atypical presentation of neonatal seizures

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Correction - July 01, 1998

David Evans ,
Malcolm Levene
Division of Paediatrics and Child Health University of Leeds D Floor, Clarendon Wing General Infirmary Leeds Leeds LS2 9NS
Dr David Evans.Email: d.j.evans{at}leeds.ac.uk

https://doi.org/10.1136/fn.78.1.F70

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Neonatal seizures are common and may be the first manifestations of neurological dysfunction after a variety of insults. Neonatal seizures are clinically significant because very few are idiopathic. Further investigation leading to prompt diagnosis of the underlying condition is important because many of the aetiologies have specific treatments which, when used early, may improve the prognosis.

Neonatal seizures cause further neuronal compromise, but it is not clear whether this leads to further clinically significant neuronal injury in all, or even many seizures. Many of the clinical studies examining outcome associated with seizure activity have been confounded by the prognosis associated with the underlying aetiology. It is also unclear if adverse neurodevelopmental outcome, occurring as a consequence of seizures, can be prevented by current treatment. Many clinicians are therefore uncertain when to treat seizures and how to assess the adequacy of treatment. 1

The immature brain seems more prone to seizures; these are more common in the neonatal period than during any other time throughout life. This may reflect the earlier development of excitatory synapses, predominating over inhibitory influences at early stages of maturation. The incidence of clinical seizures in infants born at term is 0.7–2.7 per 1000 live births. 2-6 The incidence is higher in preterm infants, ranging from 57.5 to 132 per 1000 live births 3 7 (< 1500 g birthweight). The incidence of electrographic, clinically silent seizures is unknown. Continuous EEG monitoring of infants after one clinical seizure showed that 79% of subsequent EEG seizures were clinically silent. 8 Such phenomena seem to be more common in preterm infants. 6

Types of clinical seizure

A clinical seizure is a sudden, paroxysmal depolarisation of a group of neurones that results in a transient alteration in neurological state. This may involve abnormal motor, sensory, or autonomic activity, with or without a change in conscious …

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Guidelines & Reports
Archive of Draft Guideline Comments

Treatment of Seizures in the Neonate: Guidelines and Consensus-based Recommendations

The ILAE clinical practice guideline development group for neonatal seizures has developed guidelines and expert-based consensus recommendations for the treatment of neonatal seizures. These recommendations were informed by an extensive systematic review and, where no sufficient evidence was available, on expert-based consensus via Delphi. We are seeking your comments prior to submitting to a journal for peer review.

The systematic review identified 218 studies. The proposal includes guidelines and consensus-based recommendations on first and second line treatment, when to stop antiseizure medication, the impact of therapeutic hypothermia on seizure burden, and use of pyridoxine and pyridoxal 5´-phosphate. An example of a suggested treatment pathway including doses and adverse events based on current evidence and expert recommendations is given.

Draft : Treatment of Seizures in the Neonate: Guidelines and Consensus-based Recommendations – Special Report from the ILAE Task Force on Neonatal Seizures

Appendix A | Appendix B | Appendix C

Public comments are now closed and available for review below.

16 January 2023

Thank you very much for the work done, the evidence presented indicates that phenobarbital continues with the first option, leaving different options in the second line. What is not clear is whether using electroencephalographic monitoring when treating seizures what is referred to in some bibliography as seizure burden.

Rosa Y Alvarado M

13 January 2023

Thank you for compiling this important guidance. We would like to suggest some comments for your consideration.

There is no caveat included for the caution regarding the use phenytoin or carbamazepine as a second-line agent if a channelopathy is suspected (page 11) and further, for the incorporation of genetic testing in the treatment decision. While genetic variants in SCN1A and the associated Dravet Syndrome are unlikely to present in the neonatal period, we found that nearly 1% of the 800 neonates with seizures evaluated by a tested by a commercial genetic testing laboratory had a positive molecular diagnosis in SCN1A, for which the use of sodium-channel agents may not be appropriate (poster presented at the 2022 AES meeting by Grayson et al.)
For Ref 32: Painter et al 1997; Phenobarbital and Phenytoin met criteria for success in 13/30 (43%) and 13/29 (45%) as the initial agent, and when the other agent was added to the regimen for neonates whose seizures persistent, seizures were controlled with phenobarbital in 5/13 (39%) and phenytoin in 4/15 (27%) neonates.
For Ref 33: Sharpe et al 2020; Phenobarbital and Levetiracetam met criteria for success with dose escalation in 24/30 (80%) and 15/53 (28%) patients as the initial agent, and when the other agent was added to the regimen for neonates whose seizures persistent, seizures were controlled with phenobarbital in 20/37 (54%) and levetiracetam in 1/6 (17%) neonates, again with dose escalation in this second-line treated group.
Further, the information presented argues for phenobarbital to be considered in the list of second-line agents as well. Phenobarbital was the only ASM evaluated in the Delphi process that was not recommended by the experts as second-line treatment. Given that it is the choice of first line agent, we feel there should be a comment on why it wasn’t recommended, particularly as there may be patients started on a sodium channel agent (as recommended in the guidelines) and did not respond. These would be highly appropriate patients for phenobarbital use.
The recommendation (#3) to discharge babies whose seizures resolved off ASMs regardless of EEG and MRI findings is supported by the paper cited (ref 58). However, we think the response should be modulated somewhat, in that if seizures recur, obviously ASMs should be resumed. There is a chance that this recommendation could be taken too literally and could potentially obviate good clinical judgement.
Finally, the guidance states that the research priorities for the treatment of neonatal seizures includes dose finding, pharmacokinetic and safety studies in neonates, however, there are no recommendations regarding the preferred formulation of these ASMs. If an intravenous formulation is recommended, this should be specifically mentioned in addition to the acceptability of other routes of administration including intranasal and rectal use of ASMs.

Celene Grayson, PhD and Cynthia Harden, MD

11 January 2023

Dear ILAE Task Force:

Thank you for drafting this important document - these guidelines will be helpful to clinicians managing seizures in neonates. We would like to offer several points for your consideration.

The most recent search was done on 28 June 2020, and these guidelines are being drafted in 2023. We would suggest consideration of an updated search to ensure the most recent evidence is considered for these guidelines, and we have cited some of these publications. 1,2
The search strategy focusing on studies that include only electrographic seizures could potentially exclude studies that evaluated seizure response based on other important outcomes related to their safety. We understand this is important when evaluating the efficacy of seizure treatment on seizure burden and to avoid including seizure mimics. However, it excludes studies that provide insight into other relevant factors related to ASM treatment, such as adverse effects that may impact important outcomes such as mortality and neurodevelopment. Safety studies typically require large numbers of patients, and neonatal studies that only include patients with electrographic seizures are not sufficient powered to detect safety related issues. Phenobarbital and phenytoin have been shown to be neurotoxic in animal models. 3-5 Additionally, phenobarbital has been associated with decreased cognitive and motor scores in some studies of infants and young children. 6-8 As the ultimate goal of ASM treatment is not simply seizure cessation but long term outcome, a search strategy that excludes studies evaluating adverse effects ASM does not provide a complete picture of long-term outcome. We would suggest that future search strategies consider real-world evidence, where not all infants will undergo continuous EEG monitoring, into consideration of evidence. Access to continuous EEG monitoring that is interpreted by trained pediatric neurologists may be limited, even in high-resource settings. This is especially important if these guidelines are to be utilized in low and middle income countries.
The second-line treatment recommendations should consider risks such as mortality and neurodevelopmental outcome in recommendations between agents such as a phenytoin/fosphenytoin and levetiracetam. The current guideline draft states the level of evidence was very low for this recommendation and expert opinion was sought (with mixed results). As stated above, the authors’ search strategy limited to electrographic seizures excluded studies that could provide helpful information on adverse effects of ASMs. Adverse effects of phenytoin include arrhythmias, respiratory depression, and hypotension, which are serious and potentially lethal side-effects. 9 For example, a recent large US cohort study examined phenytoin compared to levetiracetam as second-line treatment following phenobarbital failure. 2 The comparative safety of these two medications in this study favors levetiracetam as second-line treatment.

Thank you for the opportunity to provide points for your consideration.

Dr. Elizabeth Sewell, Dr. Ravi Patel and Dr. Kaashif Ahmad

References :

Glass HC, Shellhaas RA. Safety of Early Discontinuation of Antiseizure Medication After Acute Symptomatic Neonatal Seizures-Reply. JAMA Neurol. 2022;79(1):91-92.
Sewell EK, Hamrick SEG, Patel RM, Bennett M, Tolia VN, Ahmad KA. Association between anti-seizure medication and outcomes in infants. J Perinatol. 2021.
Bittigau P, Sifringer M, Genz K, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci U S A. 2002;99(23):15089-15094.
Forcelli PA, Kim J, Kondratyev A, Gale K. Pattern of antiepileptic drug–induced cell death in limbic regions of the neonatal rat brain. Epilepsia. 2011;52(12):e207-e211.
Kaushal S, Tamer Z, Opoku F, Forcelli PA. Anticonvulsant drug–induced cell death in the developing white matter of the rodent brain. Epilepsia. 2016;57(5):727-734.
Maitre NL, Smolinsky C, Slaughter JC, Stark AR. Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures. Journal of Perinatology. 2013;33(11):841-846.
Farwell JR, Lee YJ, Hirtz DG, Sulzbacher SI, Ellenberg JH, Nelson KB. Phenobarbital for febrile seizures—effects on intelligence and on seizure recurrence. New England Journal of Medicine. 1990;322(6):364-369.
Sulzbacher S, Farwell JR, Temkin N, Lu AS, Hirtz DG. Late cognitive effects of early treatment with phenobarbital. Clinical pediatrics. 1999;38(7):387-394.
El-Dib M, Soul JS. The use of phenobarbital and other anti-seizure drugs in newborns. Semin Fetal Neonatal Med. 2017;22(5):321-327.

10 January 2023

Thanks to all for the wonderful work.

I think is accessible and affordable even in LMIC. Anyway only levet we’re preferred in cardiac condition so if there’s no levet in the case of seizure due to channel channelopathy what could be the anti seizure choice.

Dear ILAE Task force,

We congratulate for the efforts made in providing advances in neonatal seizures management; in particular, we appreciate with enthusiasm your efforts in underlining the importance of the EEG/aEEG as indispensable tools for seizure detection and believe that such inputs from the scientific community are needed to strengthen the possibility to have 24-7 skilled personnel available in all settings; furthermore, we believe it is fundamental, as you did, to underline the need to withdraw ASMs as soon as possible, ideally before discharge home (recommendation 3).

Unfortunately, we are concerned that more than one point needs to be further assessed.

With regard to recommendation 6, the authors state that a trial of pyridoxine should be provided as add-on to ASM in neonates with seizures unresponsive to second-line ASM without an identified etiology. Both our experience and various reports from the literature, though, support the possibility that patients with vitamin B6-dependent epilepsy might show an initial response to common ASMs to, later, relapse with status epilepticus. 1,2 We believe updated guidelines should look deeper into this matter and suggest considering a trial of pyridoxine in all patients with seizures of unknown etiology as first-line treatment, even before ASMs’ administration, especially in neonates presenting with clinical features or EEG characteristics suggestive of vitamin B6- dependent epilepsy.

Furthermore, the authors’ enthusiasm in providing 'high' consensus-based evidence that Phenobarbital should always be administered as first-line ASM seems a bit incautious (recommendation 1). Historically, Phenobarbital has been largely used and this unavoidably justifies the high amount of literature available on its efficacy rates and side-effects. On the other hand, though, the scientific community has pronounced for decades on Phenobarbital’s long-term detrimental side effects on neurodevelopment. We believe the fact that to date there’s no 'universally' more effective alternative does not justify Phenobarbital’s administration in all patients, as suggested in your paper, even in those with low seizure burden, electrical only seizures or short, self-limiting seizures. It would probably be more prudent to at least address this issue in the paper and to underline the need to consider Phenobarbital’s side effects and inform parents when the decision to prescribe it is made. Furthermore, in your paper Phenobarbital is suggested as first choice in all cases but its’ overall efficacy remains quite unsatisfactory; this, unavoidably raises doubts and questions in readers. What the scientific community and clinicians worldwide expect is not anymore the 'holy grail' of neonatal seizures treatment, a medication that works for all patients, regardless of the underlying etiology and seizures features but the possibility to point towards a targeted, precision medicine; in 2021 our group published a systematic review on ASMs’ efficacy in treating neonatal seizures from different etiologies and found, among 66 included studies, that the same ASM provided different efficacy rates in different population of newborns, that were grouped altogether not by the ASM used, as in your paper, but by the underlying etiology. 3 In particular, some data pointed towards an overall satisfactory efficacy of Lidocaine for stroke, SCB for genetic channelopathies – as you well underlined – Lev for HIE and found that Lev was safe both in term and preterm newborns and in terms of both short- and long-term outcomes, not only in patients with cardiac comorbidities as you underlined based mainly on expert opinions. Indeed, the small number of patients enrolled and the not-so rigid methodology of most studies included both in our and in your work probably does not allow to replace current protocols but we feel the need for updated guidelines, such as yours, to support the efforts made by clinicians worldwide to point towards a precision therapy and feel concerned that the paper you provided does not completely follow the trend that clinical practice has conquered in the last years and risks perpetuating management strategies that have been shown to be unsatisfactory and in some cases even harmful.

Raffaele Falsaperla & Bruna Scalia

Kluger G, Blank R, Paul K, Paschke E, Jansen E, Jakobs C, Wörle H, Plecko B. Pyridoxine-dependent epilepsy: normal outcome in a patient with late diagnosis after prolonged status epilepticus causing cortical blindness. Neuropediatrics. 2008 Oct;39(5):276-9. doi: 10.1055/s-0029-1202833. Epub 2009 Mar 17. PMID: 19294602.
Lin J, Lin K, Masruha MR, Vilanova LC. Pyridoxine-dependent epilepsy initially responsive to phenobarbital. Arq Neuropsiquiatr. 2007 Dec;65(4A):1026-9. doi: 10.1590/s0004-282x2007000600023. PMID: 18094870.
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 Apr 7;47(1):85. doi: 10.1186/s13052-021-01027-2. PMID: 33827647; PMCID: PMC8028713.

4 January 2023

The authors are to be congratulated for going forward on the path of preventing overtreatment by advocating discontinuation of antiseizure medication (ASM) before discharge home in infants who showed cessation of acute symptomatic seizures ( recommendation 3 ). However, their enthusiasm for phenobarbital as a first-line ASM ( recommendation 1 ) and treatment of all neonatal seizures including electrographic-only seizures ( recommendation 5 ) cause concern.

Phenobarbital has been shown to display considerable neurotoxicity in numerous animal models both in rodents and in monkeys. In newborn mice, a dosage of phenobarbital that reduces seizure burden in hypoxia-induced seizures (25 mg/kg) lacks any positive effect on histopathological injury, behavioral abnormality, or impaired memory function. 1 In neonatal rats with status epilepticus, phenobarbital and midazolam even worsen neuronal injury. 2 In neonatal rhesus monkeys, extensive degeneration of neurons and oligodendrocytes has been observed in various brain regions following the administration of phenobarbital and midazolam 3 that is not ameliorated by hypothermia. 4 A retrospective study of 280 human infants who were given ASM for neonatal seizures, a cumulative exposure of 100 mg phenobarbital/kg was associated with 8-9 points decrease of the Bayley Scales of Infant Development scores at 2 years of age, while the probability of cerebral palsy increased more than 2-fold. 5 Furthermore, low-dose phenobarbital (5 mg/kg/d) given prophylactically to infants and young children was associated with a decline of the intelligence quotient by 5-8 points in a large placebo-controlled randomized controlled trial. 6 Thus, phenobarbital may be the most efficacious ASM but its administration exerts considerable damage to the developing brain. Possibly, this is the price to pay for infants with heavy seizure burden, but for infants with short, self-limiting seizures, the remedy may be more dangerous than the disease.

Seizures by themselves have not been found to be linked to impaired neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy. 7,8 As overall seizure burden is a marker of the extent of brain damage, the association between high seizure burden and neurodevelopmental impairment is trivial. Prolonged seizures appear to herald rather than cause poor outcome, at least in the setting of hypoxic-ischemic encephalopathy. Data from two prospective randomized controlled trials involving 33 infants 9 and 172 infants, 10 respectively, failed to suggest that treatment of subclinical seizures improves outcome in newborns with acute symptomatic seizures, contravening recommendation 5. Efforts aimed at stopping all seizures as rapidly and effectively as possible may do more harm than good.

Christoph Bührer

Quinlan SMM, Rodriguez-Alvarez N, Molloy EJ, Madden SF, Boylan GB, Henshall DC, Jimenez-Mateos EM. Complex spectrum of phenobarbital effects in a mouse model of neonatal hypoxia-induced seizures. Sci Rep 2018;8(1):9986. doi: 10.1038/s415980‑18‑28044-2.
Torolira D, Suchomelova L, Wasterlain CG, Niquet J. Phenobarbital and midazolam increase neonatal seizure-associated neuronal injury. Ann Neurol 2017;82(1):115-120. doi: 10.1002/ana.24967.
Noguchi KK, Fuhler NA, Wang SH, Capuano S 3rd, Brunner KR, Larson S, Crosno K, Simmons HA, Mejia AF, Martin LD, Dissen GA, Brambrink A, Ikonomidou C. Brain pathology caused in the neonatal macaque by short and prolonged exposures to anticonvulsant drugs. Neurobiol Dis 2021;149:105245. doi:10.1016/j.nbd.2020.105245.
Ikonomidou C, Wang SH, Fuhler NA, Larson S, Capuano S 3rd, Brunner KR, Crosno K, Simmons HA, Mejia AF, Noguchi KK. Mild hypothermia fails to protect infant macaques from brain injury caused by prolonged exposure to antiseizure drugs. Neurobiol Dis 2022;171:105814. doi: 10.1016/j.nbd.2022.105814.
Maitre NL, Smolinsky C, Slaughter JC, Stark AR. Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures. J Perinatol 2013;33(11):841-6. doi: 10.1038/jp.2013.116.
Farwell JR, Lee YJ, Hirtz DG, Sulzbacher SI, Ellenberg JH, Nelson KB. Phenobarbital for febrile seizures--effects on intelligence and on seizure recurrence. N Engl J Med 1990;322(6):364‑9. doi: 10.1056/NEJM199002083220604.
Kharoshankaya L, Stevenson NJ, Livingstone V, Murray DM, Murphy BP, Ahearne CE, Boylan GB. Seizure burden and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy. Dev Med Child Neurol 2016;58(12):1242‑1248. doi: 10.1111/dmcn.13215.
Basti C, Maranella E, Cimini N, Catalucci A, Ciccarelli S, Del Torto M, Di Luca L, Di Natale C, Mareri A, Nardi V, Pannone V, Di Fabio S. Seizure burden and neurodevelopmental outcome in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia: A single center observational study. Seizure 2020;83:154-159. doi: 10.1016/j.seizure.2020.10.021.
van Rooij LG, Toet MC, van Huffelen AC, Groenendaal F, Laan W, Zecic A, de Haan T, van Straaten IL, Vrancken S, van Wezel G, van der Sluijs J, Ter Horst H, Gavilanes D, Laroche S, Naulaers G, de Vries LS. Effect of treatment of subclinical neonatal seizures detected with aEEG: randomized, controlled trial. Pediatrics 2010;125(2):e358-66. doi: 10.1542/peds.2009-0136.
Hunt RW, Liley HG, Wagh D, Schembri R, Lee KJ, Shearman AD, Francis-Pester S, de Waal K, Cheong JYL, Olischar M, Badawi N, Wong FY, Osborn DA, Rajadurai VS, Dargaville PA, Headley B, Wright I, Colditz PB; Newborn Electrographic Seizure Trial Investigators. Effect of treatment of clinical seizures vs electrographic seizures in full-term and near-term neonates: a randomized clinical trial. JAMA Netw Open 2021;4(12):e2139604. doi: 10.1001/jamanetworkopen.2021.39604.

25 December 2022

Nice work from the ILAE task Force.

Dr Sameer Zuberi visited Aga Khan University Hospital a month ago. Since then, we have started collecting data regarding recurrence of seizures in HIE noenatal age groups.

Although the majority of RCTs mentioned in this report are based on clinical seizures, electroclinical and specifically electrographic seizures are still topics of concern in a major part of world.

I question that in developing countries the majority of HIE neonates are Grade III, and suddenly withdrawing ASMs may result in recurrence.

Data from developing countries are still lacking. Early discontinuation of ASMs should be individualized in certain conditions.

Dr. Farhan Ali

20 December 2022

Thank you for this excellent work.

Dear Madam or Sir,

The draft mentions sodium channel blockers as a treatment options, but lists only phenytoin and carbamazepine as possible choices. Are there any reasons not to mention oxcarbazepine (which is, at least in Germany, nowadays much more widely used than carbamazepine) and lacosamide?

Sincerely yours,

Moritz Tacke

This is a valuable effort. The sentence on page 10 of the introduction [Electroencephalography (EEG or aEEG) is required for seizure diagnosis since most seizures in neonates have no clinical manifestations (electrographic-only)...] is very important.

EEG is not yet provided in many NICUs at point of diagnosis. I suggest more emphasis on need for EEG for certain diagnosis and to determine AED treatment duration in neonatal seizures.

David Rowitch

19 December 2022

I have great worries about consensus based guidelines as they risk perpetuating treatments or management protocols that may ultimately be shown to be harmful or ineffective. A non-evidenced based guideline risks imposing a harmful or dangerous treatment on ALL infants; this was the case for example with routine use of 100% oxygen for newborn resuscitation, a practice that was enshrined in consensus/expert opinion based guidelines which harmed countless babies. However, I recognise that all too often, evidence to support clinical practice is insufficient and also that consistency of practice within a centre has some benefits. Therefore when evidence is insufficient for an evidence-based guideline I strongly recommend that the authors include the following statements in their document: 1) the treatment uncertainties should be explained to parents; 2) it should be made explicit to neonatal centres that the existence of a guideline does not mean they cannot take part in a randomised controlled trial to address the treatment uncertainty; 3) all neonatal centres should be strongly advised to join high quality randomised studies to resolve such uncertainties; and 4) it should be explained to parents that in the face of uncertainty, randomisation is the most fair and ethical approach as it is the only way to provide every baby with an equal chance of receiving the (unknown) best treatment.

I appreciate the great effort from the authors to provide us with this recommendations. I would like to ask, if it is possible to address the following concerns:

Treatment as a rescue-option in newborns with CNS insult and seizure-like activity that are being transported or waiting for transport to a specialized NICU center (an agent that will not interfere with the exam/EEG or with a short half-life).
In acute metabolic disturbances and seizures (glycemia or electrolytes) ASM should be started while the metabolic issue is being corrected?
Lidocaine should not be used if phenytoin was previously used.
Treatment options/recommendations in refractory-seizures or neonatal status epilepticus after using 1st and 2nd line agents.

Oscar DeLaGarza

17 December 2022

Thank you. The methodology and scope for the recommendations is excellent.

I find some of the recommendations confusing, and I think need to be clearer particularly if aimed at non-neurology neonatal professionals in an acute/emergency setting.

Recommendation 1 implies all should have phenobarbital, but then outlines an exception. This is confusing.

Where citing sodium channel ASMs in a recommendation would be good to always list the examples as many will not think of ASMs in this way. In fact I would simply list the suitable drugs to consider rather than refer to them by this category.

For the first line ASM it implies solely family history of channelopathy is factor, whereas for second line, solely electro-clinical features of channelopathy in index case are important. Is this the intention?

I would like to be guided within the guidance as to the definition of channelopathy and what should make me consider a channelopathy in practice, given is a key determinant of different ASMs. Many will not be familiar with this channelopathy term.

The flow diagram arrows are confusing and is hard to follow the logic. The vertical arrows imply next step or decision. The horizontal arrows imply caveats rather than a next step. I think a decision tree approach might make this much clearer so that you can follow through ASM choices based on presence or absence of the key caveats.

Colin Dunkley

15 December 2022

Dear ILAE Task Force,

I have gone through the consensus based recommendations for treatment of seizures in the neonates. Phenobarbitone is known to have negative neurodevelopmental effect especially on the developing brain, recommending it as first line treatment for seizure control needs further clarification in terms of duration and dosage and what should be our end point, clinical seizure control or electrographic improvement. Also stopping anti-seizure medications before discharge irrespective of neurological and electrographic changes needs further research and recommendations. The role neuroimaging can play an important role. The loading and maintenance dosage of levetiracetam also needs clarification.

Dr Rahul Sinha Pediatric Neurologist Command Hospital Chandimandir Panchkula Haryana India

The manuscript looks excellent and the recommendations are reasonable.

Dr Shripada Rao

13 December 2022

Role of EEG and aEEG especially in LMIC settings for management of Neonatal seizures should be clarified.

Rohit Anand

Indication for midazolam infusion, dose and escalation and tapering protocol.

Mayank Priyadarshi

Refractory seizures can be the first choice of treatment with oxcarbamazepine in channelopathy.

Rafid Abdulkadhim Atshan Alneghimsh

I am concerned that the first recommendation - that in neonates with seizures requiring antiseizure medication (ASM), phenobarbital should be the first-line ASM, does not highlight the fact that this is based only on data regarding seizure cessation efficacy, and we do not know if it will ultimately improve neurodevelopmental outcome- the ultimate endpoint we care about.

Although phenobarbital has proven highly effective at achieving seizure cessation, its net effect on neurodevelopment could still be negative, due to its neurotoxic effects.

Rat and primate neonatal studies have shown markedly accelerated neuronal apoptosis following a single standard dose of phenobarbital, (and most other antiseizure medications, phenytoin, midazolam, valproate). Other adverse effects caused by phenobarbital in the animal model include interference with cell proliferation and migration, axonal arborization, synaptogenesis and synaptic plasticity. 1-6

Fetal exposure has been shown to reduce cognitive outcomes in 2 case control studies. The magnitude of the effect was about 0.5 standard deviations. 7

Young children randomized to PHB for febrile seizure had persistently lower IQ test results after medications tapered. 8-11

This month at Neonatal Hot Topics conference, 7 December 2022, Washington DC Professor Rod Hunt, presented additional, yet unpublished, data from his recent study on the impact of aEEG monitoring on neurodevelopmental outcome. 12 This showed a dose dependent adverse impact of phenobarbital on IQ, a 3pt IQ drop for every 10 mg/kg phenobarbital received. On average in his cohort, neonates received 38 mg/kg of PHB. This association held after correction for the underlying severity of injury and for seizure burden.

Additionally, the recommendation does not not define when seizures require antiseizure medication.

A summary of the evidence that seizures are harmful per se and the remaining gaps in that evidence should be included in this guideline.

It should be highlighted that our evidence that seizures are harmful is most convincing for prolonged seizures in both animal and human studies. 13-16 In patients with low seizure burden, neurodevelopmental outcome is frequently normal. Boylan et al 17 demonstrate that a cut off maximal seizure burden of 13 minutes/ hour or total seizure burden of 40 minutes separate patients with abnormal outcomes from those with normal outcomes. In NEOLEV2 more than half the cohort had seizure burdens less than this.

It remains unclear in patients with low seizure burden, whether the risk of neurologic injury from the seizures is greater than the risks of neurotoxic injury from phenobarbital.

Unedited, the draft recommendation will lead to widespread increased use of phenobarbital for all neonatal seizures, potentially doing more harm than good.

Yours sincerely,

Dr Cynthia Sharpe NEOLEV2 Investigator

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Forcelli PA, Kim J, Kondratyev A, Gale K. Pattern of antiepileptic drug-induced cell death in limbic regions of the neonatal rat brain. Epilepsia. 2011;52(12):e207-11.
Forcelli PA, Janssen MJ, Vicini S, Gale K. Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development. Ann Neurol. 2012;72(3):363-72.
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Reinisch JM, Sanders SA, Mortensen EL, Rubin DB. In utero exposure to phenobarbital and intelligence deficits in adult men. JAMA. 1995;274(19):1518-25.
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Sulzbacher S, Farwell JR, Temkin N, Lu AS, Hirtz DG. Late cognitive effects of early treatment with phenobarbital. Clin Pediatr (Phila). 1999;38(7):387-94.
Calandre EP, Dominguez-Granados R, Gomez-Rubio M, Molina-Font JA. Cognitive effects of long-term treatment with phenobarbital and valproic acid in school children. Acta Neurol Scand. 1990;81(6):504-6.
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Thank you for the interesting study and is very needed in practice.

My comments:

Page 10 needs to be clarified: 'Only one study with phenobarbital and levetiracetam used standardized adverse events tables and reported that there was a trend towards hypotension being more common with phenobarbital (n=17%) compared to levetiracetam (n=5%)'.
Why is the Neonatal hypoglycemia not mentioned or included in the draft discussion?

Murad Al-Nusaif

12 December 2022

Clear guidelines need for the management of convulsive non convulsive status epileptics in neonates. Use of anesthetic agents, intranasal and rectal use of ASM can be mentioned.

Prof.Dr. M.A.Aleem

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Neonatal seizures associated with a severe neonatal myoclonus like dyskinesia due to a familial KCNQ2 gene mutation

Affiliation.

1 Pediatric Neurology Unit, Wolfson Medical Center, Holon, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
PMID: 22169383
DOI: 10.1016/j.ejpn.2011.11.004

Mutations in the potassium channel gene KCNQ2, usually cause benign familial neonatal epilepsy. This is an autosomal dominant disorder characterized by clusters of seizures occurring in the first days of life. Most patients have normal psychomotor development and spontaneous remission of seizures by 12 months of age. Since Rett and Teubel reported the first family in 1964 and the identification of KCNQ2 gene mutations in this family by Zimprich et al. in 2006, phenotypic variability has been recognized including: later onset of seizures, myokymia in isolation or accompanied by seizures, neurological deficit and mental retardation. We report a mother and son with an atypical presentation of familial neonatal epilepsy. The mother has persistent epilepsy and subnormal intelligence. The son developed a severe dyskinesia clinically compatible with multifocal myoclonus in the neonatal period that only responded to carbamazepine. He also has ataxia and delayed psychomotor development. EMG revealed a spontaneous occurrence of repetitive normal motor potentials in different muscle groups. Genetic analysis identified a heterozygous missense mutation in KCNQ2 in the child and his mother.

Conclusion: KCNQ2 mutations can present with a neonatal onset multifocal myoclonus-like dyskinesia.

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Cocaine- and levamisole-induced vasculitis: defining the spectrum of autoimmune manifestations.

1. Introduction

1.1. cocaine, 1.2. levamisole, 2. pathogenesis of cocaine- and levamisole-related disorders, 2.1. direct nasal trauma and vascular ischemia, 2.2. immune-system dysregulation via neutrophils and nets, 2.3. production of autoantibodies, 3. clinical presentation of levamisole- and cocaine-induced disorders, 3.1. cocaine-induced midline destructive lesion (cimdl), 3.1.1. clinical features, 3.1.2. histopathology, 3.1.3. laboratory findings, 3.1.4. imaging, 3.2. cocaine-induced vasculitis (civ), 3.2.1. clinical features, 3.2.2. histopathology, 3.2.3. laboratory findings, 3.3. levamisole-adulterated cocaine (lac) vasculopathy/vasculitis, 3.3.1. clinical features, 3.3.2. histopathology, 3.3.3. laboratory findings, 4. differential diagnosis, 5. treatment, 6. conclusions, author contributions, institutional review board statement, data availability statement, conflicts of interest.

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Click here to enlarge figure

Classification Grade	Localization	Patients in the Nitro et al. [ ] Systematic Review
1 (middle)	Nasal septum	126 (99.2%)
2 A (inferior third of the sinonasal complex)	Grade 1 + inferolateral district (inferior turbinate and Maxillary-sinus medial wall, nasolacrimal duct)	75 (59%)
2 B (inferior third of the sinonasal complex)	Grade 1 + palate (nasal floor)	38 (29.9%)
3 (middle third of the sinonasal complex)	Grade 2 + ethmoid bone, middle turbinate and superior turbinate	29 (22.8%)
4 (neurocranial structures)	Grade 3 + neurocranium (lamina papyracea, orbit base or skull base)	10 (7.9%)

CIMDLs	LAC Vasculopathy/Vasculitis	CIV
ENT (midline structures)	Local (cutaneous) and systemic	Multi-organ and systemic
Diffuse necrotizing ulcerative lesions, nasal crusting, nasal-septum perforation, palatal perforation, nasal deformity	Retiform purpura, constitutional symptoms, midline destructive lesions, glomerulonephritis, pulmonary involvement, leukoencephalopathy, arthritis	Skin rashes, joint involvement, pauci-immune crescentic glomerulonephritis, alveolar hemorrhage
Perinuclear or cytoplasmatic	Atypical perinuclear	Perinuclear
Anti-HNE, PR3-ANCA, ANCA negative	MPO-ANCA, PR3-ANCA, anti-HNE	PR3-ANCA, MPO-ANCA, ANCA negative
HNE and PR3	c-ANCA and p-ANCA	PR3 and p-ANCA
-	APL, low complement levels, ANAs, anti-dsDNA, anti-C1q, cryoglobulin	-
Rarely	Common	Common
None	Common (leukopenia, neutropenia, agranulocytosis, hemolytic anemia, thrombocytopenia)	-
Not specific except for cell apoptosis and extensive necrosis	Thrombotic vasculopathy, leukocytoclastic vasculitis	Leukocytoclastic vasculitis, commonly pauci-immune necrotizing glomerulonephritis
Cessation of cocaine abuse	Cessation of cocaine abuse	Cessation of cocaine abuse
Rarely required, only in case of systemic inflammation	Required in case of severe systemic inflammation or life-threatening symptoms	Controversial
Conservative local treatment, prosthetic and reconstructive surgery	Supportive local therapy and plastic surgery	-

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Share and Cite

Iorio, L.; Davanzo, F.; Cazzador, D.; Codirenzi, M.; Fiorin, E.; Zanatta, E.; Nicolai, P.; Doria, A.; Padoan, R. Cocaine- and Levamisole-Induced Vasculitis: Defining the Spectrum of Autoimmune Manifestations. J. Clin. Med. 2024 , 13 , 5116. https://doi.org/10.3390/jcm13175116

Iorio L, Davanzo F, Cazzador D, Codirenzi M, Fiorin E, Zanatta E, Nicolai P, Doria A, Padoan R. Cocaine- and Levamisole-Induced Vasculitis: Defining the Spectrum of Autoimmune Manifestations. Journal of Clinical Medicine . 2024; 13(17):5116. https://doi.org/10.3390/jcm13175116

Iorio, Luca, Federica Davanzo, Diego Cazzador, Marta Codirenzi, Eleonora Fiorin, Elisabetta Zanatta, Piero Nicolai, Andrea Doria, and Roberto Padoan. 2024. "Cocaine- and Levamisole-Induced Vasculitis: Defining the Spectrum of Autoimmune Manifestations" Journal of Clinical Medicine 13, no. 17: 5116. https://doi.org/10.3390/jcm13175116

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v.7(3); 2017 Jul

Term Neonate with Atypical Hypoxic-Ischemic Encephalopathy Presentation: A Case Report

Nick townley.

1 Division of Neonatology, Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri

Emily McNellis

Venkatesh sampath.

We describe a case of atypical hypoxic-ischemic encephalopathy (HIE) in a neonate following a normal pregnancy and delivery who was found to have an umbilical vein thrombosis. The infant arrived to our center with continuous bicycling movement of her lower extremities. She had a continuous electroencephalogram that showed burst suppression and magnetic resonance imaging of the brain showed diffusely abnormal cerebral cortical/subcortical diffusion restriction which may be secondary hypoxic-ischemic injury. Interestingly, a pathology report noted a focal umbilical vein thrombosis appearing to have compressed an umbilical artery with associated arterial dissection and hematoma. Our case illustrates how umbilical venous or arterial thrombosis may be associated with HIE and refractory seizures.

Hypoxic-ischemic encephalopathy (HIE) occurs in 2.5 per 1,000 term births making it a common admission diagnosis in tertiary neonatal intensive care units (NICUs). 1 Neonates with HIE can have a history of birth trauma, birth difficulty, or depression after delivery but not in all cases. 2 We describe a case of atypical HIE in a neonate following a reportedly normal pregnancy and delivery who was subsequently found to have an umbilical vein thrombosis.

Case Presentation

A female infant was born by spontaneous vaginal delivery at 41 weeks of gestation to a 25-year-old gravida 2, para 2 mother. The mother was obese but otherwise healthy, had received routine prenatal care, and had no history of previous miscarriages. Her first pregnancy was unremarkable and the family had a healthy 3-year-old child. Delivery history was significant for premature rupture of membranes for 22 hours. There were no concerns on prenatal ultrasounds nor evidence of fetal instability during the delivery process. There was no family history of thrombosis or clotting disorders. The infant's birth weight was 3.4 kg, head circumference 34.5 cm, and length 49.5 cm, all appropriate for gestational age. A nuchal cord was wrapped two times, that was easily reduced, and the mother had a temperature of 39.2°C at delivery. Apgar scores were 2 at 1 minute, 6 at 10 minutes, and 8 at 10 minutes of life. Poor scores were due to inadequate respiratory effort, and the infant was tracheally intubated in the delivery room. The infant's heart rate did not drop below 60 and was above 100 with positive pressure ventilation. Cord gases were unremarkable (arterial pH 7.24/base excess [BE] −6 and venous pH 7.32/BE −8) and the initial arterial blood gas after intubation was 7.24/18/104/−16 showing partially compensated metabolic acidosis.

The infant was on low conventional ventilation settings and was extubated after being moved to the NICU. Chest film was unremarkable. Hemodynamically, the infant was stable for the first 8 hours of life. After 8 hours of life, her family and clinicians were concerned about posturing movement, apnea, and desaturations. The infant was transferred to a regional referral NICU after being given a loading dose of phenobarbital. The physical exam after arriving to the referral center was notable for increased upper extremity tone, static extension of both upper extremities, and a continuous bicycling movement of her lower extremities. The exam at 10 hours of life was consistent with encephalopathy and status epilepticus. She was intubated to support her airway and an umbilical venous line was placed.

Clinical and amplitude-integrated electroencephalogram (aEEG) monitored seizures were refractory and required escalation of seizure medication until a midazolam-induced coma was initiated and seizures resolved. She remained on low ventilator settings. She was monitored by continuous EEG that showed burst suppression ( Fig. 1 ). Magnetic resonance imaging (MRI) of the brain at 22 hours of life showed diffusely abnormal cerebral cortical/subcortical diffusion restriction which may be secondary hypoxic-ischemic injury ( Fig. 2 ). As this infant did not appear symptomatic until 8 hours of life, and admission to the tertiary center did not occur until 10 hours of life, therapeutic cooling was not pursued.

An external file that holds a picture, illustration, etc.
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Electroencephalogram with burst suppression.

An external file that holds a picture, illustration, etc.
Object name is 10-1055-s-0037-1605372-i160079-2.jpg

Magnetic resonance imaging of the brain showing diffusely abnormal restricted diffusion throughout the cerebral cortex involving the bilateral frontal, bilateral parietal, left greater than right occipital, and temporal regions, predominantly in the cortex and subcortical white matter. The edema in this image shows the event was a global insult.

Infectious diseases or inborn errors of metabolism, while rare, can present as an atypical case of HIE. In this case, cerebral spinal fluid evaluation revealed unremarkable neurotransmitter, amino acid and cell count profiles, negative herpes simplex virus types 1 and 2, and bacterial and common viral cultures. Urine analysis was negative for organic acids and ketones, and serum revealed normal levels for ammonia, acylcarnitine, pyruvate, sulfocysteine, and amino acids profile. On day 7 of life, a pathology report noted a focal umbilical vein thrombosis appearing to have compressed an umbilical artery with associated arterial dissection and hematoma. Normal cord length, without other cord or placental anomalies was noted and development of the event was suggested to have been sudden per pathologist. Given the atypical presentation of HIE, this suggested the etiology of the patient's presentation. After a 2-day midazolam wean, the infant was discharged to home hospice on day 9 of life continuing maintenance phenobarbital. Her mother was to undergo a screening evaluation for a possible inherited thrombophilia disorder.

HIE can be traceable to an antenatal or perinatal event such as abruption or cephalopelvic disproportion. 2 Atypical presentations have been associated with inborn errors of metabolism (urea cycle disorders, organic and amino acid disorders, glutaric aciduria) or meningitis. All were screened for and ruled out in our patient. Umbilical cord thrombosis has been reported and is correlated with additional umbilical cord abnormalities. 3 4 Its incidence is estimated to occur in 1 of 1,300 deliveries, 5 and there are a few reports on cord vessel dissection and thrombosis resulting in HIE, 6 7 stillbirth, or complicated NICU course. 8 The case presented broadens the potential etiologies of HIE and underscores the importance of pathological evaluation of the placenta and umbilical cord in these cases.

Reported risk factors for thrombosis in the fetus or products of conception include maternal diabetes, 3 nuchal cord, 4 6 and maternal obesity with the latter two risk factors present in our patient. The initial thrombotic event may then have been associated with vascular congestion, hypovolemia, hypoxia, and anemia, thus leading to neurological injury that later presented with seizures. In one animal study, intermittent partial cord occlusions in fetal lambs led to death in one-third of the subjects and high rates of status epilepticus and EEG suppression in the survivors, similar to our case. 9

The patient's perinatal history, Apgar scores, initial blood gas, and reassuring cord gases did not guarantee an acute perinatal event making clinical association necessary in determining the cause of intrapartum hypoxia. As the timing of the neurological injury could not be elucidated by MRI, the initial injury may have been remote allowing some recovery prior to delivery or immediately preceding delivery, not allowing acidosis to develop. The normal cord gases could suggest such recovery via recanalization and re-establishment of sufficient perfusion.

HIE is a common presentation to referral NICUs that can be linked to a history of a traumatic event at birth and less commonly with metabolic or infectious causes. Our case is unique because the presentation of HIE and refractory seizures is associated with umbilical venous thrombosis. This presentation is atypical for HIE but important for clinicians to consider during a neurological insult work-up. This case highlights that while history and work-up are important, pathological evaluation for placental and umbilical cord abnormalities may be just as vital in the search of an etiology for atypical presentations of HIE, thus broadening the differential in a common NICU diagnosis.

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EPIDEMIOLOGY. Seizures occur more often in the neonatal period than at any other time of life; during this period, they most often occur within the first week of life [ 1,2 ]. Reported incidence ranges from 1.5 to 5.5 per 1000 in newborns [ 2-4] and may be even higher in premature infants [ 5,6 ]. Seizure incidence varies with some specific ...
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Neonatal seizures are a commonly encountered neurologic condition in neonates.[1][2][3] They are defined as sudden, paroxysmal, abnormal alterations of electrographic activity from birth to the end of the neonatal period.[3] During this period, the neonatal brain is developmentally immature.[4][5] Thus, neonatal seizures have unique pathophysiology and electrographic findings resulting in ...
Seizures in the neonate: A review of etiologies and outcomes
Seizures are the most frequent neurological sign observed in the neonatal intensive care unit and occur in their majority in close temporal relation to an acute brain injury or systemic insult, with or without identifiable structural abnormalities [1]. These events are defined as acute symptomatic or provoked seizures. Although these two terms are often used interchangeably, acute symptomatic ...
Neonatal seizures: diagnostic updates based on new definition and
Introduction. Neonates are most susceptible to seizure development due to their brain immaturity and high risk of injury [1,2].Neonatal seizures, a most common neurological condition, are associated with high mortality rates of up to 20% [1,2].Neonatal seizures can lead to long-term outcomes such as epilepsy, cerebral palsy, developmental disabilities, and psychomotor impairments depending on ...
Current Overview of Neonatal Convulsions
According to clinical findings, 4 types of seizures may be observed in the neonatal period: subtle, clonic, tonic, and myoclonic seizures. Subtle (unspecified) seizure is the most common type of convulsion. It includes movements such as a tremor in the eyelids; a fixed gaze in the eyes or horizontal deviation; smacking, chewing, or other oral ...
Neonatal Seizures
Neonatal Seizures. Pediatr Rev (2024) 45 (7): 381-393. Neonatal seizures are difficult to recognize clinically and require electroencephalographic monitoring for accurate diagnosis; 60% to 80% of confirmed electrographic seizures in neonates are subclinical, with no outwardly visible signs detectable by bedside caregivers.
Neonatal Seizures
DOI: 10.1056/NEJMra2300188. VOL. 388 NO. 18. Neonatal seizures are defined as seizures occurring within 4 weeks after birth in full-term infants or within 44 weeks of postmenstrual age in preterm ...
PDF Neonatal seizures: diagnostic updates based on new definition and
388 Kim EH, et al. Diagnosis of neonatal seizures by new definition and classification www.e-cep.org immature they are, the shorter the seizures and the higher the proportion of subclinical or electrographiconly seizures. Thus, EEG is essential for diagnosis. 10,15,24) Etiologies Many etiologies can cause neonatal seizures, although only a
Neonatal seizures
A seizure is caused by sudden, abnormal and excessive electrical activity in the brain. By definition, neonatal seizures occur during the neonatal, or newborn, period. For a full-term infant, this is the first 28 days after their birth. Most of these seizures occur within the first week of a baby's life. Premature or low birth weight babies are ...
Neonatal Seizures N
Neonatal. seizures are defined as seizures occurring within. 4 weeks after birth in full-term infants or within 44 weeks of postmen-strual age in preterm infants. The estimated incidence of these ...
Neonatal seizures
Neonatal seizures are common and may be the first manifestations of neurological dysfunction after a variety of insults. Neonatal seizures are clinically significant because very few are idiopathic. Further investigation leading to prompt diagnosis of the underlying condition is important because many of the aetiologies have specific treatments which, when used early, may improve the prognosis ...
Seizures in the neonate: A review of etiologies and outcomes
Neonatal seizures are a frequent clinical manifestation in the neonatal period and they can present within the framework of four clinical scenarios, each with a distinct post-neonatal evolution (Fig. 1).In scenarios A, C, and D, neonatal seizures correspond to acute symptomatic seizures that may be self-limiting (A), initially stop but eventually evolve after a latent period in post-neonatal ...
Clinical manifestations of neonatal seizures
Abstract. Neonatal seizures present a unique diagnostic challenge with clinical manifestations often subtle or absent to the bedside observer. Seizures can be overdiagnosed in newborns with unusual paroxysmal movements and underdiagnosed in newborns without clinical signs of seizures. Electroclinical "uncoupling" also adds to the diagnostic ...
Treatment of Seizures in the Neonate: Guidelines and Consensus-based
4 January 2023. The authors are to be congratulated for going forward on the path of preventing overtreatment by advocating discontinuation of antiseizure medication (ASM) before discharge home in infants who showed cessation of acute symptomatic seizures (recommendation 3).However, their enthusiasm for phenobarbital as a first-line ASM (recommendation 1) and treatment of all neonatal seizures ...
Guidelines on Neonatal Seizures
The designations employed and the presentation of the material in this publication do not imply the ... Neonatal seizures, one of the most frequent neurological events in newborn infants, reflect a variety of pre-, peri- or postnatal disorders of the central nervous system (CNS).
Seizures in the neonate
In cases of neonatal seizures an underlying cause can be found in 75 to 90%.(19) There are many causes for seizures in neonates but hypoxic ischaemic encephalopathy (HIE), intracranial haemorrhage, intracranial infection and developmental defects account for up to 85% of neonatal seizures. ... Management of Atypical Genitalia & Suspected DSD in ...
Neonatal Seizures and Neonatal Syndromes
Neonatal seizures or neonatal convulsions are epileptic fits occurring from birth to the end of the neonatal period. 1-18 The neonatal period is the most vulnerable of all periods of life for developing seizures, particularly in the first 1-2 days to the first week from birth. They may be short-lived events lasting for a few days only.
Neonatal Seizures
Neonatal seizures (NS) result from rapid depolarization of brain cells that leads to excessive synchronous electrical activity. The brain cells of a newborn are immature and vulnerable to insults. Therefore, NS often indicate an underlying neurologic disturbance. They require immediate assessment to determine the underlying cause and necessary interventions. Recurrent seizures have been found ...
Neonatal seizures after pyridoxine use
1. Neonatal seizures after use of pyridoxine in pregnancy. 2. Apparent response of impaired mental development, minor motor epilepsy and ataxia to pyridoxine. 3. Atypical presentations of pyridoxine dependent seizures: a treatable cause of intractable epilepsy in infants. 4.
Neonatal Seizures: An Overview of Genetic Causes and Treatment Options
2. Epileptogenesis in the Neonatal Brain. Epileptogenesis is a process through which a wide variety of causes (genetic, structural, metabolic, etc.,) may determine changes in the neuronal tissue, leading to the generation of unprovoked seizures or their progression after the epileptic condition has been established [5,15].This process occurs during the early stages of life, hence, in newborns ...
Neonatal seizures associated with a severe neonatal myoclonus like
We report a mother and son with an atypical presentation of familial neonatal epilepsy. The mother has persistent epilepsy and subnormal intelligence. The son developed a severe dyskinesia clinically compatible with multifocal myoclonus in the neonatal period that only responded to carbamazepine. He also has ataxia and delayed psychomotor ...
Congenital mixed hiatal hernia: A case report of an atypical cause of
Treatment recommendations are based upon the type of hernia and clinical presentation (detailed in Table 1). Congenital mixed hiatal hernia is a complex clinical scenario. Diagnosis and management of this condition in neonates remain intricate endeavors due to its rarity and variable clinical presentations.
JCM
Drug-induced or associated vasculitis is a prevalent form of vasculitis that resembles primary idiopathic antineutrophil cytoplasmic autoantibody (ANCA) vasculitis (AAV). Cocaine is a diffuse psychostimulant drug and levamisole is a synthetic compound used to cut cocaine. Their abuse may result in a spectrum of autoimmune manifestations which could be categorized into three overlapping ...
Genetic diagnosis of neonatal-onset seizures
The clinical manifestations of neonatal seizures are atypical and the etiology is complex. This study demonstrates that most of seizures with unexplained causes in the neonatal period were due to epilepsy (13/15). Epileptic seizures are common 3 days after birth with frequent episodes at the beginning of the disease.
Term Neonate with Atypical Hypoxic-Ischemic Encephalopathy Presentation
2 Atypical presentations have been associated with inborn errors of metabolism (urea cycle disorders, organic and amino acid disorders, glutaric aciduria) or meningitis. All were screened for and ruled out in our patient. ... Gillam-Krakauer M, Carter B S. Neonatal hypoxia and seizures Pediatr Rev 2012 33 09 387-396., quiz 397 [Google Scholar] 2.