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Wusthoff CJ, Numis AL, Pressler RM, Chu CJ, Massey S, Clancy RR, Nguyen S, Hahn CD, Scher MS, Pilon B, King DT, Wong HN, Tsuchida TN, Riviello JJ, Shellhaas RA. The American Clinical Neurophysiology Society Guideline on Indications for Continuous Electroencephalography Monitoring in Neonates. J Clin Neurophysiol 2025; 42:1-11. [PMID: 39752571 DOI: 10.1097/wnp.0000000000001120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Indexed: 01/11/2025] Open
Abstract
PURPOSE Continuous EEG (cEEG) monitoring is increasingly used in the management of neonates with seizures. There remains debate on what clinically relevant information can be gained from cEEG in neonates with suspected seizures, at high risk for seizures, or with definite seizures, as well as the use of cEEG for prognosis in a variety of conditions. In this guideline, we address these questions using American Clinical Neurophysiology Society structured methodology for clinical guideline development. METHODS A working group was formed from American Clinical Neurophysiology Society membership with expertise in neonatal cEEG and a set of priority questions developed. We performed literature searches in PubMed and EMBASE to identify relevant studies. Evidence tables were compiled from extracted data and quality assessments performed. A modification of the GRADE process was used to evaluate the body of evidence and draft recommendations. RESULTS Our working group identified six priority questions to evaluate the accuracy of cEEG for neonatal seizure diagnosis and the formulation of prognosis. An initial literature search yielded 18,167 results, which were distilled to a set of 217 articles. Overall, the quality of evidence for most priority questions was rated as very low and we provided conditional recommendations based on published literature and expert consensus. For each priority question, we also considered the benefits and harms of cEEG, with relative harms considered to be far less than the potential benefits across recommendations. CONCLUSIONS We present evidence-based clinical guidelines regarding indications for cEEG monitoring in neonates. Considering resource utilization and feasibility, when cEEG monitoring results have a likelihood of altering clinical decision making, the authors felt the resource investment was justifiable.
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Affiliation(s)
| | - Adam L Numis
- Department of Neurology and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA
| | - Ronit M Pressler
- Clinical Neuroscience, UCL-Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, Great Britain
| | - Catherine J Chu
- Divisions of Child Neurology and Neurophysiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Shavonne Massey
- Departments of Neurology and Pediatrics, University of Pennsylvania, and the Children's Hospital of Philadelphia, Philadelphia, PA
| | - Robert R Clancy
- Departments of Neurology and Pediatrics, University of Pennsylvania, and the Children's Hospital of Philadelphia, Philadelphia, PA
| | | | - Cecil D Hahn
- Division of Neurology, The Hospital for Sick Children and Department of Paediatrics, University of Toronto, Toronto, Canada
| | - Mark S Scher
- Case Western Reserve University School of Medicine, Cleveland, OH
| | | | | | - Hong-Nei Wong
- Lane Medical Library, Stanford University School of Medicine, Palo Alto, CA
| | - Tammy N Tsuchida
- Departments of Neurology and Pediatrics, George Washington University School of Medicine and Health Sciences, Children's National Hospital, Washington, DC
| | - James J Riviello
- Division of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine/Texas Children's Hospita, Houston, TX; and
| | - Renée A Shellhaas
- Department of Neurology, Washington University in St Louis, St. Louis, MO
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Cappellari AM, Palumbo S, Margiotta S. Questions and Controversies in Neonatal Seizures. CHILDREN (BASEL, SWITZERLAND) 2023; 11:40. [PMID: 38255354 PMCID: PMC10814600 DOI: 10.3390/children11010040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/21/2023] [Accepted: 12/26/2023] [Indexed: 01/24/2024]
Abstract
Neonatal seizures are relatively common, but their diagnosis and management remain challenging. We reviewed the scientific literature on neonatal seizures from July 1973 to November 2023. Several parameters were considered, including pathophysiology, diagnostic criteria, electroencephalographic findings and treatment. Recent classification system of seizures and epilepsies in the newborn, as well as treatment recommendations of neonatal seizures, have been proposed. Nonetheless, the approach to neonatal seizures varies among clinicians and centres, including detection, investigation, treatment and follow-up of patients. There are still many issues on the diagnosis and treatment of neonatal seizures, including the meaning or relevance of some electroencephalographic findings, the precise estimation of the seizure burden, the limited efficacy and side effects risk of antiseizure medications, and the best measures to establish the outcome.
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Affiliation(s)
- Alberto M. Cappellari
- Department of Neuroscience and Mental Health, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy
| | - Sarah Palumbo
- Postgraduate School of Paediatrics, Department of Pediatrics, University of Milan, 20122 Milano, Italy; (S.P.); (S.M.)
| | - Stefania Margiotta
- Postgraduate School of Paediatrics, Department of Pediatrics, University of Milan, 20122 Milano, Italy; (S.P.); (S.M.)
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Pressler RM, Abend NS, Auvin S, Boylan G, Brigo F, Cilio MR, De Vries LS, Elia M, Espeche A, Hahn CD, Inder T, Jette N, Kakooza-Mwesige A, Mader S, Mizrahi EM, Moshé SL, Nagarajan L, Noyman I, Nunes ML, Samia P, Shany E, Shellhaas RA, Subota A, Triki CC, Tsuchida T, Vinayan KP, Wilmshurst JM, Yozawitz EG, Hartmann H. Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures. Epilepsia 2023; 64:2550-2570. [PMID: 37655702 DOI: 10.1111/epi.17745] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 08/09/2023] [Accepted: 08/10/2023] [Indexed: 09/02/2023]
Abstract
Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.
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Affiliation(s)
- Ronit M Pressler
- Clinical Neuroscience, UCL-Great Ormond Street Institute of Child Health, London, UK
- Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
| | - Nicholas S Abend
- Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Stéphan Auvin
- Department Medico-Universitaire Innovation Robert-Debré, Robert Debré Hospital, Public Hospital Network of Paris, Pediatric Neurology, University of Paris, Paris, France
| | - Geraldine Boylan
- INFANT Research Centre, University College Cork, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - Francesco Brigo
- Department of Neurology, Hospital of Merano (SABES-ASDAA), Merano, Italy
- Innovation Research and Teaching Service (SABES-ASDAA), Teaching Hospital of Paracelsus Medical Private University, Bolzano-Bozen, Italy
| | - Maria Roberta Cilio
- Division of Pediatric Neurology, Saint-Luc University Hospital, and Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium
| | - Linda S De Vries
- Department of Neonatology, University Medical Center, Utrecht, the Netherlands
| | - Maurizio Elia
- Unit of Neurology and Clinical Neurophysiopathology, Oasi Research Institute-IRCCS, Troina, Italy
| | - Alberto Espeche
- Department of Neurology, Hospital Materno Infantil, Salta, Argentina
| | - Cecil D Hahn
- Department of Pediatrics, Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Terrie Inder
- Department of Pediatrics, Newborn Medicine, Children's Hospital of Orange County, University of California, Irvine, Irvine, California, USA
| | - Nathalie Jette
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Angelina Kakooza-Mwesige
- Department of Pediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
| | - Silke Mader
- Scientific Affairs, European Foundation for the Care of Newborn Infants, Munich, Germany
| | - Eli M Mizrahi
- Departments of Neurology and Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Solomon L Moshé
- Isabelle Rapin Division of Child Neurology, Saul R. Korey Department of Neurology, Montefiore Medical Center, Bronx, New York, USA
- Departments of Neuroscience and Pediatrics, Albert Einstein College of Medicine, and Montefiore Medical Center, Bronx, New York, USA
| | - Lakshmi Nagarajan
- Children's Neuroscience Service, Department of Neurology, Perth Children's Hospital and University of Western Australia, Nedlands, Western Australia, Australia
| | - Iris Noyman
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
- Pediatric Neurology Unit, Pediatric Division, Soroka Medical Center, Beer-Sheva, Israel
| | - Magda L Nunes
- Pontifícia Universidade Católica do Rio Grande do Sul-PUCRS School of Medicine and the Brain Institute, Porto Alegre, Brazil
| | - Pauline Samia
- Departments of Pediatrics and Child Health, Aga Khan University, Nairobi, Kenya
- Department of Public Health and Primary Care, Ghent University, Ghent, Belgium
| | - Eilon Shany
- Department of Neonatology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Renée A Shellhaas
- Department of Neurology, Washington University, St. Louis, Missouri, USA
| | - Ann Subota
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Chahnez Charfi Triki
- Child Neurology Department, Hedi Chaker Hospital, Sfax Medical School, University of Sfax, Sfax, Tunisia
| | - Tammy Tsuchida
- Departments of Neurology and Pediatrics, Children's National Health System, George Washington University School of Medicine, Washington, District of Columbia, USA
| | | | - Jo M Wilmshurst
- Department of Paediatric Neurology, Red Cross War Memorial Children's Hospital, Neuroscience Institute, University of Cape Town, Cape Town, South Africa
| | - Elissa G Yozawitz
- Isabelle Rapin Division of Child Neurology, Saul R. Korey Department of Neurology, Montefiore Medical Center, Bronx, New York, USA
| | - Hans Hartmann
- Clinic for Pediatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, Hannover, Germany
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Levetiracetam versus Phenobarbital for Neonatal Seizures: A Retrospective Cohort Study. Pediatr Neurol 2023; 138:62-70. [PMID: 36401982 DOI: 10.1016/j.pediatrneurol.2022.10.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 08/22/2022] [Accepted: 10/15/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Although phenobarbital (PB) is commonly used as a first-line antiseizure medication (ASM) for neonatal seizures, in 2015 we chose to replace it with levetiracetam (LEV), a third-generation ASM. Here, we compared the safety and efficacy of LEV and PB as first-line ASM, considering the years before and after modifying our treatment protocol. METHODS We conducted a retrospective cohort study of 108 neonates with electroencephalography (EEG)-confirmed seizures treated with first-line LEV or PB in 2012 to 2020. RESULTS First-line ASM was LEV in 33 (31%) and PB in 75 (69%) neonates. The etiology included acute symptomatic seizures in 69% of cases (30% hypoxic-ischemic encephalopathy, 32% structural vascular, 6% infectious, otherwise metabolic) and neonatal epilepsy in 22% (5% structural due to brain malformation, 17% genetic). Forty-two of 108 (39%) neonates reached seizure freedom following first-line therapy. Treatment response did not vary by first-line ASM among all neonates, those with acute symptomatic seizures, or those with neonatal-onset epilepsy. Treatment response was lowest for neonates with a higher seizure frequency, particularly for those with status epilepticus versus rare seizures (P < 0.001), irrespective of gestational age, etiology, or EEG findings. Adverse events were noted in 22 neonates treated with PB and in only one treated with LEV (P < 0.001). CONCLUSIONS Our study suggests a potential noninferiority and a more acceptable safety profile for LEV, which may thus be a reasonable option as first-line ASM for neonatal seizures in place of PB. Treatment should be initiated as early as possible since higher seizure frequencies predispose to less favorable responses.
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Hashish M, Bassiouny MR. Neonatal seizures: stepping outside the comfort zone. Clin Exp Pediatr 2022; 65:521-528. [PMID: 35381172 PMCID: PMC9650361 DOI: 10.3345/cep.2022.00115] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 03/22/2022] [Indexed: 11/27/2022] Open
Abstract
Seizures are the most common neurological disorders in newborns. Managing neonatal seizures is challenging, especially for neurologists who are not neonatal specialists. Acute brain injury during ischemic insult is a key component of seizure occurrence, while genetic and metabolic disorders play less prevalent but more severe roles. The diagnosis of neonatal seizure is ambiguous, as the subjective differentiation between seizure and nonepileptic events is difficult; therefore, electrographic recording is the gold standard for diagnosis. The detection of electrographic seizures by neonatologists is currently facilitated by amplitude-integrated electroencephalography availability in many neonatal intensive care units. Although it is less sensitive than conventional electroencephalography, it is better to record all risky neonates to filter the abnormal events as early as possible to enable the initiation of dedicated therapy at proper dose and time and facilitate the initial response to antiepileptic drugs. This, in turn, helps maintain the balance between unnecessary drug use and their neurotoxic effects. Moreover, the early treatment of electrographic seizures plays a vital role in the suppression of subsequent abnormal brain electricity (status epilepticus) and shortening the hospital stay. An explicit understanding of seizure etiology and pathophysiology should direct attention to the proper prescription of short- and long-term antiepileptic medications to solve the challenging issue of whether neonatal seizures progress to postneonatal epilepsy and long-term cognitive deficits. This review addresses recent updates in different aspects of neonatal seizures, particularly electrographic discharge, including their definition, etiology, classification, diagnosis, management, and neurodevelopmental outcomes.
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Affiliation(s)
- Menna Hashish
- Neonatal Intensive Care Unit, Mansoura University Children's Hospital, Mansoura, Egypt
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Verwoerd C, Limjoco J, Rajamanickam V, Knox A. Efficacy of Levetiracetam and Phenobarbital as First-Line Treatment for Neonatal Seizures. J Child Neurol 2022; 37:401-409. [PMID: 35311411 DOI: 10.1177/08830738221086107] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
High neonatal seizure burden is associated with worsened neurodevelopmental outcomes. We compared the efficacy of initial treatment with levetiracetam vs phenobarbital for maintaining low seizure burden in a retrospective cohort of 25 neonates monitored with video electroencephalography (EEG). Video EEG tracing were reviewed and paired with medication bolus times to determine seizure burden after treatment. Initial cumulative dose of phenobarbital was 20 mg/kg in all but 1 case; initial cumulative dose of levetiracetam ranged from 50 to 100 mg/kg. Eleven of 17 (65%) patients sustained seizure burden <10% following initial treatment with levetiracetam, compared with 5 of 8 (63%) with phenobarbital. Thirteen (76%) patients treated with levetiracetam had sustained seizure burden <20% compared with 6 (75%) treated with phenobarbital. The phenobarbital group showed a larger absolute reduction in average seizure burden in the hour before and after treatment (-24.3 vs -14.2 minutes/h). Six of 17 (35%) patients treated with levetiracetam remained seizure free after initial treatment, compared with 2 of 8 (25%) patients treated with phenobarbital. Initial treatment with levetiracetam was associated with shorter average time to seizure freedom (15 vs 21 hours). None of these results were statistically significant. Cumulative doses of levetiracetam 100 mg/kg were well tolerated and associated with substantial decrease in seizure burden in several cases. Levetiracetam remains a promising first-line treatment for neonatal seizures; additional randomized controlled trials evaluating the effects of high-dose levetiracetam on seizure burden and long-term outcomes are warranted.
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Affiliation(s)
- Carmen Verwoerd
- Department of Pediatrics, Division of Neonatology, 5228University of Wisconsin, Madison, WI, USA
| | - Jamie Limjoco
- Department of Pediatrics, Division of Neonatology, 5228University of Wisconsin, Madison, WI, USA
| | - Victoria Rajamanickam
- Department of Biostatistics and Medical Informatices, 5228University of Wisconsin, Madison, WI, USA
| | - Andrew Knox
- Department of Neurology, Division of Pediatric Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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Keene JC, Wainwright M, Morgan LA, Mietzsch U, Musa N, Bozarth XL, Natarajan N. Retrospective Evaluation of First-line Levetiracetam use for Neonatal Seizures after Congenital Heart Defect repair with or without Extracorporeal Membrane Oxygenation. J Pediatr Pharmacol Ther 2022; 27:254-262. [PMID: 35350164 DOI: 10.5863/1551-6776-27.3.254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 07/17/2021] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Levetiracetam (LEV) efficacy for neonatal seizures is debated. We evaluated LEV as a first line anti-seizure medicine (ASM) in neonates following neonatal congenital heart defect (CHD) repair who did not require extracorporeal membrane oxygenation (ECMO) vs neonates who required ECMO. METHODS A single center retrospective review of neonates with CHD from 2015 to 2020 was conducted. Neonates were included if seizures were present on continuous EEG after CHD repair either on or off ECMO, and they received LEV as a first line ASM. Primary outcomes were seizure resolution with LEV, adverse events and response to subsequent ASM. RESULTS Eighteen total neonates were evaluated, 10 with seizures post-CHD repair who did not require ECMO and 8 who required ECMO. In the non-ECMO cohort, nine of ten were successfully treated with LEV monotherapy with no adverse events. In comparison, the eight neonates who required ECMO had a higher initial seizure burden (1.6% vs 17%, p=0.003), were more likely to have injury on neuroimaging (12.5 vs 75%, p= 0.04), and all neonates required multiple ASMs. Seizure burden did not decrease with LEV, but significantly decreased with phenobarbital and fosphenytoin (14.4% and 10.5%, p = 0.024). CONCLUSIONS Neonates with CHD and seizures on and off ECMO demonstrated divergent seizure characteristics including seizure burden and response to LEV. LEV may reduce neonatal seizure burden after uncomplicated CHD repair. However, in neonates requiring ECMO, multiple ASMs were required. A prospective evaluation of ASM efficacy and safety in this high-risk population is urgently needed.
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Affiliation(s)
- Jennifer C Keene
- University of Washington, Department of Neurology, Division of Child Neurology (JK, MW, LM, XB, NN), Seattle, WA
| | - Mark Wainwright
- University of Washington, Department of Neurology, Division of Child Neurology (JK, MW, LM, XB, NN), Seattle, WA
| | - Lindsey A Morgan
- University of Washington, Department of Neurology, Division of Child Neurology (JK, MW, LM, XB, NN), Seattle, WA
| | | | - Ndidi Musa
- Division of Pediatric Critical Care Medicine (NM), Seattle, WA
| | - Xiuhua L Bozarth
- University of Washington, Department of Neurology, Division of Child Neurology (JK, MW, LM, XB, NN), Seattle, WA
| | - Niranjana Natarajan
- University of Washington, Department of Neurology, Division of Child Neurology (JK, MW, LM, XB, NN), Seattle, WA
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Association between anti-seizure medication and outcomes in infants. J Perinatol 2022; 42:359-364. [PMID: 34671100 DOI: 10.1038/s41372-021-01240-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 09/28/2021] [Accepted: 10/06/2021] [Indexed: 11/09/2022]
Abstract
OBJECTIVE To compare treatment failure between: (1) infants treated with phenobarbital versus levetiracetam for first-line treatment and (2) infants treated with phenytoin versus levetiracetam for second-line treatment following phenobarbital. STUDY DESIGN This retrospective cohort study included infants with seizures receiving phenobarbital or levetiracetam as the initial anti-seizure medication. Treatment failure was defined as the need for additional anti-seizure medication within 24-72 h and compared using mixed-effect logistic regression after adjustment for confounding factors, including center. RESULTS In this cohort of 6842 infants, the incidence of treatment failure was 31% vs. 38% in infants receiving first-line phenobarbital versus levetiracetam (adjusted OR: 0.70; 95% CI 0.58-0.84). There was no significant difference in second-line treatment failure (adjusted OR: 1.31; 95% CI 0.92-1.86). CONCLUSIONS First-line treatment of neonatal seizures with phenobarbital is associated with a lower rate of treatment failure than levetiracetam. There was no significant difference in second-line treatment failure.
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Keene JC, Morgan LA, Abend NS, Bates SV, Bauer Huang SL, Chang T, Chu CJ, Glass HC, Massey SL, Ostrander B, Pardo AC, Press CA, Soul JS, Shellhaas RA, Thomas C, Natarajan N. Treatment of Neonatal Seizures: Comparison of Treatment Pathways From 11 Neonatal Intensive Care Units. Pediatr Neurol 2022; 128:67-74. [PMID: 34750046 DOI: 10.1016/j.pediatrneurol.2021.10.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 09/12/2021] [Accepted: 10/04/2021] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Seizures are a common neonatal neurologic emergency. Many centers have developed pathways to optimize management. We evaluated neonatal seizure management pathways at level IV neonatal intensive care units (NICUs) in the United States to highlight areas of consensus and describe aspects of variability. METHODS We conducted a descriptive analysis of 11 neonatal seizure management pathways from level IV NICUs that specialize in neonatal neurocritical care including guidelines for electroencephalography (EEG) monitoring, antiseizure medication (ASM) choice, timing, and dose. RESULTS Study center NICUs had a median of 70 beds (interquartile range: 52-96). All sites had 24/7 conventional EEG initiation, monitoring, and review capability. Management pathways uniformly included prompt EEG confirmation of seizures. Most pathways included a provision for intravenous benzodiazepine administration if either EEG or loading of ASM was delayed. Phenobarbital 20 mg/kg IV was the first-line ASM in all pathways. Pathways included either fosphenytoin or levetiracetam as the second-line ASM with variable dosing. Third-line ASMs were most commonly fosphenytoin or levetiracetam, with alternatives including topiramate or lacosamide. All pathways provided escalation to continuous midazolam infusion with variable dosing for seizures refractory to initial medication trials. Three pathways also included lidocaine infusion. Nine pathways discussed ASM discontinuation after resolution of acute symptomatic seizures with variable timing. CONCLUSIONS Despite a paucity of data from controlled trials regarding optimal neonatal seizure management, there are areas of broad agreement among institutional pathways. Areas of substantial heterogeneity that require further research include optimal second-line ASM, dosage, and timing of ASM discontinuation.
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Affiliation(s)
- Jennifer C Keene
- Division of Pediatric Neurology, Departments of Neurology and Pediatrics, University of Washington, Seattle Children's Hospital, Seattle, Washington.
| | - Lindsey A Morgan
- Division of Pediatric Neurology, Departments of Neurology and Pediatrics, University of Washington, Seattle Children's Hospital, Seattle, Washington
| | - Nicholas S Abend
- Division of Neurology, Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
| | - Sara V Bates
- Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Sarah L Bauer Huang
- Division of Pediatric & Developmental Neurology, Department of Neurology, Washington University in St. Louis, St. Louis, Missouri
| | - Taeun Chang
- Neurology, Children's National Hospital, George Washington University, Washington, District of Columbia
| | - Catherine J Chu
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Hannah C Glass
- Department of Neurology and Weill Institute for Neuroscience, University of California, San Francisco, San Francisco, California; Department of Pediatrics, UCSF Benioff Children's Hospital, San Francisco, San Francisco, California
| | - Shavonne L Massey
- Division of Neurology, Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
| | - Betsy Ostrander
- Division of Pediatric Neurology, Department of Pediatrics, University of Utah, Salt Lake City, Utah
| | - Andrea C Pardo
- Ann & Robert H. Lurie Children's Hospital, Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
| | - Craig A Press
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado
| | - Janet S Soul
- Department of Neurology, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts
| | - Renée A Shellhaas
- Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, Michigan
| | - Cameron Thomas
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Niranjana Natarajan
- Division of Pediatric Neurology, Departments of Neurology and Pediatrics, University of Washington, Seattle Children's Hospital, Seattle, Washington
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Vesoulis ZA, Alexopoulos D, Rogers C, Neil J, Smyser C. Seizure burden in preterm infants and smaller brain volume at term-equivalent age. Pediatr Res 2022; 91:955-961. [PMID: 33903729 PMCID: PMC8546006 DOI: 10.1038/s41390-021-01542-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 04/02/2021] [Accepted: 04/05/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Seizures are underrecognized in preterm infants, and little is known about their impact on brain growth. We aimed to define the association between early seizures and subsequent brain growth. METHODS Infants <30 weeks gestation underwent 72 h of prospective amplitude-integrated electroencephalography (aEEG) monitoring, term-equivalent age (TEA) magnetic resonance imaging (MRI), and 2-year neurodevelopmental testing. Seizures were defined as trains of sharp waves >10 s, evolving in frequency/amplitude/morphology, and identified using automated algorithms with manual review. Using T2-weighted images, cortical surface area (CSA) and gyrification index (GI) were calculated and volumes were segmented into five tissue classes: cerebrospinal fluid, gray matter, white matter (WM), deep nuclear gray matter, and cerebellum. Correlations between total seizure burden and tissue-specific volumes were evaluated, controlling for clinical variables of interest. RESULTS Ninety-nine infants underwent aEEG/MRI assessments (mean GA = 26.3 weeks, birthweight = 899 g). Seizure incidence was 55% with a median of two events; median length = 66 s and mean burden = 285 s. Greater seizure burden was associated with smaller CSA and volumes across all tissue types, most prominently in WM (R2 = -0.603, p < 0.01), even after controlling for confounders. There was no association with GI. CONCLUSIONS Seizures in preterm infants are common and associated with smaller TEA brain volumes. This relationship was strongest for WM and independent of clinical factors. IMPACT Seizures in preterm infants are common. Little is known about the association between early seizures and later brain growth. Greater seizure burden is linked with smaller volumes of all brain tissue types, most prominently the WM. This relationship is true even controlling for other factors. Additional study is needed to identify the optimal EEG monitoring and seizure treatment strategy for improved brain growth and neurodevelopmental outcomes.
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Affiliation(s)
- Zachary A Vesoulis
- Division of Newborn Medicine, Department of Pediatrics, Washington University, St. Louis, MO, USA.
| | - Dimitrios Alexopoulos
- Division of Child Neurology, Department of Neurology, Washington University, St. Louis, MO, USA
| | - Cynthia Rogers
- Division of Newborn Medicine, Department of Pediatrics, Washington University, St. Louis, MO, USA
- Department of Psychiatry, Washington University, St. Louis, MO, USA
| | - Jeffrey Neil
- Division of Newborn Medicine, Department of Pediatrics, Washington University, St. Louis, MO, USA
- Division of Child Neurology, Department of Neurology, Washington University, St. Louis, MO, USA
- Department of Radiology, Washington University, St. Louis, MO, USA
| | - Christopher Smyser
- Division of Newborn Medicine, Department of Pediatrics, Washington University, St. Louis, MO, USA
- Division of Child Neurology, Department of Neurology, Washington University, St. Louis, MO, USA
- Department of Radiology, Washington University, St. Louis, MO, USA
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11
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Qiao MY, Cui HT, Zhao LZ, Miao JK, Chen QX. Efficacy and Safety of Levetiracetam vs. Phenobarbital for Neonatal Seizures: A Systematic Review and Meta-Analysis. Front Neurol 2021; 12:747745. [PMID: 34867732 PMCID: PMC8636327 DOI: 10.3389/fneur.2021.747745] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 09/30/2021] [Indexed: 01/10/2023] Open
Abstract
Background: Neonatal seizures are a common neurological emergency in newborns. Phenobarbital (PB) is the first-line antiepileptic drug (AED). However, PB has some side effects, such as hypotension and respiratory depression, and it can accelerate neuronal apoptosis in the immature brain. Levetiracetam (LEV), a new antiepileptic drug, has been used as a second-line drug for the treatment of neonatal seizures. Compared with PB, LEV has many advantages, including a low incidence of side effects and better neurodevelopmental outcomes. However, there are only a few systematic reviews of LEV for the treatment of neonatal seizures. Objective: To evaluate the efficacy and safety of LEV for neonatal seizures and to compare the efficacy, side effects, and neurological outcomes between LEV and PB in the treatment of neonatal seizures. Methods: The keywords LEV, PB, and neonatal seizure were searched in the MEDLINE, Cochrane Library, Web of Science, EMBASE, clinicaltrials.gov, and China National Knowledge Internet (CNKI) databases with a last update in July 2021 to collect high-quality studies. We collected studies studying the efficacy or safety of LEV and PB in the treatment of neonatal seizures applying strict inclusion and exclusion criteria. The data were extracted and outcome measures, including efficacy, side effect rate, neurological score, and mortality rate, were analyzed with RevMan 5.3 software. Results: Ten articles were finally included in the meta-analysis. The meta-analysis showed that there was no difference in efficacy between LEV and PB in the treatment of neonatal seizures. Compared with PB, the incidence of side effects of LEV was lower. The incidence of hypotension and respiratory depression in the LEV group was significantly lower than that in the PB group. In terms of long-term neurodevelopmental outcomes, there was no significant difference in the Bayley Scales of Infant Development (BSID) scores between LEV and PB. Conclusion: PB is still the first-line AED recommended by the WHO for the treatment of neonatal seizures. The new AEDs LEV may not have better efficacy than PB. At the same time, LEV is associated with better neurodevelopment outcomes and a lower risk of adverse effects. In addition, continuous EEG monitoring should be used to diagnose neonatal seizures to evaluate the severity of the seizures, remission, and drug efficacy. Systematic Review Registration: PROSPERO, identifier: CRD42021279029.
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Affiliation(s)
- Meng-Yuan Qiao
- Chongqing Traditional Chinese Medicine Hospital, Chongqing, China
| | - Hong-Tao Cui
- Chongqing Traditional Chinese Medicine Hospital, Chongqing, China.,Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Ling-Zhi Zhao
- Chongqing Traditional Chinese Medicine Hospital, Chongqing, China
| | - Jing-Kun Miao
- Chongqing Health Center for Women and Children, Chongqing, China
| | - Qi-Xiong Chen
- Chongqing Traditional Chinese Medicine Hospital, Chongqing, China
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12
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Kanmaz S, Altun Köroğlu Ö, Terek D, Serin HM, Simsek E, Dokurel Cetin İ, Yilmaz S, Yalaz M, Aktan G, Akisu M, Kultursay N, Gokben S, Tekgul H. Efficacy of levetiracetam as first-line therapy for neonatal clinical seizures and neurodevelopmental outcome at 12 months of age. Acta Neurol Belg 2021; 121:1495-1503. [PMID: 32424740 DOI: 10.1007/s13760-020-01366-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 04/24/2020] [Indexed: 10/24/2022]
Abstract
Appropriate treatment of neonatal seizures with an effective therapy is important in reducing long-term neurologic disabilities. Sixty-seven neonates, who received intravenous (IV) levetiracetam (LEV) as first-line therapy for treating seizures between 2013 and 2017 were evaluated retrospectively to investigate the efficacy of LEV and its neurodevelopmental outcome at 12 months of age. Of the 67 neonates (44 preterm and 23 term babies) evaluated for seizures, 55 (82%) had a defined etiology. EEG confirmation was obtained in 36 (57.1%) of the neonates with clinical seizures. On the 7th day of the treatment (mean seizure control time 7.4 ± 15.1 days), LEV was effective as monotherapy in 43 (64%), whereas add-on therapy was required in 24 (36%) neonates. At the 1-year follow-up, 76% of infants achieved drug-free state, nine (18%) infants remained on LEV monotherapy and three (6%) needed add-on therapy. Neurodevelopmental outcome of the infants was assessed with Ankara Development Screening Inventory and results suggested favorable neurodevelopmental outcome in 69.7% of the infants with at the end of the 1-year follow-up with LEV monotherapy. In conclusion, this retrospective cross-sectional study demonstrated that IV LEV is an effective first-line therapy for treating neonatal clinical seizures and LEV monotherapy effect was sustained during the first year follow-up.
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13
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Kirmani BF, Au K, Ayari L, John M, Shetty P, Delorenzo RJ. Super-Refractory Status Epilepticus: Prognosis and Recent Advances in Management. Aging Dis 2021; 12:1097-1119. [PMID: 34221552 PMCID: PMC8219503 DOI: 10.14336/ad.2021.0302] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 03/02/2021] [Indexed: 12/12/2022] Open
Abstract
Super-refractory status epilepticus (SRSE) is a life-threatening neurological emergency with high morbidity and mortality. It is defined as “status epilepticus (SE) that continues or recurs 24 hours or more after the onset of anesthesia, including those cases in which SE recurs on the reduction or withdrawal of anesthesia.” This condition is resistant to normal protocols used in the treatment of status epilepticus and exposes patients to increased risks of neuronal death, neuronal injury, and disruption of neuronal networks if not treated in a timely manner. It is mainly seen in patients with severe acute onset brain injury or presentation of new-onset refractory status epilepticus (NORSE). The mortality, neurological deficits, and functional impairments are significant depending on the duration of status epilepticus and the resultant brain damage. Research is underway to find the cure for this devastating neurological condition. In this review, we will discuss the wide range of therapies used in the management of SRSE, provide suggestions regarding its treatment, and comment on future directions. The therapies evaluated include traditional and alternative anesthetic agents with antiepileptic agents. The other emerging therapies include hypothermia, steroids, immunosuppressive agents, electrical and magnetic stimulation therapies, emergent respective epilepsy surgery, the ketogenic diet, pyridoxine infusion, cerebrospinal fluid drainage, and magnesium infusion. To date, there is a lack of robust published data regarding the safety and effectiveness of various therapies, and there continues to be a need for large randomized multicenter trials comparing newer therapies to treat this refractory condition.
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Affiliation(s)
- Batool F Kirmani
- 1Texas A&M University College of Medicine, College Station, TX, USA.,3Epilepsy and Functional Neurosurgery Program, Department of Neurology, CHI St. Joseph Health, Bryan, TX, USA
| | - Katherine Au
- 2George Washington University, School of Medicine & Health Sciences, Washington DC, USA
| | - Lena Ayari
- 1Texas A&M University College of Medicine, College Station, TX, USA
| | - Marita John
- 1Texas A&M University College of Medicine, College Station, TX, USA
| | - Padmashri Shetty
- 4M. S. Ramaiah Medical College, M. S. Ramaiah Nagar, Bengaluru, Karnataka, India
| | - Robert J Delorenzo
- 5Department of Neurology, Virginia Commonwealth University School of Medicine, Richmond, VA
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14
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Ziobro JM, Eschbach K, Shellhaas RA. Novel Therapeutics for Neonatal Seizures. Neurotherapeutics 2021; 18:1564-1581. [PMID: 34386906 PMCID: PMC8608938 DOI: 10.1007/s13311-021-01085-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2021] [Indexed: 02/04/2023] Open
Abstract
Neonatal seizures are a common neurologic emergency for which therapies have not significantly changed in decades. Improvements in diagnosis and pathophysiologic understanding of the distinct features of acute symptomatic seizures and neonatal-onset epilepsies present exceptional opportunities for development of precision therapies with potential to improve outcomes. Herein, we discuss the pathophysiology of neonatal seizures and review the evidence for currently available treatment. We present emerging therapies in clinical and preclinical development for the treatment of acute symptomatic neonatal seizures. Lastly, we discuss the role of precision therapies for genetic neonatal-onset epilepsies and address barriers and goals for developing new therapies for clinical care.
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Affiliation(s)
- Julie M Ziobro
- Department of Pediatrics, Michigan Medicine, C.S. Mott Children's Hospital, University of Michigan, 1540 E. Hospital Dr, Ann Arbor, MI, USA.
| | - Krista Eschbach
- Department of Pediatrics, Section of Neurology, Denver Anschutz School of Medicine, Children's Hospital Colorado, University of Colorado, Aurora, CO, 80045, USA
| | - Renée A Shellhaas
- Department of Pediatrics, Michigan Medicine, C.S. Mott Children's Hospital, University of Michigan, 1540 E. Hospital Dr, Ann Arbor, MI, USA
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15
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Falsaperla R, Scalia B, Giugno A, Pavone P, Motta M, Caccamo M, Ruggieri M. Treating the symptom or treating the disease in neonatal seizures: a systematic review of the literature. Ital J Pediatr 2021; 47:85. [PMID: 33827647 PMCID: PMC8028713 DOI: 10.1186/s13052-021-01027-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 03/15/2021] [Indexed: 01/08/2023] Open
Abstract
Aim The existing treatment options for neonatal seizures have expanded over the last few decades, but no consensus has been reached regarding the optimal therapeutic protocols. We systematically reviewed the available literature examining neonatal seizure treatments to clarify which drugs are the most effective for the treatment of specific neurologic disorders in newborns. Method We reviewed all available, published, literature, identified using PubMed (published between August 1949 and November 2020), that focused on the pharmacological treatment of electroencephalogram (EEG)-confirmed neonatal seizures. Results Our search identified 427 articles, of which 67 were included in this review. Current knowledge allowed us to highlight the good clinical and electrographic responses of genetic early-onset epilepsies to sodium channel blockers and the overall good response to levetiracetam, whose administration has also been demonstrated to be safe in both full-term and preterm newborns. Interpretation Our work contributes by confirming the limited availability of evidence that can be used to guide the use of anticonvulsants to treat newborns in clinical practice and examining the efficacy and potentially harmful side effects of currently available drugs when used to treat the developing newborn brain; therefore, our work might also serve as a clinical reference for future studies.
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Affiliation(s)
- Raffaele Falsaperla
- Neonatal Intensive Care Unit, A.O.U. San Marco-Policlinico, University of Catania, Via Carlo Azeglio Ciampi, 95121, Catania, Italy
| | - Bruna Scalia
- Neonatal Intensive Care Unit, A.O.U. San Marco-Policlinico, University of Catania, Via Carlo Azeglio Ciampi, 95121, Catania, Italy.
| | - Andrea Giugno
- Post graduate programme in Pediatrics, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Piero Pavone
- Unit of Clinical Pediatrics, A.O.U. "Policlinico", P.O. "G. Rodolico", University of Catania, Catania, Italy
| | - Milena Motta
- Neonatal Intensive Care Unit, A.O.U. San Marco-Policlinico, University of Catania, Via Carlo Azeglio Ciampi, 95121, Catania, Italy
| | - Martina Caccamo
- Neonatal Intensive Care Unit, A.O.U. San Marco-Policlinico, University of Catania, Via Carlo Azeglio Ciampi, 95121, Catania, Italy
| | - Martino Ruggieri
- Department of Clinical and Experimental Medicine Section of Pediatrics and Child Neuropsychiatry, A.O.U. San Marco- Policlinico, University of Catania, Catania, Italy
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16
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Abstract
Seizures are the most common neurological emergency in the neonates, and this age group has the highest incidence of seizures compared with any other period of life. The author provides a narrative review of recent advances in the genetics of neonatal epilepsies, new neonatal seizure classification system, diagnostics, and treatment of neonatal seizures based on a comprehensive literature review (MEDLINE using PubMED and OvidSP vendors with appropriate keywords to incorporate recent evidence), personal practice, and experience. Knowledge regarding various systemic and postzygotic genetic mutations responsible for neonatal epilepsy has been exploded in recent times, as well as better delineation of clinical phenotypes associated with rare neonatal epilepsies. An International League Against Epilepsy task force on neonatal seizure has proposed a new neonatal seizure classification system and also evaluated the specificity of semiological features related to particular etiology. Although continuous video electroencephalogram (EEG) is the gold standard for monitoring neonatal seizures, amplitude-integrated EEGs have gained significant popularity in resource-limited settings. There is tremendous progress in the automated seizure detection algorithm, including the availability of a fully convolutional neural network using artificial machine learning (deep learning). There is a substantial need for ongoing research and clinical trials to understand optimal medication selection (first line, second line, and third line) for neonatal seizures, treatment duration of antiepileptic drugs after cessation of seizures, and strategies to improve neuromorbidities such as cerebral palsy, epilepsy, and developmental impairments. Although in recent times, levetiracetam use has been significantly increased for neonatal seizures, a multicenter, randomized, blinded, controlled phase IIb trial confirmed the superiority of phenobarbital over levetiracetam in the acute suppression of neonatal seizures. While there is no single best choice available for the management of neonatal seizures, institutional guidelines should be formed based on a consensus of local experts to mitigate wide variability in the treatment and to facilitate early diagnosis and treatment.
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Affiliation(s)
- Debopam Samanta
- Child Neurology Section, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
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17
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Pollock S, Manganas LN. Use of levetiracetam in neonates. DIAGNOSIS, MANAGEMENT AND MODELING OF NEURODEVELOPMENTAL DISORDERS 2021:389-394. [DOI: 10.1016/b978-0-12-817988-8.00034-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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18
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Evaluation of the efficacy and safety of levetiracetam treatment for neonatal seizures in extremely preterm infants. JOURNAL OF SURGERY AND MEDICINE 2020. [DOI: 10.28982/josam.724986] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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19
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Karaoğlu P, Hız S, İşcan B, Polat AI, Ayanoğlu M, Duman N, Yiş' U. Intravenous Levetiracetam for Treatment of Seizures in Term and Preterm Neonates. J Pediatr Neurosci 2020; 15:15-20. [PMID: 32435300 PMCID: PMC7227750 DOI: 10.4103/jpn.jpn_66_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 11/18/2019] [Indexed: 01/15/2023] Open
Abstract
Context: Seizures are the most frequent neurological disturbance in the neonatal period, and there are no evidence-based guidelines for the treatment of neonatal seizures. Here we report a study on the use of levetiracetam as second-line therapy in the treatment of seizures in term and preterm neonates. Aim: The aim of this study was to assess the efficacy and safety of levetiracetam for seizures of term and preterm neonates. Settings and Design: We retrospectively analyzed data of the patients who had seizures and who were treated with levetiracetam as an add-on therapy to phenobarbital during the neonatal period. Statistical Analysis: The Statistical Package for the Social Sciences (SPSS) software, version 15.0 (SPSS, Chicago, Illinois), was used for statistical analysis. Continuous variables were expressed as mean values and standard deviations. Results: Thirty-six patients (8 term and 28 preterm) received levetiracetam. Mean dose of levetiracetam was 31.67 ± 14.83mg/kg/day. Twenty-five of the patients (69.4%) were seizure free with levetiracetam treatment. Electroencephalography recordings improved in 28 (77.8%) of the patients after levetiracetam. No severe adverse effects were observed. Conclusion: Our data suggest that levetiracetam may be a safe and effective treatment for neonatal seizures, which are unresponsive to phenobarbital.
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Affiliation(s)
- Pakize Karaoğlu
- Department of Pediatric Neurology, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey
| | - Semra Hız
- Department of Pediatric Neurology, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey
| | - Burçin İşcan
- Department of Neonatology, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey
| | - Ayşe I Polat
- Department of Pediatric Neurology, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey
| | - Müge Ayanoğlu
- Department of Pediatric Neurology, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey
| | - Nuray Duman
- Department of Neonatology, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey
| | - Uluç Yiş'
- Department of Pediatric Neurology, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey
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20
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Thibault C, Naim MY, Abend NS, Licht DJ, Gaynor JW, Xiao R, Massey SL. A retrospective comparison of phenobarbital and levetiracetam for the treatment of seizures following cardiac surgery in neonates. Epilepsia 2020; 61:627-635. [PMID: 32162678 DOI: 10.1111/epi.16469] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 02/07/2020] [Accepted: 02/13/2020] [Indexed: 01/10/2023]
Abstract
OBJECTIVE To compare the safety and efficacy of phenobarbital and levetiracetam in a cohort of neonates with seizures following cardiac surgery. METHODS We performed a retrospective single-center study of consecutive neonates with electrographically confirmed seizures managed with antiseizure medication after cardiac surgery from June 15, 2012 to December 31, 2018. We compared the safety and efficacy of phenobarbital and levetiracetam as first-line therapy. RESULTS First-line therapy was phenobarbital in 31 neonates and levetiracetam in 22 neonates. Phenobarbital was associated with more adverse events (P = .006). Eight neonates (14%) experienced an adverse event related to phenobarbital use, including seven with hypotension and one with respiratory depression. No adverse events were reported with levetiracetam use. The cessation of electrographic seizures was similar in both groups, including 18 neonates (58%) with seizure cessation after phenobarbital and 12 neonates (55%) with seizure cessation after levetiracetam (P = 1.0). The combined cessation rates of phenobarbital and levetiracetam when used as first- or second-line therapy were 58% and 47%, respectively (P = .47). SIGNIFICANCE Phenobarbital was associated with more adverse events than levetiracetam, and the two drugs were equally but incompletely effective in treating electrographically confirmed seizures in neonates following cardiac surgery. Given its more acceptable safety profile and potential noninferiority, levetiracetam may be a reasonable option for first-line therapy for treatment of seizures in this population. Further prospective studies are needed to confirm these results.
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Affiliation(s)
- Céline Thibault
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Maryam Y Naim
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Nicholas S Abend
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.,Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Daniel J Licht
- Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania
| | - J William Gaynor
- Division of Cardiothoracic Surgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Rui Xiao
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
| | - Shavonne L Massey
- Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania
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21
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Lack of response to treatment with levetiracetam in extreme preterm infants with seizures. J Perinatol 2019; 39:1480-1484. [PMID: 31548579 DOI: 10.1038/s41372-019-0498-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 07/25/2019] [Accepted: 08/01/2019] [Indexed: 01/05/2023]
Abstract
OBJECTIVE The aim of this study was to evaluate the effectiveness of monotherapy with levetiracetam (LEV) in achieving seizure cessation in a retrospective cohort of extreme preterm infants with seizures. STUDY DESIGN Charts of infants with a diagnosis of neonatal seizures admitted to the NICU between 2013 and 2017 were reviewed. Seizures were diagnosed using continuous video electroencephalography. All infants were initially started on LEV and reached a dose of 80 mg/kg/day. Other ASMs were added to LEV if seizures continued after 2 days. Data on additional clinical variables were collected for each infant. RESULT Sixty-one infants born <28 weeks of gestation met inclusion criteria. Seventy-four percent of patients did not respond to LEV monotherapy and required additional medications. CONCLUSIONS LEV monotherapy stopped seizures in only a small portion of cases.
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22
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Ghosh S, Miskimen ACC, Brady J, Robinson MA, Zou B, Weiss M, Kang PB. Neurodevelopmental outcomes at 9-14 months gestational age after treatment of neonatal seizures due to brain injury. Childs Nerv Syst 2019; 35:1571-1578. [PMID: 31278442 PMCID: PMC6959470 DOI: 10.1007/s00381-019-04286-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 06/30/2019] [Indexed: 02/06/2023]
Abstract
PURPOSE Infants with brain injury are susceptible to developmental delays. Survivors of neonatal seizures are at risk for developmental delay, epilepsy, and further neurological comorbidities. Despite advances in neonatal critical care, the prevalence of adverse long-term outcomes and seizure recurrence remains unchanged. Our goal is to determine if early treatment of neonatal seizures with phenobarbital or levetiracetam is associated with worse neurodevelopmental outcomes in brain-injured infants. METHODS We conducted a retrospective cohort study of 119 infants admitted between 2013 and 2017 who were at risk for developmental delay and assessed in our clinic. We compared brain injury infants with neonatal seizures to brain injury infants without neonatal seizures using Bayley scores (BSID III) at 9-14 months gestational age. A comparison of Bayley scores between those exposed to phenobarbital and levetiracetam was conducted. RESULTS Twenty-two children with neonatal seizures scored lower than 53 children without seizures in all domains with significant values in composite scores for cognitive function (p = 0.003) and language (p = 0.031). We found no difference in scores at 9-14 months between infants exposed to phenobarbital versus levetiracetam. CONCLUSIONS Our results suggest that in infants with brain injury, the occurrence of neonatal seizures has an adverse effect on neurodevelopmental outcomes. The choice of antiseizure medication may not play a significant role in their outcomes.
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Affiliation(s)
- Suman Ghosh
- Division of Pediatric Neurology, Department of Pediatrics, University of Florida College of Medicine, 1600 SW Archer Rd, Gainesville, FL, 32610, USA.
| | - Andrea C Cabassa Miskimen
- College of Liberal Arts and Sciences at the University of Florida, College of Medicine, Gainesville, FL
| | - Janet Brady
- University of Florida Rehabilitation for Kids, Gainesville, FL
| | - Matthew A Robinson
- Department of Biostatistics, University of Florida College of Medicine, Gainesville, FL
| | - Baiming Zou
- Department of Biostatistics, University of Florida College of Medicine, Gainesville, FL
| | - Michael Weiss
- Division of Neonatology at University of Florida College of Medicine, Gainesville, FL
| | - Peter B. Kang
- Division of Pediatric Neurology, University of Florida College of Medicine, Gainesville, FL
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23
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Kreimer AM, Littrell RA, Gibson JB, Leung NR. Effectiveness of Levetiracetam as a First-Line Anticonvulsant for Neonatal Seizures. J Pediatr Pharmacol Ther 2019; 24:320-326. [PMID: 31337995 DOI: 10.5863/1551-6776-24.4.320] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Optimal treatment for neonatal seizures remains unclear, and management among US hospitals is highly varied. The purpose of this study was to evaluate the effectiveness of levetiracetam as a first-line treatment for seizures in a neonatal population. METHODS A single-center, retrospective review of neonates at a tertiary medical center who received levetiracetam as a first-line agent after benzodiazepines for seizure control between 2015 and 2017 was conducted. Chart review was completed to analyze patient and treatment characteristics. The primary outcome was seizure control, defined as clinical seizure cessation and video electroencephalogram resolution, with no new seizures documented prior to discharge. RESULTS A total of 36 patients met inclusion criteria. Seventeen patients (47%) had seizure control after intravenous levetiracetam as monotherapy. Eighteen patients required a second anticonvulsant, of which 13 (72%) had seizure control. In total, 30 patients (83%) had seizure control with levetiracetam monotherapy or combination therapy of levetiracetam plus fosphenytoin or phenobarbital. CONCLUSIONS Levetiracetam monotherapy provided seizure control in about 50% of the patients reviewed. Overall, seizure control was observed in 83% of the study population that received either levetiracetam monotherapy or combination therapy of levetiracetam plus fosphenytoin or phenobarbital as a second-line agent. Further studies are warranted to directly compare historical therapies with levetiracetam for neonatal seizure control.
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Wang M, Li W, Tao Y, Zhao L. Emerging trends and knowledge structure of epilepsy during pregnancy research for 2000-2018: a bibliometric analysis. PeerJ 2019; 7:e7115. [PMID: 31211023 PMCID: PMC6557303 DOI: 10.7717/peerj.7115] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 05/10/2019] [Indexed: 01/07/2023] Open
Abstract
Background Epilepsy during pregnancy presents a unique set of challenges for pregnant women, the fetus, and the health care community. As research in this area advances rapidly, it is critical to keep up with the emerging trends and key turning points of the development of the domain knowledge. This study aimed to construct a series of science maps to quantitatively and qualitatively evaluate the intellectual landscape and research frontiers in the field of epilepsy during pregnancy research. Methods All publications were extracted from the Web of Science Core Collection database. Bibliometric analysis was used to analyze the scientific research outputs, including journals, countries/regions, institutions, authors (cited authors), intellectual base and research hotspots. Results A total of 2,225 publications related to epilepsy during pregnancy were identified as published between 2000 and 2018. The overall trend of the number of publications showed a fluctuating growth from 59 articles in 2000 to 198 in 2018. Neurology was the leading journal in the field of epilepsy and pregnancy research both in terms of impact factor score (8.055) and H-index value (77). The US retained its leading position and exerted a pivotal influence in this area. The University of Melbourne was identified as a good research institution for research collaboration. Prof. Pennell and Tomson have made great achievements in this area, and Prof. Tomson laid a foundation for the development of this domain. The keyword “neonatal seizures” ranked first in research hotspots, and the keyword “autism spectrum disorders (ASD)” ranked first in research frontiers. Conclusions Epilepsy during pregnancy is a fascinating and rapid development of subject matter. A more recent emerging trend focused on comprehensive management of pregnant and lactating women, evaluation of the safety and efficacy of newer antiepileptic drugs. The keywords “management issue,” “brain injury,” “meta-analysis,” “in utero exposure,” and “ASD” were the latest research frontiers and should be closely observed.
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Affiliation(s)
- Minglu Wang
- Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Weitao Li
- Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Yuying Tao
- Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Limei Zhao
- Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
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Zavadenko AN, Medvedev MI, Degtyareva MG. [Assessment of neurodevelopment in children of different gestational age with neonatal seizures]. Zh Nevrol Psikhiatr Im S S Korsakova 2019; 118:35-42. [PMID: 30585602 DOI: 10.17116/jnevro201811811135] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
AIM To assess psychomotor development in infants with neonatal seizures (NS) born with different gestational age, by means of Bayley-III scales of infant and toddler development, in their corrected age of 1 year. MATERIAL AND METHODS The study included 52 infants, who had NS and were born with different gestational age: 28 weeks or less (n=26) - group I, 29-32 weeks (n=16) - group II, 33-36 weeks (n=3) - group III, 37-41 weeks (n=7) - group IV. The infants' neurodevelopment was evaluated in their corrected age of 1 year by means of N. Bayley scales of infant and toddler development, third edition: Cognitive, Language, Motor, Social-Emotional, and Adaptive Behavior. RESULTS AND CONCLUSION Only 17 (32,7%) of 52 examined infants did not demonstrate any developmental delay on each of five Bayley-III scales. Significant developmental delay (composite score <70) on at least one scale was revealed in 23 (44,2%) patients, including 12 (46,2%) in group I, 5 (31,3%) in group II, 6 (60%) of 10 in the combined group III-IV. In most cases, neurodevelopmental delays were attributed to only one domain and could be indicated as partial. The conclusion about global developmental retardation (the composite scores 55 or less on all five scales) was done in 3 patients, each of whom had a co-morbidity of cerebral palsy and epilepsy.
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Affiliation(s)
- A N Zavadenko
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - M I Medvedev
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - M G Degtyareva
- Pirogov Russian National Research Medical University, Moscow, Russia
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Short-Term Neurodevelopmental Outcome in Term Neonates Treated with Phenobarbital versus Levetiracetam: A Single-Center Experience. Behav Neurol 2019; 2019:3683548. [PMID: 31281546 PMCID: PMC6589264 DOI: 10.1155/2019/3683548] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Revised: 04/08/2019] [Accepted: 04/14/2019] [Indexed: 11/17/2022] Open
Abstract
Background Phenobarbital (PB) has been traditionally used as the first-line treatment for neonatal seizures. More recently, levetiracetam (LEV) has been increasingly used as a promising newer antiepileptic medication for treatment of seizures in neonates. Objectives The aim of our study was to compare the effect of PB vs. LEV on short-term neurodevelopmental outcome in infants treated for neonatal seizures. Method This randomized, one-blind prospective study was conducted on term neonates admitted to the Neonatal Intensive Care Unit of S. Bambino Hospital, University Hospital "Policlinico-Vittorio Emanuele," Catania, Italy, from February 2016 to February 2018. Thirty term neonates with seizures were randomized to receive PB or LEV; the Hammersmith Neonatal Neurological Examination (HNNE) was used at baseline (T0) and again one month after the initial treatment (T1). Results We found a significantly positive HNNE score for the developmental outcomes, specifically tone and posture, in neonates treated with LEV. There was no significant improvement in the HNNE score at T1 in the neonates treated with PB. Conclusion This study suggests a positive effect of levetiracetam on tone and posture in term newborns treated for neonatal seizures. If future randomized-controlled studies also show better efficacy of LEV in the treatment of neonatal seizures, LEV might potentially be considered as the first-line anticonvulsant in this age group.
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Ahrens S, Ream MA, Slaughter LA. Status Epilepticus in the Neonate: Updates in Treatment Strategies. Curr Treat Options Neurol 2019; 21:8. [PMID: 30773607 DOI: 10.1007/s11940-019-0546-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW The purpose of this review is to report recent advances in treatment of neonatal seizures, with a specific focus on new literature since a 2013 systematic review performed by this author (Slaughter) and others. There is a paucity of data with regard to well-defined status epilepticus (SE) in neonates, so treatment of recurrent seizures was also included in this inquiry. We aimed to summarize the efficacy and safety profiles of current therapeutic options as well as describe trends in medication selection in the neonatal intensive care unit (NICU) setting. RECENT FINDINGS Phenobarbital remains first-line therapy in practice, though there is increasing evidence of its neurotoxicity and long-term sequelae. Bumetanide failed an open-label trial for efficacy, demonstrated an increased risk for hearing loss, and has since fallen out of favor for use in this population. New agents, such as levetiracetam and topiramate, still have very limited data but appear to be as efficacious as older medications, with more favorable side effect profiles. There are limited high-level evidence-based data to guide treatment of neonatal seizures. Emerging research focusing on drug mechanisms and safety profiles may provide additional information to guide decisions; however, further research is needed.
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Affiliation(s)
- Stephanie Ahrens
- Division of Neurology, Department of Pediatrics, Nationwide Children's Hospital, Ohio State University, 611 E Livingston Avenue FB4, Columbus, OH, 43205, USA.
| | - Margie A Ream
- Division of Neurology, Department of Pediatrics, Nationwide Children's Hospital, Ohio State University, 611 E Livingston Avenue FB4, Columbus, OH, 43205, USA
| | - Laurel A Slaughter
- Division of Neurology, Department of Pediatrics, Nationwide Children's Hospital, Ohio State University, 611 E Livingston Avenue FB4, Columbus, OH, 43205, USA
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Favrais G, Ursino M, Mouchel C, Boivin E, Jullien V, Zohar S, Saliba E. Levetiracetam optimal dose-finding as first-line treatment for neonatal seizures occurring in the context of hypoxic-ischaemic encephalopathy (LEVNEONAT-1): study protocol of a phase II trial. BMJ Open 2019; 9:e022739. [PMID: 30679288 PMCID: PMC6347888 DOI: 10.1136/bmjopen-2018-022739] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Therapeutic schedules for treating neonatal seizures remain elusive. First-line treatment with phenobarbital is widely supported but without strong scientific evidence. Levetiracetam (LEV) is an emerging and promising antiepileptic drug (AED). The aim of this phase II trial is to determine the benefits of LEV by applying a strict methodology and to estimate the optimal dose of LEV as a first-line AED to treat seizures in newborns suffering from hypoxic-ischaemic encephalopathy. METHODS AND ANALYSIS LEVNEONAT-1 is an open and sequential LEV dose-finding study. The optimal dose is that which is estimated to be associated with a toxicity not exceeding 10% and an efficacy higher than 60%. Efficacy is defined by a seizure burden reduction of 80% after the loading dose. Four increasing dose regimens will be assessed including one loading dose of 30, 40, 50 or 60 mg/kg followed by eight maintenance doses (ie, a quarter of the loading dose) injected every 8 hours. A two-patient cohort will be necessary at each dose level to consider an upper dose level assignment. The maximal sample size expected is 50 participants with a minimum of 24 patients or fewer in the case of a high rate of toxicity. Patients will be recruited in five neonatal intensive care units beginning in October 2017 and continuing for 2 years. In parallel, the LEV pharmacokinetics will be measured five times (ie, 30 min; 4 and 7 hours after the loading dose; 1-3 hours and 12-18 hours after the last maintenance dose). ETHICS AND DISSEMINATION Ethics approval has been obtained from the regional ethical committee (2016-R25) and the French Drug Safety Agency (160652A-31). The results will be published in a peer-reviewed journal. The results will also be presented at medical meetings. TRIAL REGISTRATION NUMBER NCT02229123; Pre-results.
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Affiliation(s)
- Geraldine Favrais
- Neonatal Intensive Care Unit, CHRU de Tours, Tours, France
- UMR 1253, iBrain, Université de Tours, INSERM, Tours, France
| | - Moreno Ursino
- INSERM, UMRS 1138, team 22, CRC, Université Paris 5, Université Paris 6, Paris, France
| | - Catherine Mouchel
- INSERM CIC-1414, Clinical investigation Center, Université Rennes 1, Rennes, France
- Department of Clinical Pharmacology, CHRU de Rennes, Rennes, France
| | - Estelle Boivin
- Research Clinical and Innovation Delegation, CHRU de Tours, Tours, France
| | - Vincent Jullien
- INSERM U1129, Department of Pharmacology, Université Paris Descartes, Hôpital Européen Georges Pompidou, Paris, France
| | - Sarah Zohar
- INSERM, UMRS 1138, team 22, CRC, Université Paris 5, Université Paris 6, Paris, France
| | - Elie Saliba
- Neonatal Intensive Care Unit, CHRU de Tours, Tours, France
- UMR 1253, iBrain, Université de Tours, INSERM, Tours, France
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Rao LM, Hussain SA, Zaki T, Cho A, Chanlaw T, Garg M, Sankar R. A comparison of levetiracetam and phenobarbital for the treatment of neonatal seizures associated with hypoxic-ischemic encephalopathy. Epilepsy Behav 2018; 88:212-217. [PMID: 30296665 DOI: 10.1016/j.yebeh.2018.09.015] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 08/17/2018] [Accepted: 09/16/2018] [Indexed: 01/29/2023]
Abstract
PURPOSE Seizures are common in term infants with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia. Although phenobarbital (PHB) is generally considered first-line therapy, some centers have embraced third-generation antiepileptic drugs (AEDs) such as levetiracetam (LEV) given the impression of comparable efficacy and superior tolerability. We set out to compare the efficacy of PHB and LEV in a large single-center cohort. METHODS We retrospectively identified consecutive newborns with HIE who were monitored with continuous video-electroencephalogram (VEEG) for the duration of therapeutic hypothermia. After identification of seizures, infants were treated with PHB or LEV at the discretion of treating physicians. We assessed time to seizure freedom as a function of AED choice, with adjustment for HIE severity and initial seizure frequency using the Kaplan-Meier procedure and multivariate Cox proportional hazards regression. RESULTS We identified 78 infants with HIE. Among 44 (56%) patients who had VEEG-confirmed seizures, 34 became seizure-free during monitoring, and the remaining 10 died. Initial treatment with LEV, in comparison with PHB, predicted a shorter interval to seizure freedom in a univariate analysis (Hazard ratio (HR) = 2.58, P = 0.007), even after adjustment for initial seizure frequency and an unbiased ad hoc measure of HIE severity (adjusted HR = 2.57, P = 0.010). This effect was recapitulated in an analysis in which patients with treatment crossover were excluded. As expected, severity of HIE was an independent predictor of longer duration to seizure freedom (HR = 0.16, P < 0.001) and remained a significant predictor after adjustment for initial seizure burden and treatment agent. CONCLUSION Despite a relatively small sample size and retrospective design, this study suggests that LEV is a viable alternative to PHB in the treatment of neonatal seizures associated with HIE. A large-scale randomized controlled trial is needed to confirm these findings.
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Affiliation(s)
- Lekha M Rao
- Division of Neurology, Department of Pediatrics, UCLA Mattel Children's Hospital, USA
| | - Shaun A Hussain
- Division of Neurology, Department of Pediatrics, UCLA Mattel Children's Hospital, USA.
| | - Timothy Zaki
- Division of Neurology, Department of Pediatrics, UCLA Mattel Children's Hospital, USA
| | - Alexander Cho
- School of Medicine and Health Sciences, George Washington University, USA
| | - Teresa Chanlaw
- Division of Neonatology, Department of Pediatrics, UCLA Mattel Children's Hospital, USA
| | - Meena Garg
- Division of Neonatology, Department of Pediatrics, UCLA Mattel Children's Hospital, USA
| | - Raman Sankar
- Division of Neurology, Department of Pediatrics, UCLA Mattel Children's Hospital, USA; Department of Neurology, David Geffen School of Medicine at UCLA, USA
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Spagnoli C, Falsaperla R, Deolmi M, Corsello G, Pisani F. Symptomatic seizures in preterm newborns: a review on clinical features and prognosis. Ital J Pediatr 2018; 44:115. [PMID: 30382869 PMCID: PMC6211591 DOI: 10.1186/s13052-018-0573-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 10/16/2018] [Indexed: 01/23/2023] Open
Abstract
Neonatal seizures are the most common neurological event in newborns, showing higher prevalence in preterm than in full-term infants. In the majority of cases they represent acute symptomatic phenomena, the main etiologies being intraventricular haemorrhage, hypoxic-ischemic encephalopathy, central nervous system infections and transient metabolic derangements.Current definition of neonatal seizures requires detection of paroxysmal EEG-changes, and in preterm newborns the incidence of electrographic-only seizures seems to be particularly high, further stressing the crucial role of electroencephalogram monitoring in this population. Imaging work-up includes an integration of serial cranial ultrasound and brain magnetic resonance at term-equivalent age. Unfavourable outcomes following seizures in preterm infants include death, neurodevelopmental impairment, epilepsy, cerebral palsy, hearing and visual impairment. As experimental evidence suggests a detrimental role of seizures per se in determining subsequent outcome, they should be promptly treated with the aim to reduce seizure burden and long-term disabilities. However, neonatal seizures show low response to conventional anticonvulsant drugs, and this is even more evident in preterm newborns, due to intrinsic developmental factors. As a consequence, as literature does not provide any specific guidelines, due to the lack of robust evidence, off-label medications are often administered in clinical practice.
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Affiliation(s)
- Carlotta Spagnoli
- Child Neuropsychiatry Unit, Department of Pediatrics, Arcispedale Santa Maria Nuova, IRCSS, Reggio Emilia, Italy
| | - Raffaele Falsaperla
- Neonatal Intensive Care Unit, Santo Bambino Hospital, University Hospital "Policlinico-Vittorio Emanuele", Via Tindaro 2, 95124, Catania, Italy.
| | - Michela Deolmi
- Pediatrics Unit, Medicine & Surgery Department, University of Parma, Parma, Italy
| | - Giovanni Corsello
- Department of Maternal and Child Health, University of Palermo, Palermo, Italy
| | - Francesco Pisani
- Child Neuropsychiatry Unit, Medicine & Surgery Department, Neuroscience Division, University of Parma, Parma, Italy
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Han JY, Moon CJ, Youn YA, Sung IK, Lee IG. Efficacy of levetiracetam for neonatal seizures in preterm infants. BMC Pediatr 2018; 18:131. [PMID: 29636029 PMCID: PMC5892045 DOI: 10.1186/s12887-018-1103-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Accepted: 03/27/2018] [Indexed: 11/13/2022] Open
Abstract
Background Neonatal seizures remain a significant clinical problem, and therapeutic options are still not diverse with limited efficacy. Levetiracetam (LEV) is a relatively new and wide spectrum anti-seizure medication with favorable pharmacokinetics and safety profile. In the recent decades, LEV has been increasingly used for the treatment of neonatal seizures. The aim of this study was to describe the experience of using LEV as the first line anti-seizure medication for preterm infants. Methods A retrospective analysis of 37 preterm infants who were treated with LEV as the first-line anti-seizure medication was performed. Results Mean gestational age of the 37 preterm infants was 31.5 ± 1.9 weeks (range, 26 to 36+ 6 weeks). Twenty-one infants (57%) were seizure-free while given LEV at the end of the first week, and no additional anti-seizure medication was required. Loading doses of LEV ranged from 40 to 60 mg/kg (mean 56 mg/kg) and the maintenance dose ranged from 20 to 30 mg/kg (mean 23 mg/kg). No adverse effect was observed. Conclusions Levetiracetam can be a good and safe choice for treatment of neonatal seizures in preterm infants. Prospective double blind controlled studies are needed in the future.
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Affiliation(s)
- Ji Yoon Han
- Department of Pediatrics, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpodaero, Seochogu, Seoul, 137-701, South Korea
| | - Chung Joon Moon
- Department of Pediatrics, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpodaero, Seochogu, Seoul, 137-701, South Korea
| | - Young Ah Youn
- Department of Pediatrics, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpodaero, Seochogu, Seoul, 137-701, South Korea
| | - In Kyung Sung
- Department of Pediatrics, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpodaero, Seochogu, Seoul, 137-701, South Korea
| | - In Goo Lee
- Department of Pediatrics, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpodaero, Seochogu, Seoul, 137-701, South Korea.
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Natarajan N, Beatty CW, Gust J, Hamiwka L. Provider Practices of Phenobarbital Discontinuation in Neonatal Seizures. J Child Neurol 2018; 33:153-157. [PMID: 29256315 DOI: 10.1177/0883073817745990] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Neonatal seizures are treated with phenobarbital and prolonged treatment does not prevent postneonatal epilepsy. The authors documented factors influencing phenobarbital use and determined whether published data changed practice. A total of 83 neonates with symptomatic seizures, clinical or electrographic, were evaluated for treatment, incidence of postneonatal epilepsy, and associated factors. Median phenobarbital treatment was 81 days. Nineteen children (23%) developed postneonatal epilepsy. Longer duration of seizures and an infectious etiology were associated with postneonatal epilepsy suggesting no impact on duration of phenobarbital treatment. Treatment duration was associated with duration of seizures and use of a second antiseizure medication. This study supports early discontinuation of phenobarbital and suggests providers utilize factors such as use of a second antiseizure medication and time to seizure control to determine phenobarbital duration, despite prior studies suggesting no impact of treatment length.
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Affiliation(s)
- Niranjana Natarajan
- 1 Department of Neurology, Division of Pediatric Neurology, University of Washington, Seattle Children's Hospital, Seattle, WA, USA
| | - Christopher W Beatty
- 1 Department of Neurology, Division of Pediatric Neurology, University of Washington, Seattle Children's Hospital, Seattle, WA, USA
| | - Juliane Gust
- 1 Department of Neurology, Division of Pediatric Neurology, University of Washington, Seattle Children's Hospital, Seattle, WA, USA
| | - Lorie Hamiwka
- 1 Department of Neurology, Division of Pediatric Neurology, University of Washington, Seattle Children's Hospital, Seattle, WA, USA
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Yozawitz E, Stacey A, Pressler RM. Pharmacotherapy for Seizures in Neonates with Hypoxic Ischemic Encephalopathy. Paediatr Drugs 2017; 19:553-567. [PMID: 28770451 DOI: 10.1007/s40272-017-0250-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Seizures are common in neonates with moderate and severe hypoxic ischemic encephalopathy (HIE) and are associated with worse outcomes, independent of HIE severity. In contrast to adults and older children, no new drugs have been licensed for treatment of neonatal seizures over the last 50 years, because of a lack of controlled clinical trials. Hence, many antiseizure medications licensed in older children and adults are used off-label for neonatal seizure, which is associated with potential risks of adverse effects during a period when the brain is particularly vulnerable. Phenobarbital is worldwide the first-line drug and is considered standard of care, although there is a limited evidence base for its efficacy. Second-line agents include phenytoin, benzodiazepines, levetiracetam, and lidocaine. These drugs are discussed in more detail along with two emerging drugs (bumetanide and topiramate). More safety, pharmacokinetic, and efficacy data are needed from well-designed clinical trials to develop safe and effective antiseizure regimes for the treatment of neonatal seizures in HIE.
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Affiliation(s)
- Elissa Yozawitz
- Department of Neurology and Pediatrics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Arthur Stacey
- UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK
| | - Ronit M Pressler
- Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, Great Ormond Street, London, WC1N 3JH, UK. .,Clinical Neurosciences, UCL- Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
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Abstract
Neonatal seizures constitute the most frequent presenting neurologic sign encountered in the neonatal intensive care unit. Despite limited efficacy and safety data, phenobarbital continues to be used near-universally as the first-line anti-seizure drug (ASD) in neonates. The choice of second-line ASDs varies by provider and institution, and is still not supported by sufficient scientific evidence. In this review, we discuss the available evidence supporting the efficacy, mechanism of action, potential adverse effects, key pharmacokinetic characteristics such as interaction with therapeutic hypothermia, logistical issues, and rationale for use of neonatal ASDs. We describe the widely used neonatal ASDs, namely phenobarbital, phenytoin, midazolam, and levetiracetam, in addition to potential ASDs, including lidocaine, topiramate, and bumetanide.
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Affiliation(s)
- Mohamed El-Dib
- Neonatal Neurocritical Care, Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
| | - Janet S Soul
- Fetal-Neonatal Neurology Program, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
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Sedighi M, Asadi F, Moradian N, Vakiliamini M, Moradian M. Efficacy and safety of levetiracetam in the management of seizures in neonates. ACTA ACUST UNITED AC 2017; 21:232-5. [PMID: 27356654 PMCID: PMC5107289 DOI: 10.17712/nsj.2016.3.20150726] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To evaluate the efficacy and safety of levetiracetam (LEV) in the management of seizures in neonates. METHODS A prospective non-blind, single arm clinical trial conducted in the Department of Neonatology and Pediatric Intensive Care, Mohamad Kermanshahi, and Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran from May 2014 to December 2014. Fifty out of 60 newborns with gestational age >/=30 weeks with clinically diagnosed seizures were included. Levetiracetam was administered orally with an initial dose of 10 mg/kg twice a day. The patients were observed continuously by Neuro Intensive Care nurses, and visited daily by a neuropediatrician in the first 7 days and then at days 14, 30, and 90 after the start of LEV administration. Clinical examination was performed for every patient, and seizure number, antiepileptic medication, and adverse events were detailed at every visit. RESULTS 47 infants were seizure free under LEV at the end of the first week, 47 remained seizure free at 4 weeks, and 46 remained seizure free at 11 weeks. No immediate and long-term side effects were noted in our patients. CONCLUSION This study investigated the efficacy and safety of LEV in neonatal seizure control but confirmation with further randomized controlled trials is required.
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Affiliation(s)
- Mostafa Sedighi
- Department of Neurology, Mohamad Kermanshahi Hospital, Kermanshah, Islamic Republic of Iran
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Lloreda-García JM, Fernández-Fructuoso JR, Gómez-Santos E, García-González A, Leante-Castellanos JL. Uso de levetiracetam en crisis convulsivas neonatales. An Pediatr (Barc) 2017; 86:286-288. [DOI: 10.1016/j.anpedi.2016.08.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 07/26/2016] [Accepted: 08/01/2016] [Indexed: 10/20/2022] Open
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Use of levetiracetam in neonatal seizures. ANALES DE PEDIATRÍA (ENGLISH EDITION) 2017. [DOI: 10.1016/j.anpede.2016.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Changing antiepileptic drug use for seizures in US neonatal intensive care units from 2005 to 2014. J Perinatol 2017; 37:296-300. [PMID: 27831551 DOI: 10.1038/jp.2016.206] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2016] [Revised: 09/17/2016] [Accepted: 10/07/2016] [Indexed: 01/18/2023]
Abstract
OBJECTIVE Neonatal seizures are a common problem in the neonatal intensive care unit and are frequently treated with antiepileptic drugs. Limited data exist on current or changing antiepileptic drug use for seizures in the neonatal intensive care unit.We sought to describe trends of antiepileptic drug exposure in a large volume of US neonatal intensive care unit from 2005 to 2014 and we hypothesized increasing levetiracetam exposure over the 10-year study period. STUDY DESIGN Retrospective cohort study of infants from the Pediatrix Medical Group Clinical Data Warehouse, a large, multicenter, deidentified data set. Data were analyzed for trends in 2-year time periods. Our cohort included infants with a diagnosis of seizures who received an antiepileptic drug that were discharged from the neonatal intensive care unit from 1 January 2005 to 31 December 2014. RESULTS Among 778 395 infants from 341 facilities, we identified 9134 infants with a seizure diagnosis who received an antiepileptic drug. Phenobarbital was used in 98% of the cohort. From 2005-2006 to 2013-2014 phenobarbital exposure declined from 99 to 96% (P<0.001), phenytoin exposure decreased from 15 to 11% (P<0.001) and levetiracetam exposure increased 10-fold from 1.4 to 14% (P<0.001). Overall, <1% of infants were exposed to carbamazepine, lidocaine or topiramate. CONCLUSIONS Infants with seizures were overwhelmingly exposed to phenobarbital, despite a significant increase in levetiracetam exposure. The use of phenytoin declined and has been surpassed by levetiracetam as the second most widely used antiepileptic in the neonatal intensive care unit. These changes in antiepileptic drug usage patterns have occurred in the absence of novel efficacy data in neonates.
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Shin JW, Jung YS, Park K, Lee SM, Eun HS, Park MS, Park KI, Namgung R. Experience and pharmacokinetics of Levetiracetam in Korean neonates with neonatal seizures. KOREAN JOURNAL OF PEDIATRICS 2017; 60:50-54. [PMID: 28289434 PMCID: PMC5346509 DOI: 10.3345/kjp.2017.60.2.50] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Revised: 10/20/2016] [Accepted: 10/25/2016] [Indexed: 11/27/2022]
Abstract
Purpose The aims of this study were to evaluate the safety and pharmacokinetics of levetiracetam (LEV) in neonates with seizures and to establish a population pharmacokinetics (PPK) model by using the software NONMEM. Methods A retrospective analysis of 18 neonatal patients with seizures, who were treated with LEV, including 151 serum samples, was performed. The mean loading dose was 20 mg/kg, followed by a mean maintenance dose of 29 mg/kg/day. Results Seventeen neonates (94%) had seizure cessation within 1 week and 16 (84%) remained seizure-free at 30 days under the LEV therapy. The mean serum concentration of LEV was 8.7 µg/mL. Eight samples (5%) were found above the therapeutic range. No serious adverse effects were detected. In the PPK analysis for Korean neonates, the half-life was 9.6 hours; clearance, 0.357 L/hr; and volume of distribution, 4.947 L, showing differences from those in adults. Conclusion LEV is a safe and effective option for the treatment of neonatal seizures with careful therapeutic drug monitoring.
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Affiliation(s)
- Jae Won Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Yun Seob Jung
- Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea
| | - Kyungsoo Park
- Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea
| | - Soon Min Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Ho Seon Eun
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Min Soo Park
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Kook In Park
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Ran Namgung
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
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Yau MLY, Fung ELW, Ng PC. Response of levetiracetam in neonatal seizures. World J Clin Pediatr 2015; 4:45-49. [PMID: 26261766 PMCID: PMC4526838 DOI: 10.5409/wjcp.v4.i3.45] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Revised: 05/25/2015] [Accepted: 06/16/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To review the clinical response to levetiracetam (LEV) in neonatal seizure management in intensive care unit.
METHODS: Medical records of neonates who received LEV from January 2009 to August 2014 were reviewed. Their demographic data, clinical characteristics, etiology, seizures, electroencephalograms, response to treatment and outcome were noted. Literature review of use of LEV in neonates were also performed via PubMed and EMBASE with keywords - “neonates”, “seizures”, “epilepsy” and “LEV” up to Sep 2014 and retrieved the publications. The response rate to LEV was compared.
RESULTS: Twelve neonates were identified during the study period. All patients received phenobarbitone loading prior to consideration of LEV. Seven (58%) and nine (75%) achieved seizure freedom 24 h and 72 h after LEV was added, both clinically and electrographically. No serious adverse effects were associated with LEV use. From the literature, there are total 144 neonates reported to have used LEV. The overall results suggested that LEV could control up to 90% of neonatal seizures.
CONCLUSION: LEV was found to be relatively safe and efficacious in treating neonatal seizures, but might not work well in the most severe hypoxic ischemic encephalopathy.
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Abstract
Seizures are most often the only sign of a central nervous dysfunction in the neonate. Neonatal seizures are a symptom of a specific disease entity. The search for a cause of neonatal seizures should focus on perinatal history or acute metabolic changes in the neonate. There are four classifications of neonatal seizures: clonic, tonic, myoclonic, and subtle. Simultaneous electroencephalogram and video recording are tools to assist the practitioner in the evaluation of difficult-to-assess subtle behaviors. Although many seizures may be prevented by careful attention to metabolic changes and the neonate's overall condition, those that cannot be prevented may require pharmacologic treatment. First-generation antiepileptic drugs such as phenobarbital and phenytoin are still the first and second lines of therapy, even as questions concerning their limited clinical effectiveness and concern for potential neurotoxicity continue.
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MESH Headings
- Anticonvulsants/classification
- Anticonvulsants/pharmacology
- Electroencephalography/methods
- Humans
- Infant, Newborn
- Infant, Newborn, Diseases/diagnosis
- Infant, Newborn, Diseases/drug therapy
- Infant, Newborn, Diseases/etiology
- Infant, Newborn, Diseases/metabolism
- Infant, Newborn, Diseases/physiopathology
- Medication Therapy Management
- Video Recording/methods
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Loiacono G, Masci M, Zaccara G, Verrotti A. The treatment of neonatal seizures: focus on Levetiracetam. J Matern Fetal Neonatal Med 2014; 29:69-74. [DOI: 10.3109/14767058.2014.986651] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Wright C, Downing J, Mungall D, Khan O, Williams A, Fonkem E, Garrett D, Aceves J, Kirmani B. Clinical pharmacology and pharmacokinetics of levetiracetam. Front Neurol 2013; 4:192. [PMID: 24363651 PMCID: PMC3850169 DOI: 10.3389/fneur.2013.00192] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Accepted: 11/11/2013] [Indexed: 11/26/2022] Open
Abstract
Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam (IV LEV), a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available. Data have shown that it has a unique mechanism of action, linear pharmacokinetics and no known drug interactions with other anticonvulsants. In this paper, we will review the current literature about the pharmacology and pharmacokinetics of IV LEV and the safety profile of this new anticonvulsant in acute seizure management of both adults and children.
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Affiliation(s)
- Chanin Wright
- Division of Pharmacy, Department of Pediatrics, Scott & White Hospital and Texas A&M Health Science Center College of Medicine , Temple, TX , USA
| | - Jana Downing
- Division of Pharmacy, Department of Pediatrics, Scott & White Hospital and Texas A&M Health Science Center College of Medicine , Temple, TX , USA
| | - Diana Mungall
- Texas A&M Health Science Center College of Medicine , Temple, TX , USA
| | - Owais Khan
- Division of Neonatology, Department of Pediatrics, University of Chicago Medical Center , Chicago, IL , USA
| | - Amanda Williams
- Division of Pharmacy, Department of Pediatrics, Scott & White Hospital and Texas A&M Health Science Center College of Medicine , Temple, TX , USA
| | - Ekokobe Fonkem
- Department of Neurology, Scott & White Neuroscience Institute and Texas A&M Health Science Center College of Medicine , Temple, TX , USA
| | | | - Jose Aceves
- Division of Pediatric Neurology, Department of Pediatrics, Scott & White Hospital and Texas A&M Health Science Center College of Medicine , Temple, TX , USA
| | - Batool Kirmani
- Epilepsy Center, Department of Neurology, Scott & White Neuroscience Institute and Texas A&M Health Science Center College of Medicine , Temple, TX , USA
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