About

Shavonne L Massey, MD, MSCE, is an Assistant Professor of Neurology at the Children's Hospital of Philadelphia. She holds clinical roles as an Attending Physician at multiple hospitals including the Children's Hospital of Philadelphia, Pennsylvania Hospital, Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Lancaster General Hospital, and Virtua Hospital. She is also a Clinical Associate at the Children's Hospital of Philadelphia and the Director of Neonatal Neurophysiology at the Children's Hospital of Philadelphia. Her clinical expertise encompasses EEG, epilepsy, neonatal brain injury, neonatal seizures, neurocritical care, and neurogenetics. Her research focuses on the diagnosis and management of seizures in high-risk neonatal populations, EEG biomarker development, and neurodevelopmental outcomes following neonatal seizures.

Research topics

• Internal medicine
• Medicine
• Pediatrics
• Psychiatry
• Intensive care medicine
• Emergency medicine

Selected publications

• Genetic testing for familial epilepsies: Diagnostic yield and genetic findings

  Epilepsia · 2026-03-08

  articleOpen access

  OBJECTIVE: Genetic testing has become a routine part of clinical epilepsy care. Family history is an indication for genetic testing, but the diagnostic yield, predictors of a genetic diagnosis, and association with familial patterns are not well understood. METHODS: This was a retrospective cohort study of genetic testing performed at pediatric and adult epilepsy genetics clinics. Eligible patients (probands) had epilepsy and one or more first-degree relatives or two or more other relatives with epilepsy. Genetic testing strategies were patient specific, reflecting real-world clinical practice. Familial patterns were classified based on affected relatives of the proband. Diagnostic variants were tested in the proband's parents when possible. RESULTS: (1) = 9.6, p = .002) and earlier age at seizure onset (Mann-Whitney U test, p < .001). The likelihood of a genetic diagnosis was not associated with epilepsy type, drug resistance, brain magnetic resonance imaging (MRI) findings, number of affected first-degree relatives, total number of affected relatives, or having an affected parent with epilepsy. Among those with genetic diagnoses, variant segregation matched the familial pattern of affected individuals in 79%. The other 21% of families had unexpected segregation, including de novo variants in patients with affected ancestors and inherited variants in patients with no known affected ancestors. SIGNIFICANCE: Familial epilepsy has a substantial rate of genetic diagnosis and is an appropriate indication for genetic testing. Pedigree-related factors did not influence the likelihood of genetic diagnosis, suggesting that all families can be considered for genetic testing, independent of inheritance patterns and number of affected relatives. Familial patterns can help interpret genetic test results, while also revealing the complexities of incomplete penetrance and independent epilepsy etiologies in families.

  PublisherDOI

• Profiles and Predictors of Neurodevelopmental Outcome at 5–6 Years in Children With a History of Acute Provoked Neonatal Seizures

  Annals of Neurology · 2026-01-03 · 1 citations

  articleOpen access

  OBJECTIVE: The objective of this study was to characterize the neurodevelopment and risk factors for impairment at age 5 to 6 years after acute provoked neonatal seizures. METHODS: Multicenter study of neonates with acute provoked seizures. Wechsler Preschool and Primary Scale of Intelligence IV (WPPSI-IV), Vineland-3 Adaptive Behavior Scales, Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Social Responsiveness Scale, cerebral palsy (CP), and epilepsy were assessed at age 5 to 6 years. Latent class analysis defined outcome profiles. Least absolute shrinkage and selection operator (LASSO) was used to determine outcome predictors. RESULTS: We characterized 3 latent classes among 164 children: (1) Typical Development (63%); (2) Behavioral Dysregulation (13%; low likelihood of physical impairment or severely impaired cognition, high likelihood of attention deficit hyperactivity disorder [ADHD]); and (3) Multi-Domain Impairment (24%; high likelihood of epilepsy and impairment across all domains). Among 144 children with standardized testing, mean WPPSI-IV was 91 ± 25 and Vineland-3 Adaptive Behavior Composite 90 ± 20. Twenty-nine percent had ADHD or elevated attention/hyperactivity scores; 19% had autism or elevated Social Responsiveness scores; 20% had epilepsy, and 19% had CP. Risk factors for Multi-Domain Impairment were abnormal neonatal neurologic examination (odds ratio [OR] = 3.94, 95% confidence interval [CI] = 1.74-8.95), impaired functional development at age 24 months (OR = 3.82, 95% CI = 1.25-11.66), and CP (OR = 3.71, 95% CI = 1.74-7.90). No neonatal or infant characteristics were significantly associated with Behavioral Dysregulation. INTERPRETATION: Nearly two-thirds of 5 to 6-year-old children with provoked neonatal seizures had typical development. Yet, executive and behavioral dysregulation were prevalent, even with preserved cognitive and physical function. These findings can inform outcome discussions and interventions to promote neurodevelopment. ANN NEUROL 2026;99:777-791.

  PublisherOA PDFDOI

• Long‐term safety of early discontinuation of antiseizure medication after resolution of acute provoked neonatal seizures

  Epilepsia · 2026-03-13

  articleOpen access

  OBJECTIVE: To assess long-term safety of antiseizure medication (ASM) discontinuation after resolution of acute provoked neonatal seizures and prior to hospital discharge. METHODS: Prospective, observational, comparative effectiveness cohort study of neonates with acute provoked seizures born from July 2015 to March 2018, and followed until September 2024, at nine U.S. Neonatal Seizure Registry centers with Level IV neonatal intensive care units and Level IV pediatric epilepsy programs. Duration of ASM treatment was quantified as (1) discontinuation before discharge from the neonatal seizure admission or (2) maintenance at the time of hospital discharge. Outcomes were adjusted for propensity to receive ASM at discharge. Propensity for ASM maintenance was defined among enrolled participants by a logistic regression model including seizure etiology, gestational age, therapeutic hypothermia, worst electroencephalography (EEG) background, days of EEG seizures, and discharge neurological exam (all p ≤ .1 in a joint model, except etiology, which was included for face validity). The primary outcome was non-inferiority of cognition (Wechsler Preschool and Primary Scale of Intelligence assessed at age 5-6 years). Secondary outcomes were non-inferiority of functional development (Vineland Adaptive Behavior Scale, 3rd Edition, assessed at 3-8 years) and post-neonatal epilepsy (assessed at 1-8 years). RESULTS: Among 284 children with at least one follow-up, outcomes were similar in the discontinued vs maintained ASM groups for full-scale IQ at age 5 years (adjusted difference +10 points), functional development at ages 3-8 years (adjusted difference 0 points), and post-neonatal epilepsy at ages 1-8 years (adjusted hazard ratio .93, 95% confidence interval [CI] .48-1.80). SIGNIFICANCE: Prolonged administration of ASM for several months after resolution of acute provoked neonatal seizures may expose infants to unnecessary medications. These results provide additional evidence for safety of discontinuing ASM for most neonates soon after the resolution of acute provoked seizures-a practice that is recommended in the International League Against Epilepsy (ILAE) guideline for neonatal seizure management.

  PublisherDOI

• Mechanistically informed circulating biomarkers are associated with acquired epilepsy after neonatal brain injury

  Journal of Neuroinflammation · 2026-05-09

  articleOpen access

  BACKGROUND: Acute provoked neonatal seizures are a major risk factor for acquired epilepsy, yet clinicians lack reliable tools to identify neonates at highest risk. Preclinical data implicate innate immune activation and neuronal injury as key drivers of epileptogenesis, suggesting blood-based biomarkers could provide mechanistic insight and prognostic utility. We sought to identify biomarkers of epileptogenesis in neonates with acute provoked seizures after brain injury using multicenter cohorts. METHODS: We conducted a prospective, multi-cohort analysis across two independent studies. NSR-RISE enrolled neonates with EEG-confirmed acute provoked seizures of diverse etiologies. The HEAL trial enrolled neonates with hypoxic-ischemic encephalopathy; analyses were limited to those with seizures. Plasma proteins were quantified 48-96 h after seizure onset. Associations with acquired epilepsy by 24-months were evaluated using log-link models with robust standard errors and false-discovery rate correction (FDR < 0.05). Significant proteins were added to models including established clinical predictors (≥ 3 days of EEG seizures and abnormal neurological examination at discharge). Exploratory pathway enrichment used KEGG databases. NSR-RISE participants also underwent plasma microRNA (miRNA) sequencing with integrative pathway analyses. RESULTS: Among 35 neonates in NSR-RISE, 7 (20%) developed epilepsy; among 40 neonates in HEAL, 6 (15%) developed epilepsy. Across both cohorts, neonates with epilepsy had higher concentrations of the pro-inflammatory cytokine IL-1β and the neuronal injury marker UCHL1 compared to those without epilepsy. Growth hormone (GH), measured only in NSR-RISE, was decreased in neonates with epilepsy. Incorporation of biomarkers improved prognostic accuracy for epilepsy beyond clinical features alone (Area under the precision-recall curve (AUPRC) 0.30 (95%CI, 0.28-0.32) versus 0.91 (95%CI, 0.89-0.92); p < 0.001). Pathway enrichment analyses implicated innate immune signaling, including TLR/IL1/NF-κB-related and MAPK-associated IL-17 signaling. miRNA profiling identified 11 species differentially expressed between neonates with and without epilepsy, including brain-enriched miRNAs. Network analysis identified a co-expression module enriched for let-7f-5p and miR-146a-5p targeting TLR/IL1/NF-κB, MAPK, and JAK/STAT pathways. CONCLUSIONS: Across two cohorts, mechanistically informed biomarkers were associated with acquired epilepsy after neonatal seizures. IL-1β, UCHL1, and GH reflect inflammation, neuronal injury, and impaired trophic signaling, while circulating miRNAs provide complementary mechanistic insight. Findings support a translational biomarker panel and highlight inflammation as a biologically plausible therapeutic target.

  PublisherDOI

• Sequence variants in HECTD1 result in a variable neurodevelopmental disorder

  The American Journal of Human Genetics · 2025-01-28 · 4 citations

  articleOpen access

  Dysregulation of genes encoding the homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases has been linked to cancer and structural birth defects. One member of this family, the HECT-domain-containing protein 1 (HECTD1), mediates developmental pathways, including cell signaling, gene expression, and embryogenesis. Through GeneMatcher, we identified 14 unrelated individuals with 15 different variants in HECTD1 (10 missense, 3 frameshift, 1 nonsense, and 1 splicing variant) with neurodevelopmental disorders (NDDs), including autism, attention-deficit/hyperactivity disorder, and epilepsy. Of these 15 HECTD1 variants, 10 occurred de novo, 3 had unknown inheritance, and 2 were compound heterozygous. While all individuals in this cohort displayed NDDs, no genotype-phenotype correlation was apparent. Conditional knockout of Hectd1 in the neural lineage in mice resulted in microcephaly, severe hippocampal malformations, and complete agenesis of the corpus callosum, supporting a role for Hectd1 in embryonic brain development. Functional studies of select variants in C. elegans revealed dominant effects, including either change-of-function or loss-of-function/haploinsufficient mechanisms, which may explain phenotypic heterogeneity. Significant enrichment of de novo variants in HECTD1 was also shown in an independent cohort of 53,305 published trios with NDDs or congenital heart disease. Thus, our clinical and functional data support a critical requirement of HECTD1 for human brain development.

  PublisherDOI

• Retrospective, Multicenter Study of Lacosamide to Treat Neonatal Seizures

  Annals of the Child Neurology Society · 2025-12-19

  articleOpen access

  ABSTRACT Objective Most antiseizure medications (ASMs) are prescribed off label for neonates. Lacosamide's efficacy in infants and availability in intravenous formulation suggest potential utility for neonates. We evaluated the safety and efficacy of lacosamide for neonatal seizures. Methods This 10‐center, retrospective study of neonates with seizures and lacosamide treatment initiated by ≤ 48 weeks postmenstrual age collected clinical data from medical records and electroencephalogram recordings. Lacosamide efficacy was determined by changes in seizure burden with lacosamide treatment and seizure cessation by hospital discharge. Potential adverse events were reviewed. Results Among 62 eligible neonates, 33 had acute provoked seizures while 29 had neonatal‐onset epilepsy; there was no difference in seizure type or baseline seizure severity between groups. There were high rates of pretreatment status epilepticus (48%) and treatment‐resistant seizures, with 93% receiving ≥ 3 ASMs before lacosamide. Most received intravenous lacosamide, with a median loading dose of 5.0 mg/kg and median daily dose of 7.3 mg/kg. Seizure cessation occurred in 37% of neonates; 21% had no additional ASM administered after lacosamide. Seizure burden, measured in seizure minutes per hour, was lower at both 4 h and 7 days following lacosamide administration. In addition, there was a median reduction in seizure frequency of 30 seizures per day at 7 and 30 days posttreatment ( p &lt; .05). Lacosamide was continued at discharge in most neonates (72%). Seventy adverse events were reported in 35 (56%) neonates. Four transient events with possible or unknown relationship to lacosamide were likely multifactorial in origin; none were cardiac arrhythmias. Summary Despite high rates of treatment‐resistant seizures in this neonatal cohort, 37% experienced seizure cessation and most remained on lacosamide at hospital discharge. Most adverse events were not attributed to lacosamide. These results favor use of lacosamide and provide a rationale for future prospective studies.

  PublisherOA PDFDOI

• Postneonatal epilepsy after acute provoked neonatal seizures: Incidence, predictors, and clinical burden in a multicenter cohort followed through early childhood

  Epilepsia · 2025-08-06 · 4 citations

  articleOpen access

  OBJECTIVE: Epilepsy is a known potential outcome following acute provoked neonatal seizures, but its onset, treatment patterns, and health care utilization through childhood remain poorly characterized. This study aimed to define the incidence and timing of postneonatal epilepsy, identify perinatal predictors, and describe the clinical burden of epilepsy among survivors of acute provoked neonatal seizures through early childhood. METHODS: This prospective, multicenter cohort study followed neonates with acute provoked seizures from the Neonatal Seizure Registry (NSR-II) in an extended follow-up through early childhood (Developmental Functional Evaluation). Neonatal clinical and neuroimaging data were collected, and epilepsy outcomes (including semiology, treatments, and health care use) were assessed annually through at least 5 years via structured interviews and medical record review. Kaplan-Meier and Cox proportional hazards models evaluated epilepsy risk, with data censored at loss to follow-up. RESULTS: Among 282 neonates evaluated for epilepsy in NSR-II, 183 (65%) continued into the extended follow-up study. Across the entire follow-up period through early childhood, 50 (18%) developed epilepsy, with a cumulative incidence of 21.6% (95% confidence interval [CI] = 16.7%-27.7%). Earlier epilepsy onset was associated with ≥3 days of neonatal seizures (hazard ratio [HR] = 2.8, 95% CI = 1.5-5.2), abnormal discharge neurological exam (HR = 2.4, 95% CI = 1.3-4.4), and deep gray/brainstem injury (HR = 2.4, 95% CI = 1.2-4.7). Prematurity (<37 weeks) was associated with later epilepsy onset (HR = 3.7, 95% CI = 2.0-6.8). Half (50%) of children with epilepsy developed intractable epilepsy, and 40% required intensive care unit admission. Despite this, only one child received vagus nerve stimulation, and none underwent other epilepsy surgeries. SIGNIFICANCE: These findings highlight the early and persistent epilepsy risk after neonatal seizures. Preterm infants face increased risk later in childhood compared to infants born at term. Risk factor stratification may improve early surveillance, guide clinical decisions, and support family counseling. The underutilization of epilepsy surgery in this cohort suggests multifactorial barriers that warrant further investigation.

  PublisherOA PDFDOI

• Parent and Family Well-Being and Associated Risk Factors as Children with Neonatal Seizures Reach Preschool and School-Age: A Longitudinal Cohort Study

  The Journal of Pediatrics Clinical Practice · 2025-05-16 · 1 citations

  articleOpen access

  To assess parent/family well-being when children with neonatal seizures reach 3-8 years of age and examine factors associated with parent/family well-being. One parent per surviving infant in the Neonatal Seizure Registry (NSR) -II was invited to complete validated surveys annually when children were between 3-8 years of age. Three outcomes were examined: 1) parent well-being (anxiety, depression, and quality of life); 2) parent post-traumatic stress symptoms; and 3) impact on the family. We used mixed model regression with random intercepts and guided backward elimination and included potential predictors that had bivariate associations p<0.10 in the multivariable analyses. Among 169 parents, 8-35% experienced symptoms of anxiety, depression, or post-traumatic stress. When children were 8 years of age, about 1 in 3 parents had moderate to severe anxiety symptoms, approximately double the general population, 1 in 5 had PTSD symptoms and depression symptom frequency was similar to the general population In the final models, only child social communication impairment was associated with poorer parental well-being or post-traumatic stress symptoms. Several child factors, including age at discharge from the neonatal admission, functional impairment at 24 months, social communication impairment, and receiving special services, were associated with greater impact on the family. Child social and functional health challenges following neonatal seizures were associated with poorer parent and family well-being across the preschool and early school years. Longitudinal screening of child social functioning, parent well-being, and family function is indicated for early detection and referral to treatment services.

  PublisherDOI

• White Matter Microstructural Abnormalities in Neonatal Onset Genetic Epilepsy

  Annals of Clinical and Translational Neurology · 2025-01-01

  preprintOpen access

  OBJECTIVE: Recent evidence indicates that epilepsy is associated with abnormal white matter. If seizures alter white matter, then the impact upon network function, epileptogenesis, and cognition could be pronounced in neonates undergoing rapid developmental myelination. Neonates with epilepsy due to nonstructural genetic causes provide a unique opportunity to determine whether neonates experiencing seizures have abnormal white matter structure. METHODS: This was a retrospective case-control study of term neonates treated in a level IV NICU between 2013 and 2020. Cases had confirmed or suspected genetic epilepsy, normal MRI, and no conditions known to independently impact white matter. Healthy controls had normal MRI and no relevant clinical diagnoses. White matter was assessed via fractional anisotropy (FA) and mean diffusivity (MD) from Diffusion Tensor Imaging (DTI) using Tract Based Spatial Statistics (TBSS). RESULTS: Fifty-eight neonates (19 cases, 39 controls) were included. There was significantly increased FA and decreased MD in the superior corona radiata of neonates with genetic epilepsy compared to healthy controls, controlling for sex and postmenstrual age at time of MRI. Additional association tracts (anterior and posterior corona radiata, tapetum, external capsule, superior and inferior fronto-occipital fasciculus) approached significance (p < 0.2). There was no significant correlation between mean FA or MD and EEG seizure burden or developmental outcome. INTERPRETATION: White matter microstructure is abnormal, with higher FA and lower MD, in major association tracts of neonates with genetic epilepsy compared to healthy controls. These results indicate that white matter is impacted early in neonatal epilepsies, emphasizing the global impact of early-onset seizures.

  PublisherDOI

• Diagnostic Yield of Genetic Testing in Adults with Epilepsy (P7-1.010)

  Neurology · 2024-04-09

  article

  To determine the yield of genetic testing in adults with epilepsy across various testing types (exome sequence, gene panel, microarray) and across patient characteristics (type of epilepsy, intellectual disability, drug resistance, and family history of epilepsy).

  PublisherDOI

Frequent coauthors

• Nicholas S. Abend

  Children's Hospital of Philadelphia

  607 shared

• Catherine J. Chu

  433 shared

• Janet S. Soul

  415 shared

• Courtney J. Wusthoff

  Stanford University

  398 shared

• Maria Roberta Cilio

  Cliniques Universitaires Saint-Luc

  364 shared

• Cameron Thomas

  328 shared

• Taeun Chang

  Children's National

  306 shared

• Sonia L. Bonifacio

  294 shared

Education

• B.A., Psychology

  Princeton University

  2005

• M.D.

  University of Maryland School of Medicine

  2009

• M.S., Epidemiology

  University of Pennsylvania School of Medicine

  2018