EEG and clinical characteristics of neonatal parechovirus encephalitis.

RATIONALE: Human parechoviruses (HPeVs) are single -stranded ribonucleic (RNA) viruses belonging to the picornaviridae family with characteristics similar to enteroviruses. They either cause mild respiratory and gastrointestinal or no symptoms in older children and adults but can be a major cause of central nervous system (CNS) infection in the neonatal period and demonstrate a seasonal predilection. Starting in March 2022, we saw eight patients with polymerase chain reaction (PCR) proven HPeV encephalitis with seizures and some electroencephalographic (EEG) features raising concerns for neonatal genetic epilepsy. Although cerebrospinal fluid (CSF) and imaging findings have been previously described, there is little emphasis on seizure presentation and EEG findings of HPeV in the literature. We wish to highlight the EEG and seizure semiology of HPeV encephalitis that may mimic a genetic neonatal epilepsy syndrome. METHODS: Retrospective chart review of all neonates seen at Children's Health Dallas, UTSW Medical Center between 03/18/2022-06/01/2022 with HPeV encephalitis. RESULTS: Term neonates (postmenstrual age 37-40 weeks) presented with a variable combination of fever, lethargy, irritability, poor oral intake, erythematous rash, and focal seizures. One patient with a single episode of limpness and pallor did not undergo EEG due to a low suspicion for seizures. CSF indices were normal in all patients. EEG was abnormal in all patients where performed (n = 7). EEG features included dysmaturity (7/7, 100 %); excessive discontinuity (6/7, 86 %); excessive asynchrony (6/7, 86 %); multifocal sharp transients (7/7, 100 %). Focal/multifocal seizures were captured in 6/7 (86 %); tonic in 3/7 (42 %) and described as migrating in 2 patients. Subclinical seizures were noted in 6/7 (86 %) with status epilepticus in 5/7 (71 %) patients. In 2/7 (28 %) the EEG showed a burst suppression pattern with poor state variation and voltages of < 5-10 uV/mm during the inter-burst intervals. Repeat EEG (3-11 days post initial EEG) showed improvement in 3 of 4 patients. No patient had ongoing seizures beyond day two of admission (22.5 h after EEG initiation). MRI showed extensive restricted diffusion in the supratentorial white matter, thalami, and less frequently the cortex, mimicking imaging findings of a metabolic or hypoxic-ischemic encephalopathy (7/8). Seizures responded within 36 h of presentation to treatment with acute bolus doses of medications. One patient died due to diffuse cerebral edema and status epilepticus. Six patients had a normal clinical exam at discharge. All patients started on maintenance antiseizure medication (ASM) were sent home on either a single medication or two medications (phenobarbital and levetiracetam) with plans to wean phenobarbital after discharge. CONCLUSIONS: HPeV is a rare cause of seizures and encephalopathy in neonates. Prior studies have emphasized specific patterns of white matter injury on imaging. We demonstrate that HPeV also commonly presents with clonic or tonic seizures with or without apnea and often subclinical multifocal and migrating focal seizures that could mimic a genetic neonatal epilepsy syndrome. Interictal EEG shows a dysmature background with excessive asynchrony, discontinuity, burst-suppression pattern, and multifocal sharp transients. However, we note that 100 % of patients responded quickly to standard ASM, and did not have seizures after hospital discharge- a factor that can help distinguish it from a genetic epilepsy syndrome.

Seizure Severity and Treatment Response in Newborn Infants with Seizures Attributed to Intracranial Hemorrhage.

OBJECTIVE: We sought to characterize intracranial hemorrhage (ICH) as a seizure etiology in infants born term and preterm. For infants born term, we sought to compare seizure severity and treatment response for multisite vs single-site ICH and hypoxic-ischemic encephalopathy (HIE) with vs without ICH. STUDY DESIGN: We studied 112 newborn infants with seizures attributed to ICH and 201 infants born at term with seizures attributed to HIE, using a cohort of consecutive infants with clinically diagnosed and/or electrographic seizures prospectively enrolled in the multicenter Neonatal Seizure Registry. We compared seizure severity and treatment response among infants with complicated ICH, defined as multisite vs single-site ICH and HIE with vs without ICH. RESULTS: ICH was a more common seizure etiology in infants born preterm vs term (27% vs 10%, P < .001). Most infants had subclinical seizures (74%) and an incomplete response to initial antiseizure medication (ASM) (68%). In infants born term, multisite ICH was associated with more subclinical seizures than single-site ICH (93% vs 66%, P = .05) and an incomplete response to the initial ASM (100% vs 66%, P = .02). Status epilepticus was more common in HIE with ICH vs HIE alone (38% vs 17%, P = .05). CONCLUSIONS: Seizure severity was greater and treatment response was lower among infants born term with complicated ICH. These data support the use of continuous video electroencephalogram monitoring to accurately detect seizures and a multistep treatment plan that considers early use of multiple ASMs, particularly with parenchymal and high-grade intraventricular hemorrhage and complicated ICH.

Predictors of Neurodevelopmental Impairment After Neonatal Bacterial Meningitis.

BACKGROUND: Neonatal bacterial meningitis has high rates of morbidity and mortality. Early clinical signs and neuroimaging suggest adverse outcomes, but little is known about their combined predictive properties. We evaluated the combination of findings most associated with death and neurodevelopmental impairment. METHODS: Single-center retrospective cohort study of term and late preterm neonates with bacterial meningitis. Predictors of death and neurodevelopmental impairment were identified on univariate analysis and incorporated into Lasso models to identify variables best predicting adverse outcomes. RESULTS: Of 103 neonates, 6 died acutely; 30% of survivors had neurodevelopmental impairment. Clinical variables (seizures, pressor support) predicted death and neurodevelopmental impairment better than the neuroimaging or combined findings (area under the curve 0.88 vs 0.79 and 0.83, respectively). Among survivors, neuroimaging findings (cerebrovascular lesions, ventriculomegaly) predicted neurodevelopmental impairment better than clinical or combined findings (area under the curve 0.82 vs 0.80 and 0.77, respectively). CONCLUSIONS: Seizures are important predictors of adverse outcomes in neonatal bacterial meningitis. Among survivors, neuroimaging findings help predict neurodevelopmental impairment.

MRI Score Ability to Detect Abnormalities in Mild Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Magnetic resonance imaging (MRI) scores have been well validated in moderate/severe hypoxic-ischemic encephalopathy (HIE). Infants with mild HIE can have different patterns of injury, yet different scores have not been compared in this group of infants. Our objective was to compare the ability of three = MRI scores to detect abnormalities in infants with mild HIE, and infants with moderate/severe HIE were included for comparison. METHODS: This is a single-center prospective cohort study of infants ≥36 weeks' gestation with HIE born at a level III neonatal intensive care unit from 2017 to 2019. All infants with HIE underwent an MRI, but only infants with moderate/severe HIE underwent therapeutic hypothermia. At least two experienced MRI readers who were unaware of all clinical variables independently assigned three scores (Barkovich, NICHD NRN, and Weeke). RESULTS: A total of 42 newborns with varying HIE severity underwent MRI on day five of life. In the overall cohort, abnormalities were reported in three (7%) infants using the Barkovich, in 10 (24%) using the NICHD NRN, and in 24 (57%) using the Weeke score. Agreement was excellent for each score: Barkovich score (k = 1.0), NICHD NRN (k = 0.92), and Weeke score (k = 0.9). CONCLUSIONS: Subtle injury due to mild HIE was detected with the highest frequency using the Weeke score, while inter-rater reliability was excellent for all three scores. These findings suggest that infants with mild HIE and subtle MRI abnormalities may benefit from detailed scoring systems, which is important for studies investigating the benefit of hypothermia in mild HIE.

Parent mental health and neurodevelopmental outcomes of children hospitalized in the neonatal intensive care unit.

High-risk infants hospitalized in the Neonatal Intensive Care Unit (NICU) often receive life-saving interventions during a critical period of development, when their brain is highly sensitive to both positive and negative environmental factors. It is no surprise that this time is particularly challenging for families. In fact, parents of hospitalized newborns are likely to experience clinically-significant symptoms of stress, anxiety, and depression. These symptoms have the potential to impact the nature and quality of the early parent-infant relationship and can lead to long-term problematic consequences for the infant and the family. As such, perinatal parent mental health represents a key factor that impacts outcomes of high-risk children. We discuss future practices to optimize the wellbeing of NICU infants and their families in the long-term, including increasing awareness and screening for parent mental health in the NICU, as well as building systems for support and early intervention.