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CC BY 4.0 · International Journal of Epilepsy
DOI: 10.1055/s-0045-1813216
Case Report

Early Infantile Developmental and Epileptic Encephalopathy: A Catastrophic Complication of COVID-19-Associated Multisystem Inflammatory Syndrome in Neonates

Authors

  • Choudri Muzafar Paswal 

    1   Pediatric Neurology Unit, Department of Pediatrics, Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India

  • Chandana Bhagwat

    1   Pediatric Neurology Unit, Department of Pediatrics, Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India

  • Kapil Goyal

    2   Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

  • Sameer Vyas

    3   Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India

  • Renu Suthar

    1   Pediatric Neurology Unit, Department of Pediatrics, Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Abstract

Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. While children are commonly affected by MIS-C, reports have described MIS in neonates (MIS-N) following maternal coronavirus disease 2019 (COVID-19) infection. We describe a case of early infantile developmental and epileptic encephalopathy (EIDEE) secondary to MIS-N in a day 18 old neonate secondary to maternal COVID-19. A term-born male neonate with a history of maternal COVID-19 at 35 weeks of gestation presented on day 18 of life with seizures, encephalopathy, pneumonitis, transaminitis, and elevated inflammatory markers. Magnetic resonance imaging (MRI) brain showed extensive cortical laminar necrosis. He was managed for MIS-N with antiseizure medications, antibiotics, and intravenous immunoglobulin. COVID-19 reverse transcriptase-polymerase chain reaction was negative, and anti-COVID immunoglobulin G antibody was positive. Near continuous multifocal myoclonic seizures were associated with a suppression burst pattern in the EEG. Follow-up MRI showed cystic encephalomalacia and loss of periventricular white matter. The EIDEE remained drug refractory with poor neurological outcome in follow-up. Cytotoxin-mediated neuronal injury in MIS-N can lead to a catastrophic complication of EIDEE, resulting in drug-refractory epilepsy, microcephaly, and adverse neurological outcome.


Keywords

neonates - COVID-19 - encephalitis - multisystemic inflammatory syndrome - seizures - encephalopathy - cortical laminar necrosis - microcephaly - early infantile developmental and epileptic encephalopathy

Key Messages

  • MIS-N is a rare but serious neonatal complication of maternal SARS-CoV-2 infection, secondary to passive transplacental transfer of antibodies.

  • Neurological involvement in MIS-N can be profound, such as cortical laminar necrosis and diffuse white matter injury in the index case, leading to EIDEE and long-term neurodevelopmental consequences.

  • Prompt immunomodulatory therapy is crucial. Early administration of intravenous immunoglobulin (IVIG) and supportive care can help mitigate systemic inflammation, though neurological insult can have a lasting impact.


Introduction

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the largest pandemic of recent times, affecting all age groups. Children are thought to be less commonly and less severely affected with COVID-19.[1] However, a potential life-threatening multisystem inflammatory syndrome in children (MIS-C) was reported among previously healthy children temporally associated with SARS-CoV-2 exposure.[2] Subsequently, neonates with multisystemic inflammation secondary to maternal COVID-19 were also described.[3] We report a neonate with MIS (MIS-N) following maternal COVID-19 infection with profound neurological complications.


Case Report

An 18-day-old male neonate presented to our center with complaints of seizures and encephalopathy. The baby was born at 38 weeks of gestation, through lower segment cesarean section with a birth weight of 2.3 kg (at 3rd centile for age). APGAR scores were 8 and 9 at 5 and 10 minutes, respectively. Antenatally, the mother developed symptomatic COVID-19 at 35 weeks of gestation with positive nasopharyngeal reverse transcriptase–polymerase chain reaction (RT-PCR), and an ultrasound at 37 weeks of gestation showed fetal growth restriction.

The neonate developed respiratory distress by 5 hours, multiple episodes of seizures and encephalopathy by the first 24 hours of life, requiring intubation and mechanical ventilation. Investigation showed thrombocytopenia (platelet count: 40,000/µL) and elevated AST (74 U/L), gamma glutamyl transferase (1,558 U/L; normal < 50 U/L), C-reactive protein (CRP: 82 mg/L), and D-dimer levels (3,750 ng/mL). Lumbar cerebrospinal fluid (CSF) examination showed 2 cells, 39 mg/dL glucose and 34 mg/dL protein. Blood and CSF cultures were sterile. Echocardiography showed normal ejection fraction with a tiny patent ductus arteriosus. He received intravenous vancomycin, meropenem, and colistin for suspected sepsis, and phenobarbitone for seizure control.

Rapid antigen test for SARS-CoV-2 on day 2 and day 5 of life was negative. The SARS-CoV-2 RT-PCR was not performed due to limited availability. Serum antibodies against SARS-CoV-2, tested at the peripheral hospital on day 7, were positive. Cranial ultrasound showed presence of hyperechoic periventricular white matter and magnetic resonance imaging (MRI) brain on day 11 of life showed extensive cerebral cortical laminar necrosis and cytotoxic edema involving cerebral white matter ([Fig. 1A, B]). Given persistent encephalopathy, the baby was referred to our hospital on the 18th day of life.

Zoom
Fig. 1 MRI brain axial diffusion-weighted images (DWIs) at the level of lateral ventricles on day 11 of life showing extensive white matter involvement of bilateral cerebral hemisphere, corpus callosum genu and splenium, and anterior and posterior limb of internal capsule (A). Axial T1-weighted image showing hyperintensities involving the cerebral cortex with hypointense subcortical white matter suggestive of cortical laminar necrosis (B). Clinical photograph at day 18 of life, showing extensive cutaneous desquamation at the palmar and dorsal aspect of both hands (C, D). MRI brain axial T1- and T2-weighted images at 3-month follow-up showing extensive cystic encephalomalacia of the cerebral cortex with loss of periventricular white matter with sparing of basal ganglia (E, F).

At admission, the neonate had stable vitals. The baby was lethargic, had poor state-to-state variability, absent visual fixation, axial hypotonia, and exaggerated deep tendon reflexes. Head circumference was <3rd centile for age. Desquamation of the skin over the hands and feet was noted ([Fig. 1C, D]). SARS-CoV-2 RT-PCR at day 19 of life from nasal swab was negative. Further investigations revealed elevated inflammatory markers, including D-dimer (3,750 ng/mL; normal levels <1,500 ng/mL), CRP (77 mg/dL), serum ferritin (511 ng/mL; normal levels <200 ng/mL), and interleukin-6 (91.6 pg/mL, normal <6 pg/mL) levels. Serum anti-SARS-CoV-2 IgG (immunoglobulin G) antibodies were detected by Ortho-Clinical Diagnostics Vitros chemiluminescent immunoassay (CLIA; Rochester, New York, United States), and the levels were found to be elevated, with a signal-to-cutoff ratio of 11.03 (<1: nonreactive, ≥1: reactive) at day 19 of life, respectively. Maternal anti-SARS-CoV-2 IgG antibodies were 13.4 (<1: nonreactive, ≥1: reactive). A diagnosis of MIS-N secondary to antenatal COVID-19 exposure was considered. Cardiac echocardiography was normal with normal coronary artery diameters. For MIS-N, intravenous immunoglobulin was given at 2 g/kg over 48 hours. Subsequently, inflammatory markers reduced, gradually his activity improved, and he was initiated on breastfeeding. Frequent multifocal myoclonic seizures in the awake state were observed. Video electroencephalogram showed suppression burst pattern in sleep and awake state, and some of the bursts of spikes and polyspikes were time-locked with myoclonic seizures. Serum ammonia, lactate, tandem mass spectrometry, urinary gas chromatography, urine for sulphite oxidase, and TORCH serology were negative. He was discharged from the hospital on day 37 of life on levetiracetam.

The baby continued to have poor head growth, closed anterior fontanelle, sutural overriding, spasticity, poor visual fixation, and exaggerated startle. Follow-up MRI revealed extensive cystic encephalomalacia involving bilateral frontal, parietal, temporal, and occipital lobes with sparing of basal ganglia, cerebellum, and brainstem ([Fig. 1E, F]). The drug-refractory tonic and myoclonic seizures and suppression burst pattern in VEEG were suggestive of early infantile developmental and epileptic encephalopathy (EIDEE). The seizures were partially responsive to antiseizure medications (phenobarbitone, levetiracetam, valproate, clonazepam, topiramate, zonisamide), and evolved to infantile epileptic spasm syndrome and with continued multifocal myoclonus. At 2 years of age, the child had global developmental delay, with developmental age of <3 months in all sectors, gross motor function classification system (GMFCS) of level 5, with significant feeding issue and persisting drug refractory epilepsy.


Discussion

MIS-N is a rare yet serious complication of maternal SARS-CoV-2 infection. Pathogenesis involves either transplacental transfer of maternal anti-SARS-CoV-2 antibodies leading to immune dysregulation or possible vertical transmission of the virus.[4] Among neonates with MIS-N, multiorgan dysfunction develops between day 1 and day 5 of life, and the most affected systems are cardiac, respiratory, and hematological systems,[3] followed by gastrointestinal and neurological involvement. Fever was reported in approximately 10% of neonates with MIS-N. Anti-SARS-CoV-2 IgM antibodies were negative among neonates with MIS-N, and 85% had positive IgG antibodies.[4] [5] [6]

The presence of pneumonitis, encephalitis, thrombocytopenia, and elevated inflammatory markers from day 1 of life, with the presence of anti-spike protein IgG antibodies in the serum at day 7 and 19 of life, suggested passive transfer of maternal anti-COVID-19 antibodies. Later in the course, development of cutaneous desquamation also supported the diagnosis of MIS-N.

Stroke, encephalitis, encephalopathy, Guillain–Barré syndrome, and acute disseminated encephalomyelitis are the most common neurological complications reported among children with COVID-19. Among these, approximately 40% cases were of MIS-C with neurological complications.[7] White matter hyperintensities and diffusion restriction in the corpus callosum splenium in patients with MIS-C. Either neurotropism of the SARS-CoV-2 virus or the secondary effects of systemic inflammatory responses, including post-viral autoimmune activation and hypercoagulability, may contribute to the neurological manifestations in MIS-C and MIS-N.[8]

Presence of neonatal seizures and encephalopathy in the index case in the presence of normal APGAR scores favors cytotoxin-mediated neuronal and white matter injury. The evolution from cortical laminar necrosis to cystic encephalomalacia and progressive microcephaly reflects the severity of the insult. Seizures and neonatal encephalopathy were reported in a day 22-old neonate following antenatal maternal COVID-19. Kumar et al report a case of acute cerebellitis as a rare complication of MIS-C in an 11-year old.[10] In a systematic review reporting 104 neonates with MIS-N, 25% had neurological complications, including encephalopathy and seizures. Neurological complications were more frequent in neonates with late-onset MIS-N, defined as the onset of symptoms after day 3 of life.[11] Acute encephalitis with cytotoxic edema involving the corpus callosum and bilateral centrum semiovale with diffusion restriction has been described with COVID-19 infection.[12] [13] Gomes et al reported autopsy findings in a 14-month-old girl with COVID-19 pneumonitis, and reported severe brain atrophy, cortical laminar necrosis, spongiosis, microvascular proliferation, and diffuse white matter edema. Immunostaining for SARS-CoV-2 spike protein was positive on choroid plexus and ependymal cells.[14] The short-term outcome of MIS-N is reported favorably, with no persistent long-term complications. However, long-term outcomes of MIS-N with neurological complications are not known. Evolution of EIDEE in the index case adds to the potentially devastating complications of neonatal MIS-N.

To conclude, MIS-N is a rare but very serious complication of maternal COVID-19 or SARS-CoV-2 exposure. Neurological complications of COVID-19 or MIS-N can be devastating in presence of extensive cortical laminar necrosis. EIDEE can be a rare but catastrophic complication of MIS-N.



Conflict of Interest

None declared.

Consent

Informed consent has been obtained from the patient party.



Address for correspondence

Renu Suthar, MD, DM
Pediatric Neurology Unit, Department of Pediatrics, PGIMER
Chandigarh 160012
India   

Publication History

Article published online:
20 January 2026

© 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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Zoom
Fig. 1 MRI brain axial diffusion-weighted images (DWIs) at the level of lateral ventricles on day 11 of life showing extensive white matter involvement of bilateral cerebral hemisphere, corpus callosum genu and splenium, and anterior and posterior limb of internal capsule (A). Axial T1-weighted image showing hyperintensities involving the cerebral cortex with hypointense subcortical white matter suggestive of cortical laminar necrosis (B). Clinical photograph at day 18 of life, showing extensive cutaneous desquamation at the palmar and dorsal aspect of both hands (C, D). MRI brain axial T1- and T2-weighted images at 3-month follow-up showing extensive cystic encephalomalacia of the cerebral cortex with loss of periventricular white matter with sparing of basal ganglia (E, F).