Evaluating the Role of Inflammation in Neonatal Epileptogenesis

Active, not recruiting

Brief Summary: The purpose of this study evaluate the relationship between inflammation and epilepsy in neonates with seizures after birth.

Detailed Description: Seizures are a common symptom of neurologic dysfunction in the neonatal period, affecting more than 16,000 newborns in the United States per year. Over 25% of neonates with acute symptomatic seizures develop post- neonatal epilepsy (PNE), which is often resistant to medical therapies. There is a critical need to identify those patients most at risk for PNE and understand the mechanisms by which early seizures increase the propensity for recurrent seizures, in hopes of identifying novel therapeutic targets in this population. There is increasing evidence for the role of neuro-inflammation in the development of epilepsy. Levels of cytokines and micro-RNA (miRNA) may serve as markers of disease severity and have been implicated in epileptogenesis in animal models. The purpose of this study is to evaluate plasma cytokine and miRNA levels after neonatal-onset acute symptomatic seizures and determine their association with acute seizure severity and PNE.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Neonates at risk for adverse outcome independent of seizures and underlying brain injury
Neonates with mild, temporary causes for seizures
Newborns with neonatal-onset epilepsy syndromes
Neonates who do not survive the initial hospital admission
Neonates will not be excluded based on race, ethnicity, gender or gestational age

For participants in the control group:

Inclusion Criteria:

Neonates that are born > 37 weeks and <44 weeks postmenstrual age at enrollment
Consultation by the pediatric neurology inpatient service due neonatal paroxysmal events, with normal neurologic examination and ultimate diagnosis of non-epileptic spells on continuous video-EEG (ordered for clinical purposes, not for research) OR consultation for hypoxic ischemic encephalopathy in neonates undergoing therapeutic hypothermia, with early exit from therapy owing to normal neurologic examination, normal continuous video-EEG and uncertain diagnosis of encephalopathy.
Neonates requiring neurologic consultation for mild hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia, with normal examination, cEEG, and neuroimaging upon rewarming.

Arm && Interventions

Group	Intervention	Description
Acute symptomatic seizures	Blood draw	This is a cohort of 72 participants who will be enrolled into this study from the neonatal intensive care unit (NICU) after being diagnosed with seizures. They will be asked to contribute a blood specimen obtained ideally 48-96 hours (though blood collection allowed 24-120 hours) after seizures are diagnosed, to participate in an optional blood draw at 2-4 months of age, and to complete surveys at 12 \& 24 months of age.
Acute symptomatic seizures	Survey	This is a cohort of 72 participants who will be enrolled into this study from the neonatal intensive care unit (NICU) after being diagnosed with seizures. They will be asked to contribute a blood specimen obtained ideally 48-96 hours (though blood collection allowed 24-120 hours) after seizures are diagnosed, to participate in an optional blood draw at 2-4 months of age, and to complete surveys at 12 \& 24 months of age.
Control	Blood draw	This is a cohort of 15 participants who will be enrolled into this study from the neonatal intensive care unit (NICU) after having an EEG for possible seizures, but found to have a normal EEG. They will be asked to contribute a blood specimen obtained ideally 48-96 hours (though blood collection allowed 24-120 hours) after birth.

Primary Outcome Measures

Name	Time	Method
Seizure burden	At study entry	Investigators will evaluate the seizure burden from the initial diagnostic electroencephalogram (EEG) after birth by determining the average number of seizures per hour.
Percentage of participants diagnosed with epilepsy	24 months of age	The investigators will determine the proportion of participants who develop clinical and or electrographic seizures.

Secondary Outcome Measures

Name	Time	Method
Epilepsy Severity	24 months of age	The investigators will administer an investigator-developed questionnaire designed to define the frequency of seizures (monthly, weekly, daily, or greater than daily).
Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS)	Assessment takes up to 15 minutes and will be conducted at 24 months of age	The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) will be assessed at 24 months of age. The score ranges from 50 to 200 with higher scores associated with normal development.
Percentage of participants diagnosed with epilepsy	12 months of age	The investigators will determine the proportion of participants who develop clinical and or electrographic seizures.

Locations (4): University of California, San Francisco
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San Francisco, California, United States
UCSF Benioff Children's Hospital Oakland
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Oakland, California, United States
University of Michigan, Mott Children's Hospital
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Ann Arbor, Michigan, United States
Boston Children's Hospital
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Boston, Massachusetts, United States