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An event is serious (based on the ICH definition) when the patient outcome is:
* congenital anomaly
* other medically important event
In a case report, 3 neonates [two boys and one girl; exact ages not stated] were described, who exhibited lack of efficacy during treatment with dopamine, epinephrine or pyridoxine [not all routes and dosages stated].
Case 1: A male neonate born at 304/7 weeks of gestational age with a birth weight of 2100g. He was admitted to the NICU, in Italy with immediate onset of noninvasive ventilatory support; however, due to worsening of respiratory conditions, he was intubated and treated with surfactant. At 3 days old, seizures occurred characterised by clonic jerks at the lower right limb, often spreading to the right hand and to the counter-lateral limbs, recurring at least 1–2 times/h and lasting for about 1 minute. Interictal neurological examination showed severe diffuse hypotonia and extremely poor general movements. Following investigations, neonatal status epilepticus was considered and he initially received levetiracetam. However, only a partial reduction of seizures was observed. It was continued with a levetiracetam maintenance dose, and a bolus of pyridoxine 100 mg/day was administered. As the seizure persisted phenobarbital was administered with transient seizure disappearance; however, they relapsed. He was also administered with midazolam, but showed poor results. Sleeping EEGs were serially performed and revealed persistence of electric seizures without relevant clinical manifestations. Brain MRI scan revealed eccentric venous thrombosis, for which he received unspecified low-molecular-weight heparin with associated folic acid supplementation. Treatment with levetiracetam was continued, but pyridoxine was suspended due to lack of efficacy. Later, he received hydrocortisone, and the electrical seizure were disappeared after 2 days. Subsequently, interictal EEG abnormalities also disappeared. Later, hydrocortisone was down titrated and midazolam was withdrawn gradually. At discharge, he was seizure free and a slight improvement in axial tone was noticed at neurological examination. On a follow-up, no recurrence of seizure was noted and levetiracetam was down titrated. At further visit, he remained seizure free. The EEG showed background activity mainly characterised by medium–low-voltage theta rhythms, and a further brain MRI scan was found to be normal. Levetiracetam was withdrawn.
Case 2: A female neonate born at 404/7 weeks of gestation with a birth weight of 2100g. On the 3rd day of life, she presented with focal seizures mainly characterised by lateralised tonic posturing and flushing, followed by clonic jerks at the same side, and later shifting to the contralateral side, associated with perioral cyanosis and sweating lasting for almost 30–50 sec, and recurring many times a day. Family history was negative for epilepsy and other neuropsychiatric disorders. Following investigations, neonatal status epilepticus was considered and she was admitted to the NICU, in Italy . She initially received levetiracetam with transient benefit. Her treatment was followed with oral pyridoxine 100mg, but it showed no benefits. Also, administration of midazolam leads to reduction of seizures but persistence of the interictal discharges. On the 9th day of life, a sleeping EEG showed the presence of electroclinical episodes with slight motor and dysautonomic phenomenology. The interictal EEG showed focal discharges shifting from one side to the other. Levetiracetam dose was increased, and phenobarbital was administered with a transient reduction of seizures, but it was relapsed. On the 10th day of life, therapy with hydrocortisone was initiated, and the seizures disappeared after 24 hour. The EEG showed gradual disappearance of the abnormal discharges. A gradual withdrawal of midazolam was performed, and on the 21st day of life, hydrocortisone was gradually decreased and subsequently withdrawn on the 29th day of life. Further, next-generation sequencing showed the presence of a de novo heterozygous mutation in the KCNQ2 gene (c.2555delC (p.Pro852Argfs*78)). At the 6-month follow-up, the EEG showed high-voltage theta frequencies with sporadic rapid activity in the frontal regions. Treatment with levetiracetam was continued and she was seizure-free.
Case 3: A male neonate was born at the 324/7 weeks of gestation with a birth weight of 1760g. On the 1st day of life, due to the appearance of left pneumothorax, thoracic drainage was positioned and he was admitted to the NICU, in Italy. Noninvasive ventilatory support was maintained with subsequent treatment with surfactant. Thereafter, he was initiated on EV [sic] dopamine and epinephrine [adrenaline]. However, his condition worsened leading to intubation. Later on day 16, he developed recurrent seizures, and neonatal status epilepticus was considered for which he received levetiracetam and midazolam. Subsequently, he received hydrocortisone, and all his symptoms subsided after 2 days. Laboratory tests were found to be normal.
Di Rosa G, et al. Efficacy of intravenous hydrocortisone treatment in refractory neonatal seizures: A report on three cases. Brain Sciences 10: 1-12, No. 11, 20 Nov 2020. Available from: URL: http://doi.org/10.3390/brainsci10110885