for poor neurodevelopmental outcomes was 0.81. Conclusions. cD-US could be very useful and safe diagnostic tool for assessing severity of HIE and subsequent adverse neurodevelopmental outcome.


2022 ◽  
Author(s):  
Adnan Hadid ◽  
Taher AL-Shantout ◽  
Rayan Terkawi ◽  
Baraa Aldbes ◽  
Manal Zahran ◽  
...  

Abstract Background: Telemedicine is widely used in neonatal services in developed countries. Lack of expertise and/or facilities, however, limited its use in developing countries and around areas of military conflicts. To our knowledge, no reports are demonstrating the feasibility of administering therapeutic hypothermia (TH) through telemedicine to neonates with hypoxic-ischemic encephalopathy (HIE) in resource-limited areas.Methodology: This is a retrospective study, evaluating 22 patients who received TH, guided by telemedicine, through a mobile app (Telegram®). We assessed the feasibility of utilizing Telemedicine in guiding the application of TH to infants affected with HIE in the North-West of Syria between July 2020 and July 2021.Results: Out of 5,545 newborn infants delivered during the study period, 22 patients were eligible for TH guided by Telemedicine. Patients were referred for consultation at a median (IQR) of 137 (35-165) minutes of life. A median (IQR) of 12 (3-18) minutes elapsed between the call for a consultation and the consultant response, and a median (IQR) of 30 (0-42) minutes elapsed between seeking the consultation and the initiation of cooling therapy. Eighteen patients completed cooling for 72 hours. The patients' temperatures were within the target range (33-34°C) most of the time (84.1%).Conclusion: Telemedicine is a feasible method to guide the implementation TH for HIE in resource-limited areas. The short-term success rate is relatively high; however, further studies with a larger population are needed to confirm these findings.


2021 ◽  
Vol 6 (1) ◽  
pp. 88-93
Author(s):  
A. A. Zarubin ◽  
E. S. Filippov ◽  
A. S. Vanyarkina ◽  
O. G. Ivanova ◽  
A. A. Shishkina

Background. Newborn infants who have undergone severe birth asphyxia have a high risk of neurological disorders and death. The most effective method for the treatment of hypoxic ischemic encephalopathy caused by intrapartum asphyxia is therapeutic hypothermia, or targeted temperature management. Currently, there are no large studies comparing its different methods, therefore the aim of our study was to compare the effectiveness of device-induced and uncontrolled therapeutic hypothermia in newborn infants who underwent intrapartum asphyxia.Materials and methods. Study design: we conducted a retrospective, longitudinal, cohort study in 39 newborn infants born in severe asphyxia and receiving uncontrolled therapeutic hypothermia (group 1), and in 48 newborn infants born in severe asphyxia and receiving device-induced therapeutic hypothermia (group 2). Statistical data processing was carried out using standard techniques.Results. The body temperature in newborn infants of both groups was reduced to 33.5 °C within the first hour, but when using uncontrolled therapeutic hypothermia, the body temperature fluctuated from 32 to 35 °C. Device-induced therapeutic hypothermia has a more effective neuroprotective effect as compared to uncontrolled hypothermia (p< 0.05) and more rapidly stabilizes metabolism in newborns due to a decrease in lactate levels (p < 0.05). In newborns device-induced therapeutic hypothermia stabilizes hemodynamics more quickly compared to uncontrolled therapeutic hypothermia (p < 0.05). Device-induced therapeutic hypothermia reduces the period of hospitalization in the neonatal intensive care unit (p < 0.05), the risk of cerebral edema (p < 0.05) and of the repeated episodes of seizures (p < 0.05). Conclusion. Using uncontrolled therapeutic hypothermia causes a high risk of unintentional fluctuations in rectal temperature towards both hypothermia and rewarming, which can aggravate the severe condition of newborn infants. Device-induced therapeutic hypothermia has a more effective neuroprotective effect.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zheng Wang ◽  
Peng Zhang ◽  
Wenhao Zhou ◽  
Shiwen Xia ◽  
Wei Zhou ◽  
...  

Abstract Background Neonatal hypoxic-ischemic encephalopathy (HIE) affects as many as 100,000 infants each year in China. Therapeutic hypothermia reduces HIE related mortality and long-term neurodevelopmental disabilities. National guidelines for HIE management were published a decade ago. This study aimed to investigate the current status of HIE diagnosis and treatment in China. Method This prospective cross-sectional national survey used a questionnaire evaluating practices related to HIE management. Descriptive statistics and Chi-square or Fisher’s exact test were used, and a p-value of < 0.05 was considered significant. Results The 273 hospitals that completed the survey were located in 31 of the 34 provincial districts in China. Eighty-eight percent of the hospitals were Level III hospitals, and 74% treated 10 or more HIE cases annually. Awareness rates of the national guidelines for HIE diagnosis, HIE treatment, and therapeutic hypothermia protocol were 85, 63, and 78%, respectively. Neurological manifestations and blood gas were used as HIE diagnostic criteria by 96% (263/273) and 68% (186/273) of the hospitals, respectively. Therapeutic hypothermia was used in 54% (147/273) of hospitals. The percentage of general hospitals that implemented therapeutic hypothermia (43%, 71/165) was significantly lower than that in maternity and infant hospitals (67%, 49/73) (χ2 = 11.752, p = 0.001) and children’s hospitals (77%, 27/35) (χ2 = 13.446, p < 0.001). Reasons for not providing therapeutic hypothermia included reduction of HIE cases in recent years (39%), high cost of cooling devices and treatment (31%), lack of training (26%), and safety concerns (4%). Among the hospitals that provided therapeutic hypothermia, 27% (39/147) were in full compliance with the recommended protocol. Eighty-one percent (222/273) of the hospitals treated HIE infants with putative neuroprotective agents alone or in combination with cooling. Ninety-one percent of the hospitals had long-term neurodevelopmental follow-up programs for infants with HIE. Conclusions There is significant heterogeneity in HIE diagnosis and treatment in China. Therapeutic hypothermia has not become a standard of care for neonatal HIE nationwide. Unproven agents are widely used for HIE treatment. Nationwide standardization of HIE management and dissemination of therapeutic hypothermia represent the opportunities to reduce mortality and improve long-term neurodevelopmental outcomes of children affected by HIE.


2020 ◽  
Vol 174 (1) ◽  
pp. 48 ◽  
Author(s):  
Mikael Finder ◽  
Geraldine B. Boylan ◽  
Deirdre Twomey ◽  
Caroline Ahearne ◽  
Deirdre M. Murray ◽  
...  

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