Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures.

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.

22q11.2 deletion syndrome lowers seizure threshold in adult patients without epilepsy.

OBJECTIVE: Previous studies examining seizures in patients with 22q11.2 deletion syndrome (22q11.2DS) have focused primarily on children and adolescents. In this study we investigated the prevalence and characteristics of seizures and epilepsy in an adult 22q11.2DS population. METHODS: The medical records of 202 adult patients with 22q11.2DS were retrospectively reviewed for documentation of seizures, electroencephalography (EEG) reports, and magnetic resonance imaging (MRI) findings. Epilepsy status was assigned in accordance with 2010 International League Against Epilepsy Classification. RESULTS: Of 202 patients, 32 (15.8%) had a documented history of seizure. Of these 32, 23 (71.8%) had acute symptomatic seizures, usually associated with hypocalcemia and/or antipsychotic or antidepressant use. Nine patients (9/32, 28%; 9/202, 4%) met diagnostic criteria for epilepsy. Two patients had genetic generalized epilepsy; two patients had focal seizures of unknown etiology; two had epilepsy due to malformations of cortical development; in two the epilepsy was due to acquired structural changes; and in one patient the epilepsy could not be further classified. SIGNIFICANCE: Similarly to children, the prevalence of epilepsy and acute symptomatic seizures in adults with 22q11.2DS is higher than in the general population. Hypocalcemia continues to be a risk factor for adults, but differently from kids, the main cause of seizures in adults with 22q11.2DS is exposure to antipsychotics and antidepressants. Further prospective studies are warranted to investigate how 22q11.2 microdeletion leads to an overall decreased seizure threshold.

Traumatic lingual hematoma after generalized tonic-clonic seizure in a patient with an acquired coagulopathy.

Oral lacerations are common complications of seizures and account for 92% of all oral injuries. Seizures are relatively commonly associated with chronic alcohol consumption. It is already known that provoked seizures can occur after a sudden cessation of prolonged alcohol intoxication. Meanwhile, chronic alcohol consumption can disrupt the blood coagulation process on several levels. This report aims to present a case of generalized tonic-clonic seizure in a man with chronic alcoholism and acquired coagulopathy who suffered severe tongue injury during a seizure. A 45-year-old man was brought to the emergency department after a first-in-life generalized tonic-clonic seizure. He gave information that he bit his tongue during the seizure. Shortly afterward, the patient had another generalized seizure during which he stopped breathing and was intubated. On admission, the patient was sedated, intubated, and on mechanical ventilation, with no signs of focal neurological deficit. A detailed physical examination revealed massive tongue swelling, which was significantly moved forward. Laboratory tests revealed coagulopathy (INR 2,10) severe thrombocytopenia with a platelet count of 50x109/L. Electrolyte values were in the reference range. According to the maxillofacial surgeon's recommendation, he was treated conservatively, and after 2 weeks, he was clinically stable with a significant reduction of lingual hematoma and without new epileptic events. In our case, decreased platelet count and probable platelet dysfunction associated with chronic alcohol consumption and tongue bite during generalized tonic-clonic seizure played a significant role in developing lingual hematoma. These fast-developing lingual hematomas can lead to possible airway obstruction; therefore, careful observation and timely intubation are mandatory to prevent possible fatal complications.

Seizures Provoked by Greasy Pork in a Patient With Refractory Focal Epilepsy.

Seizures have been reported to be directly triggered by certain foods in some people with epilepsy. On the other hand, eating epilepsy has been mentioned in the literature as a rare disorder characterized by clinical and EEG findings that vary from patient to patient and are interestingly prevalent in certain geographic areas. Epilepsy in these patients is either idiopathic or due to underlying brain pathology. We present a case of refractory focal epilepsy in which the patient reports seizures provoked by eating greasy pork. During the admission to the epilepsy monitoring unit (EMU), the patient did not have seizures during the first three days of the admission despite antiepileptic medication withdrawal, sleep deprivation, and photic stimulation. However, when he consumed greasy pork, he had tonic-clonic convulsions about five hours after eating. On the following day, he had another tonic-clonic seizure after eating greasy pork.

A novel approach to seizures in neonates.

THE CHALLENGE OF SEIZURE RECOGNITION: Recognition of seizures in neonates remains the foremost challenge to overcome. All neonates at risk for seizures, especially the critically ill, should undergo video-EEG monitoring. The initial step toward an accurate diagnosis is the accurate description and interpretation of the electro-clinical phenotype. THE IMPORTANCE OF SEIZURE SEMIOLOGY AND ASSOCIATION WITH ETIOLOGY: The early distinction between acute provoked seizures and neonatal-onset epilepsies serves as the primary determinant for guiding management, treatment choices, and duration. Seizures in neonates should be seen as a symptom, not a disease, and their semiology may suggest the etiology. TREATMENT OF ACUTE PROVOKED SEIZURES: Neonates with hypoxic-ischemic encephalopathy respond best to phenobarbital, while levetiracetam is a better choice for neonates with congenital heart diseases. Anti-seizure medication can be discontinued after 72 h of seizure freedom, before discharge from the hospital. TREATMENT OF NEONATAL EPILEPSIES: Neonates with epilepsy usually require a personalized, etiology-based approach in terms of choice and duration of treatment. Neonates with channelopathies tend to respond to sodium channel blockers such as carbamazepine, oxcarbazepine, or phenytoin. The surgical option should be considered early in cases of large brain malformations, such as hemimegalencephaly.

Provoked seizures at the onset of progressive disease contribute to diagnosis delay - A tertiary center experience in a cohort of 22 children with CLN2.

PURPOSE: The evaluation of epilepsy features and factors with impact to diagnosis delay in children with CLN2. METHOD: The study included children with CLN2 treated from 2000 to 2020. Diagnosis was confirmed by: TPP1 deficiency and/or TPP1 gene mutation or pathognomonic electron microscopy findings. The seizure features were evaluated: the age of onset, provocation, semiology and EEG. The disease severity was assessed by CLN2 Clinical Rating Scale (CLN2-CRS). Statistical analysis included T test, chi-square test, Wilcoxon-Mann-Whitney test, using SPSS statistics 25. RESULT: The study included 22 children with CLN2. Seizures were experienced by all cases at the early stage of disease, preceded by language delay in 18, and behavior problems in 14 pts. The first seizure was provoked in 9 children at mean age of 33.8 ± 4.6 months, and unprovoked in 13 at mean age of 34.6 ± 2.7 months. In patients with provoked first seizure, the average period from the first seizure to diagnosis was longer (35.1 months), with lower CLN2-CRS, then in those with unprovoked (23.8 months) first seizures (p < 0.008). Initial seizures were generalized tonic-clonic (Pampiglione and Harden, 1973 Feb) [8], atonic (Pampiglione and Harden, 1973 Feb) [8], and focal (Beltrán et al., 2018 Aug) [4], with recurrence within two months. With progression, the patients experienced multiple seizure types, and 1/3 suffered status epilepticus. CONCLUSIONS: Provoked seizures at the onset of CLN2 have impact to diagnosis delay. The red flags are: preceding language delay and behavior problems, later FS onset comparing to the typical age, atonic, focal and long-lasting seizure, and recurrence of seizures within two months.

Acute symptomatic seizures: an educational, evidence-based review.

Acute symptomatic seizures occurring in close temporal relationship with an acute CNS insult are distinct from epilepsy and occur frequently in clinical practice. The aim of this educational review is to provide information on the most important aspects related to acute symptomatic seizures that will allow clinicians to accurately distinguish acute symptomatic seizures from epilepsy in their patients. We explain the definition of acute symptomatic seizures and we illustrate how acute symptomatic seizures differ from epilepsy. We describe acute symptomatic seizures in the context of their various underlying aetiologies and we discuss the approach to the management of patients with acute symptomatic seizures.

Acute symptomatic seizures and hippocampal sclerosis: the major contributor for post-stroke epilepsy?

OBJECTIVE: Hippocampal sclerosis (HS) is a prominent biomarker of epilepsy. If acquired later in life, it usually occurs in the context of degenerative or acute inflammatory-infectious disease. Conversely, acute symptomatic seizures (ASS) are considered a risk factor for developing post-stroke epilepsy, but other factors remain unrecognized. Here, we hypothesize that silent hippocampal injury contributes to the development of post-stroke epilepsy. METHODS: We performed a retrospective observational study of patients hospitalized between 1/2007 and 12/2018 with an acute stroke in the Stroke Center of the Geneva University Hospital. Patients were included if they had a documented normal hippocampal complex at onset and a control MRI at ≥ 2 year interval without new lesion in the meantime. RESULTS: 162 patients fulfilled our inclusion criteria. ASS during the first week (p < 0.0001) and epileptiform abnormalities in electroencephalography (EEG; p = 0.02) were more frequently associated with the development of epilepsy. Hemorrhagic stroke was strongly associated to both ASS and future focal epilepsy (p = 0.00097). Three patients (1.8%) developed hippocampal sclerosis ipsilateral to the cerebrovascular event between 2 and 5 years, all with ASS and hemorrhagic stroke. INTERPRETATION: ASS and epileptiform EEG abnormalities are strong predictors of post-stroke epilepsy. HS develops in a minority of patients after hemorrhagic lesions, leading to focal epilepsy. Prospective studies are required, including follow-up with EEG and if characterized by epileptiform discharges, with MRI, to determine the true frequency of HS and to better understand predictors of post-stroke epilepsy (AAS, stroke type, and HS), and their impact on stroke recovery.

Seizures in the neonate: A review of etiologies and outcomes.

Neonatal seizures occur in their majority in close temporal relation to an acute brain injury or systemic insult, and are accordingly defined as acute symptomatic or provoked seizures. However less frequently, unprovoked seizures may also present in the neonatal period as secondary to structural brain abnormalities, thus corresponding to structural epilepsies, or to genetic conditions, thus corresponding to genetic epilepsies. Unprovoked neonatal seizures should be thus considered as the clinical manifestation of early onset structural or genetic epilepsies that often have the characteristics of early onset epileptic encephalopathies. In this review, we address the conundrum of neonatal seizures including acute symptomatic, remote symptomatic, provoked, and unprovoked seizures, evolving to post-neonatal epilepsies, and neonatal onset epilepsies. The different clinical scenarios involving neonatal seizures, each with their distinct post-neonatal evolution are presented. The structural and functional impact of neonatal seizures on brain development and the concept of secondary epileptogenesis, with or without a following latent period after the acute seizures, are addressed. Finally, we underline the need for an early differential diagnosis between an acute symptomatic seizure and an unprovoked seizure, since it is associated with fundamental differences in clinical evolution. These are crucial aspects for neonatal management, counselling and prognostication. In view of the above aspects, we provide an outlook on future strategies and potential lines of research in this field.

Clinico-laboratory characteristics and outcome of patients with eucalyptus oil-induced/provoked seizures: A case series and systematic review of the published patients.

Seizures triggered by skin application, inhalation or ingestion of over-the-counter medications containing eucalyptus oil are known. We report five children who suffered likewise. We made a systematic search for all reported cases and performed a pooled analysis to provide a comprehensive estimate of the type of seizures, their management and outcome. In 110 cases (49 children), inhalational use was the most predominant, generalised tonic-clonic (the commonest semiology) and levetiracetam was the most common anti-convulsant treatment used. Most cases had an uneventful recovery. Adults were less likely to have prolonged and multiple seizures, requiring intensive care or mechanical ventilation.

Acute Symptomatic Seizures and Provoked Seizures: to Treat or Not to Treat?

PURPOSE OF REVIEW: Acute symptomatic and provoked seizures by definition occur in close proximity to an event and are considered to be situational. The treatment implications and likelihood of recurrence of acute symptomatic and provoked seizures differ from unprovoked seizures. In this article, the authors review the literature on acute symptomatic and provoked seizures with regard to therapeutic approach and risk of recurrence. RECENT FINDINGS: In the acute period, patients who suffer from acute symptomatic and provoked seizures have higher rates of morbidity and mortality. Patients with acute symptomatic seizures in the setting of certain conditions including subdural hemorrhage, traumatic penetrating injuries, cortical strokes, neurocysticercosis, venous sinus thrombosis, and viral encephalitis have a higher rate of seizure recurrence although the rate of recurrence of seizures is less than that of patients with unprovoked seizures. In patients with acute symptomatic and provoked seizures, short-term treatment with anti-seizure medications is appropriate given the higher morbidity and mortality in the acute phase of illness. In patients with acute symptomatic seizures with persistent epileptiform activity on EEG and structural changes on imaging, longer-term treatment (i.e., a few months as opposed to 1 week) with anti-seizure medications can be considered due to high risk of seizure recurrence. If a patient subsequently has an unprovoked seizure, there is yet a higher risk of recurrence of seizures and likelihood of the development of epilepsy. In these patients, long-term seizure treatment can be considered, keeping in mind that although anti-seizure treatment may reduce risk of seizure recurrence in the short-term, it does not appear to influence long-term seizure remission rates.

Acute Symptomatic Seizures in Geriatric Patients with Multiple Risk Factors - A Diagnostic Challenge.

BACKGROUND: Acute symptomatic seizures and epileptic disorders are frequent health problems of elderly patients. An early and reliable distinction of the seizure etiology is important to ensure adequate treatment, and to prevent unwarranted diagnostic and therapeutic procedures. METHODS: We review the current literature based on a MEDLINE search, describe age-related problems in detail, with particular attention to clinical practice, discuss possible criteria and potential pitfalls for diagnostics, and provide a compilation of etiologic factors for acute symptomatic seizures. RESULTS: The most common causes of acute symptomatic seizures - acute cerebrovascular disorders, metabolic disorders, traumatic brain injury, meningo-encephalitis, cerebral tumors, and withdrawal of alcohol and other central agents - are well-defined and seem to permit straightforward diagnostic and therapeutic strategies. The current classification of seizures and epileptic syndromes apparently provides clear definitions. However, multiple age-related risk factors, as well as a reduced discriminatory power of clinical and technical diagnostic criteria can make the distinction difficult. CONCLUSION: Typical age-related problems are incomplete or missing medical history, dementia, oligosymptomatic seizures, inconclusive EEG and cerebral imaging results, multiple pathological findings and comorbidity with ambiguous significance, confounding sleep disorders, intake of proconvulsive drugs, and psychogenic seizures. All diagnostic and therapeutic decisions need to be based on an integrative and individual approach that includes diagnostic findings and risk factors, the intake of medications and other agents, and the social situation of the elderly patient.

Noninvasive treatment alternative for intractable startle epilepsy.

We describe a treatment alternative for intractable, startle-provoked, epileptic seizures in four children aged between 8 and 14. Three of the four children had symptomatic localization-related epilepsy. They all suffered from intractable epilepsy precipitated by sudden sounds. The fact that seizures tended to occur with high frequency - more than one seizure a day - had a clear impact on daily life. Clinical seizure pattern demonstrated asymmetric tonic posturing in all four children. Three children experienced several seizure types including focal seizure onset. All children had focal neurological signs or learning disabilities or a combination of both. Our noninvasive treatment method using psychoeducational counseling and sound generators was applied in four children, resulting in a seizure frequency reduction of ≥ 50% in two of them.