Cardiac arrhythmias in neonates receiving lidocaine as anticonvulsive treatment

Lidocaine has been used in neonates as an effective drug in controlling neonatal seizures not responding to traditional anticonvulsant therapy. Little is known about the effect of lidocaine on heart rate or occurrence of cardiac arrhythmias in neonates. The purpose of the present study was to assess the incidence of cardiac arrhythmias associated with lidocaine use for neonatal seizures. A retrospective review was performed in 207 neonates who received lidocaine for treatment of neonatal seizures. All were given a loading dose of 2 mg/kg in 10 min followed by a continuous infusion of 6 mg/kg per h, tailed off over the next 48 h. A total of ten (4,8%) infants developed cardiac arrhythmias during lidocaine infusion. In five infants a bradycardia developed, associated with a prolonged QRS complex in one. In one infant a tachycardia was seen following the bolus administration. In the other four an irregular heart rate was noted. In eight infants the arrhythmias disappeared immediately following discontinuation of lidocaine. In two infants, with severe encephalopathy, who died, the association was not so clear. Conclusion:The present study demonstrates that continuous cardiac monitoring of neonates who receive lidocaine for neonatal seizures is indicated, as there is a risk to develop cardiac arrhythmias. Lidocaine should be discontinued immediately when a cardiac arrhythmia occurs. Lidocaine should not be given to patients with a congenital heart disease and to infants who have already been treated with diphantoine.     

Clinico-etiological and EEG profile of neonatal seizures

Objective To evaluate clinical, etiological and EEG profile of neonatal seizures. Methods In all the neonates enrolled in the study baseline information recorded was sex, gestational age, weight, ponderal index etc. Clinical profile of seizure episode included age at onset of seizure, type and duration of seizure, associated autonomic changes, medication given, response time to medication and possible cause. Relevant maternal history including antenatal and peripartum history was recorded. Relevant history and examination of newborn were noted. Essential investigations done in all subjects included blood glucose, serum calcium, serum sodium and arterial pH. USG cranium and EEG were done at earliest in all the subjects wherever feasible. Additional investigations were done as guided by history, physical examination and essential investigations. Results Ninety babies with clinical seizures were enrolled into the study over one year period with an overall incidence of 1.17% (0.69% in term babies and 6.14% in preterm babies). Abnormal EEG’s were found in one third cases out of 60 EEG’s done in 90 babies. 26.7% of babies with perinatal asphyxia had abnormal EEG’s (8/30). While 60% of babies with HIE II had abnormal discharges, background activity was suppressed in 66.66% EEG’s in babies with HIE III. Conclusions Overall incidence of neonatal seizures was 11.7/1000 live births, majority being preterm very low birth weight babies before 5 days of life. Perinatal asphyxia was responsible in 44.44% babies followed by metabolic abnormalities (23.33%). EEG abnormalities were present in 33.34% babies.     

Hypophosphatasia as a rare cause of neonatal seizures

Severe forms of hypophosphatasia due to loss-of-function in the ALPL gene may present with diverse neurological problems including pyridoxine-responsive seizures. We present a short report of pyridoxine-responsive neonatal seizures. Due to severe osteopenia with unmeasurable levels of alkaline phosphatase, targeted genetic screening was performed and two pathogenic variants in the gene for the nonspecific alkaline phosphatase confirmed the diagnosis of hypophosphatasia. We would like to emphasize the importance of considering infantile hypophosphatasia in the differential diagnosis of pyridoxine-responsive seizures with concomitant low alkaline phosphatase level and bone pathology, especially with the new treatments becoming available in the future.     

A study of phenobarbital and dilantin in neonatal seizures

A total of 40 cases of neonatal convulsions of different nonmetabolic aetiological factors were studied. Patients with kernicterus were included in the study. Peak plasma phenobartibal concentrations after incremental loading doses of phenobarbital i.e. 10 mg/kg, 15 mg/kg, and 20 mg/kg were determined. Diphenylhydantoin was added if phenobarbital alone was unable to control seizures. In three patients, a combination of phenobarbital and diphenylhydantoin was used as the initial loading therapy. Increase in the loading dose of phenobarbital was associated with an increase in its peak plasma concentration. Despite increase in the plasma phenobarbital concentration beyond the ‘therapeutic’ levels suggested by the Western studies, doses of 15 mg/kg and 20 mg/kg of phenobarbital were unable to score over the traditional regimen of 10 mg/kg. Convulsions were controlled in 50% of the patients with any of these three regimens, irrespective of the aetiology. Convulsions were controlled in 7 out of the 9 cases where diphenylhydantoin was added, because of the failure of phenobarbital in controlling the convulsions as a single drug. Convulsions of all the three patients, in whom a combination of phenobarbital and diphenylhydantoin was used by random selection as the initial bolus, were controlled. Seizure effects were difficult to distinguish from drug effects but major side effects were not encountered despite the fluctuating drug levels in the sick neonate.     

An algorithm for the automatic detection of seizures in neonatal amplitude-integrated EEG

AIM: To develop and evaluate an algorithm for the automatic screening of electrographic neonatal seizures (ENS) in amplitude-integrated electroencephalography (aEEG) signals. METHODS: CFM recordings were recorded in asphyxiated (near)term newborns. ENS of at least 60 sec were detected based on their characteristic pattern in the aEEG signal, an increase of its lower boundary. The algorithm was trained using five CFM recordings (training set) annotated by a neurophysiologist, observer1. The evaluation of the algorithm was based on eight different CFM recordings annotated by observer1 (test set observer 1) and an independent neurophysiologist, observer2 (test set observer 2). RESULTS: The interobserver agreement between observer1 and 2 in interpreting ENS from the CFM recordings was high (G coefficient: 0.82). After dividing the eight CFM recordings into 1-min segments and classification in ENS or non-ENS, the intraclass correlation coefficient showed high correlations of the algorithm with both test sets (respectively, 0.95 and 0.85 with observer1 and 2). The algorithm showed in five recordings a sensitivity > or = 90% and approximately 1 false positive ENS per hour. However, the algorithm showed in three recordings much lower sensitivities: one recording showed ENSs of extremely high amplitude that were incorrectly classified by the algorithm as artefacts and two recordings suffered from low interobserver agreement. CONCLUSION: This study shows the feasibility of automatic ENS screening based on aEEG signals and may facilitate in the bed-side interpretation of aEEG signals in clinical practice.     

Clinical features of neonatal seizures

Objectives: Identification of seizures in neonates is difficult. This study analyses the clinical features of seizures in a cohort of neonates.
Methodology: The clinical events of 41 neonates referred for investigation of suspected seizures were studied with prolonged video/electroencephalographic (EEG) telemetry.
Results: Sixteen neonates had no seizures recorded; 25 had confirmed seizures, 13 with clinical correlates. Each neonate with electroclinical seizures had paroxysms of abnormal movements in stereotyped patterns. These patterns were consistently found to have electrical correlates. Focal clonic movements were seen most frequently. Multiple clinical features characterized the seizure repertoire in six neonates. In five neonates the clinical features became less evident during monitoring and these seizures were difficult to recognize. This change was associated with anticonvulsant administration in three cases.
Conclusions: Electroclinical seizures are characterized by abnormal paroxysmal stereotyped behaviour, often with multiple clinical features. Recommendations for the management of abnormal neonatal events are proposed.     

Acute symptomatic neonatal seizures in preterm neonates: etiologies and treatments

Acute symptomatic neonatal seizures in preterm newborns are a relevant clinical challenge due to the presence of many knowledge gaps. Etiology-wise, acute symptomatic seizures have an age-specific epidemiology, with intraventricular hemorrhage and its complications representing the first cause in extremely and very preterm neonates, whereas other etiologies have similar occurrence rates as in full-term infants. Specific treatment strategies for the premature neonates are not yet available. Studies suggest a similarly low response rate with even more unfavorable prognosis than in full-term infants. Pharmacodynamic and pharmacokinetic changes are likely under way during the preterm period, with the potential to affect both effectiveness and safety of antiepileptic drugs in these patients. However, due to the lack of clear evidence to guide prioritization of second-line drugs, off-label medications are frequently indicated by review papers and flow-charts, and are prescribed in clinical practice. We therefore conclude by exploring potential future lines of research.     

Punctate white matter lesions in full-term infants with neonatal seizures associated with SLC13A5 mutations

Introduction

Early-onset epileptic encephalopathy caused by biallelic SLC13A5 mutations is characterized by seizure onset in the first days of life, refractory epilepsy and developmental delay. Little detailed information about the brain MRI features is available in these patients.

Lidocaine for treatment of severe seizures in newborn infants. II. Blood concentrations of lidocaine and metabolites during intravenous infusion

The blood concentrations of lidocaine and its main active metabolites, methylethylglycinexylidide (MEGX) and glycinexylidide (GX), were measured in 24 newborn infants during anticonvulsive treatment with an iv infusion of lidocaine. After a bolus dose of 1.5-2.2 mg/kg and continuous infusion of lidocaine (4.7-6.3 mg/kg/h) there was accumulation of the drug and MEGX within 24 h. After termination of the iv infusion, both lidocaine and the metabolites were eliminated within 24-48 h. The anticonvulsive effectiveness--estimated by clinical observation and continuous amplitude integrated EEG monitoring (cerebral function monitor)--was immediate in 15 infants (nine term and six preterm). There was no correlation between blood concentrations of lidocaine and metabolites, and anticonvulsive effect (i.e. good, intermediate or no response). No differences in blood concentrations were found between full-term and preterm babies, or between infants with or without birth asphyxia. In combination with a fast withdrawal of the drug, few adverse reactions were seen with the dosages used, even though blood concentrations were high. Routine measurements of lidocaine concentrations during anticonvulsive treatment in neonates seem to be of little clinical value. For evaluation of the anticonvulsive effect and for early detection of seizure activity during lidocaine withdrawal, continuous EEG monitoring is preferable.     

Neonatal seizures: Aetiology by means of a standardized work-up

Neonatal seizures are an alarming symptom and are frequent in neonates. It is important to find the cause of neonatal seizures to start a specific treatment and to give a meaningful prognosis. The aim of this study is to investigate the incidence of different aetiologies of neonatal seizures in our hospital by a specific work-up.MethodsAll full-term born neonates from January 2002 till September 2009 with neonatal seizures, admitted to our neonatal intensive care unit were included (n = 221). Aetiology was investigated by means of a standardized aetiologic work-up.ResultsThe frequencies of aetiologies of neonatal seizures were: hypoxic-ischemic encephalopathy (HIE) (n = 119; 53.9%), metabolic or electrolyte disorders (n = 24; 10.9%), intracranial hemorrhage (n = 20; 9.0%), ischemic infarction (n = 16; 7.2%), intracranial infections (n = 14; 6.3%), congenital malformations of the central nervous system (n = 7; 3.2%), inborn errors of metabolism (n = 5; 2.3%), epileptic syndromes (n = 1; 0.5%), HIE + hypoglycemia (n = 4; 1.8%), HIE + intracranial hemorrhage (n = 3; 1.4%), HIE + ischemic infarction (n = 1; 0.5%), ischemic infarction + intracranial hemorrhage (n = 1; 0.5%), idiopathic (n = 4, 1.8%), intoxications (n = 1; 0.5%) and unknown (n = 1; 0.5%).ConclusionOur work-up is a practical tool to find the aetiology of neonatal seizures.     

A paradoxical rise of neonatal seizures after treatment with vitamin B6

We report the case of a newborn with intractable epileptic seizures developing a paradoxical rise of seizure frequency and electroencephalogram alterations after administration of vitamin B6. We have been unable to determine the aetiology of this disorder. In a newborn presenting with drug-resistant epileptic seizures, the first therapeutic option remains the application of intravenous pyridoxine, but the physician should be aware of the risk of an increase in seizure frequency.     

Severe digoxin intoxication in a child treated by infusion of digoxin-specific Fab-antibody-fragments

Accidental digitalis ingestion in children is a rare, but potentially life-threatening emergency.We report the case of a 210/12-year-old boy with accidental ingestion of 6 mg -Acetyl-digoxin. Soon after admission, the boy developed sinus bradycardia, SA and AV-block, of increasing severity without circulatory impairment. As the serum digoxin level reached 21.7 ng/ml digoxin-specific Fab-antibody-fragments were used to bind free serum digoxin. Immediately after infusion, serum free digoxin was below the detection limit, whereas total digoxin peaked at 219 ng/ml 5 h thereafter. The arrhytmias did not subside totally, so that in addition, a transvenous pacemaker was placed, but never used.The antibody-infusion was well tolerated and the boy was discharged in good health.     

Drug treatment of neonatal seizures by neonatologists and paediatric neurologists

OBJECTIVE: To survey anti-epileptic drug (AED) treatment of early-onset neonatal seizures by neonatologists and paediatric neurologists. METHODS: A self-administered questionnaire was posted to Australian and New Zealand neonatologists and paediatric neurologists. Participants were given the hypothetical case of a full-term infant with early-onset seizures following perinatal asphyxia and asked to nominate their preferred AED for treatment of three seizure episodes during the first 24 h. RESULTS: One hundred and seven (57%) of 187 individuals answered the questionnaire: neonatologists responded more often than neurologists (chi(2) (1,187) = 7.18, P = 0.007). Phenobarbitone was used by 95% of the respondents to treat the first episode of seizures and 75% of them used an appropriate loading dose (20 mg/kg). Phenobarbitone was used by 84 and 40% of the respondents to treat the second- and third-seizure episodes, respectively. Neonatologists used phenobarbitone, phenytoin and a benzodiazepine with equal frequency to treat a third episode of seizures, whereas neurologists rarely used a benzodiazepine. Neonatologists used significantly larger total doses of phenobarbitone than neurologists. Very few respondents used pyridoxine to treat recurrent seizures that were historically linked to perinatal asphyxia and hypoxic-ischaemic encephalopathy. Neonatologists were more likely than neurologists to discontinue AED within a few days of seizure cessation (chi(2) (1,106) = 11.60, P = 0.0006). CONCLUSIONS: Australian and New Zealand neonatologists and paediatric neurologists generally use phenobarbitone to treat neonatal seizures presumed to be owing to hypoxic-ischaemic encephalopathy, though they do not always use appropriate doses. Neonatologists use phenobarbitone, phenytoin or a benzodiazepine for second and third episodes of seizures, whereas neurologists tend not to use benzodiazepines. Neonatologists use larger total doses of phenobarbitone than neurologists in pursuit of seizure control. Neonatologists discontinue AED earlier than neurologists.     

Sturge–Weber syndrome without facial nevus: An unusual cause of neonatal seizures

Sturge‐Weber syndrome is a neurocutaneous syndrome characterised by facial port wine stain, ipsilateral leptomeningeal angioma and vascular eye abnormalities. We report a rare case of Sturge‐Weber syndrome without facial nevus presenting with neonatal seizures.