Bio

Academic Appointments


Administrative Appointments


  • Neurology Director, LPCH Neuro NICU, Lucile Packard Children's Hospital (2013 - Present)

Professional Education


  • Board Certification: Pediatrics, American Board of Pediatrics (2009)
  • Medical Education:University of California San Francisco (2004) CA
  • Fellowship:Children's Hospital of Philadelphia- Child Neurology (2010) PA
  • Board Certification: Neurology - Child Neurology, American Board of Psychiatry and Neurology (2009)
  • Residency:Children's Hospital of Oakland (2009) CA
  • Internship:Children's Hospital at Oakland (2006) CA

Research & Scholarship

Current Research and Scholarly Interests


My projects focus on clinical research in newborns with, or at risk, for brain injury. I use EEG in at-risk neonates to better understand the underlying pathophysiology of risk factors that may lead to worse outcomes. I am particularly interested in neonatal seizures and how they may exacerbate perinatal brain injury with a goal to identify treatments that might protect the vulnerable brain. I am also interested in EEG in other pediatric populations, as well as medical ethics and global health.

Teaching

2014-15 Courses


Publications

Journal Articles


  • How to use: amplitude-integrated EEG (aEEG) ARCHIVES OF DISEASE IN CHILDHOOD-EDUCATION AND PRACTICE EDITION Shah, N. A., Wusthoff, C. J. 2015; 100 (2): 75-81

    Abstract

    Amplitude-integrated electroencephalography (aEEG) is a method for continuous monitoring of brain activity that is increasingly used in the neonatal intensive care unit. In its simplest form, aEEG is a processed single-channel electroencephalogram that is filtered and time-compressed. Current evidence demonstrates that aEEG is useful to monitor cerebral background activity, diagnose and treat seizures and predict neurodevelopmental outcomes for preterm and term infants. This review aims to explain the fundamentals behind aEEG and its clinical applications.

    View details for DOI 10.1136/archdischild-2013-305676

    View details for Web of Science ID 000351216400004

    View details for PubMedID 25035312

  • Development and validation of a seizure prediction model in critically ill children SEIZURE-EUROPEAN JOURNAL OF EPILEPSY Yang, A., Arndt, D. H., Berg, R. A., Carpenter, J. L., Chapman, K. E., Dlugos, D. J., Gallentine, W. B., Giza, C. C., Goldstein, J. L., Hahn, C. D., Lerner, J. T., Loddenkemper, T., Matsumoto, J. H., Nash, K. B., Payne, E. T., Fernandez, I. S., Shults, J., Topjian, A. A., Williams, K., Wusthoff, C. J., Abend, N. S. 2015; 25: 104-111

    Abstract

    Electrographic seizures are common in encephalopathic critically ill children, but identification requires continuous EEG monitoring (CEEG). Development of a seizure prediction model would enable more efficient use of limited CEEG resources. We aimed to develop and validate a seizure prediction model for use among encephalopathic critically ill children.We developed a seizure prediction model using a retrospectively acquired multi-center database of children with acute encephalopathy without an epilepsy diagnosis, who underwent clinically indicated CEEG. We performed model validation using a separate prospectively acquired single center database. Predictor variables were chosen to be readily available to clinicians prior to the onset of CEEG and included: age, etiology category, clinical seizures prior to CEEG, initial EEG background category, and inter-ictal discharge category.The model has fair to good discrimination ability and overall performance. At the optimal cut-off point in the validation dataset, the model has a sensitivity of 59% and a specificity of 81%. Varied cut-off points could be chosen to optimize sensitivity or specificity depending on available CEEG resources.Despite inherent variability between centers, a model developed using multi-center CEEG data and few readily available variables could guide the use of limited CEEG resources when applied at a single center. Depending on CEEG resources, centers could choose lower cut-off points to maximize identification of all patients with seizures (but with more patients monitored) or higher cut-off points to reduce resource utilization by reducing monitoring of lower risk patients (but with failure to identify some patients with seizures).

    View details for DOI 10.1016/j.seizure.2014.09.013

    View details for Web of Science ID 000349881100019

  • Impact of bilirubin-induced neurologic dysfunction on neurodevelopmental outcomes. Seminars in fetal & neonatal medicine Wusthoff, C. J., Loe, I. M. 2015; 20 (1): 52-57

    Abstract

    Bilirubin-induced neurologic dysfunction (BIND) is the constellation of neurologic sequelae following milder degrees of neonatal hyperbilirubinemia than are associated with kernicterus. Clinically, BIND may manifest after the neonatal period as developmental delay, cognitive impairment, disordered executive function, and behavioral and psychiatric disorders. However, there is controversy regarding the relative contribution of neonatal hyperbilirubinemia versus other risk factors to the development of later neurodevelopmental disorders in children with BIND. In this review, we focus on the empiric data from the past 25 years regarding neurodevelopmental outcomes and BIND, including specific effects on developmental delay, cognition, speech and language development, executive function, and the neurobehavioral disorders, such as attention deficit/hyperactivity disorder and autism.

    View details for DOI 10.1016/j.siny.2014.12.003

    View details for PubMedID 25585889

  • Electrographic seizures are associated with brain injury in newborns undergoing therapeutic hypothermia ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION Shah, D. K., Wusthoff, C. J., Clarke, P., Wyatt, J. S., Ramaiah, S. M., Dias, R. J., Becher, J., Kapellou, O., Boardman, J. P. 2014; 99 (3): F219-F224

    Abstract

    Seizures are common among newborns with hypoxic-ischaemic encephalopathy (HIE) but the relationship between seizure burden and severity of brain injury among neonates receiving therapeutic hypothermia (TH) for HIE is unclear. We tested the hypothesis that seizure burden is associated with cerebral tissue injury independent of amplitude-integrated EEG (aEEG) background activity.Term neonates undergoing 72 h of TH at four centres were selected for study if they had continuous aEEG and MRI. The aEEG with corresponding 2-channel raw EEG (aEEG/EEG), was classified by severity of background and seizure burden; MR images were classified by the severity of tissue injury.Of 85 neonates, 52% had seizures on aEEG/EEG. Overall, 35% had high seizure burden, 49% had abnormal aEEG background in the first 24 h and 36% had severe injury on MRI. Seizures were most common on the first day, with significant recurrence during and after rewarming. Factors associated with severe injury on MRI were high seizure burden, poor aEEG background, 10 min Apgar and the need for more than one anticonvulsant. In multivariate logistic regression, high seizure burden was independently associated with greater injury on MRI (OR 5.00, 95% CI 1.47 to 17.05 p=0.01). Neither aEEG background, nor 10 min Apgar score were significant.Electrographic seizure burden is associated with severity of brain injury on MRI in newborns with HIE undergoing TH, independent of degree of abnormality on aEEG background. Seizures are common during cooling, particularly on day 1, with a significant rebound on day 4.

    View details for DOI 10.1136/archdischild-2013-305206

    View details for Web of Science ID 000334673600011

    View details for PubMedID 24443407

  • Risk factors for EEG seizures in neonates treated with hypothermia A multicenter cohort study NEUROLOGY Glass, H. C., Wusthoff, C. J., Shellhaas, R. A., Tsuchida, T. N., Bonifacio, S. L., Cordeiro, M., Sullivan, J., Abend, N. S., Chang, T. 2014; 82 (14): 1239-1244

    Abstract

    To assess the risk factors for electrographic seizures among neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE).Three-center observational cohort study of 90 term neonates treated with hypothermia, monitored with continuous video-EEG (cEEG) within the first day of life (median age at onset of recording 9.5 hours, interquartile range 6.3-14.5), and continued for >24 hours (total recording 93.3 hours, interquartile range 80.1-112.8 among survivors). A pediatric electroencephalographer at each site reviewed cEEGs for electrographic seizures and initial EEG background category.A total of 43 (48%) had electrographic seizures, including 9 (10%) with electrographic status epilepticus. Abnormal initial EEG background classification (excessively discontinuous, depressed and undifferentiated, burst suppression, or extremely low voltage), but not clinical variables (including pH <6.8, base excess ?-20, or 10-minute Apgar ?3), was strongly associated with seizures.Electrographic seizures are common among neonates with HIE undergoing hypothermia and are difficult to predict based on clinical features. These results justify the recommendation for cEEG monitoring in neonates treated with hypothermia.

    View details for DOI 10.1212/WNL.0000000000000282

    View details for Web of Science ID 000336497000014

    View details for PubMedID 24610326

  • Electrographic seizures and status epilepticus in critically ill children and neonates with encephalopathy LANCET NEUROLOGY Abend, N. S., Wusthoff, C. J., Goldberg, E. M., Dlugos, D. J. 2013; 12 (12): 1170-1179

    Abstract

    Electrographic seizures are seizures that are evident on EEG monitoring. They are common in critically ill children and neonates with acute encephalopathy. Most electrographic seizures have no associated clinical changes, and continuous EEG monitoring is necessary for identification. The effect of electrographic seizures on outcome is the focus of active investigation. Studies have shown that a high burden of electrographic seizures is associated with worsened clinical outcome after adjustment for cause and severity of brain injury, suggesting that a high burden of such seizures might independently contribute to secondary brain injury. Further research is needed to determine whether identification and management of electrographic seizures reduces secondary brain injury and improves outcome in critically ill children and neonates.

    View details for Web of Science ID 000327924100012

    View details for PubMedID 24229615

  • Amplitude-Integrated Electro-encephalography The Child Neurologist's Perspective JOURNAL OF CHILD NEUROLOGY Glass, H. C., Wusthoff, C. J., Shellhaas, R. A. 2013; 28 (10): 1342-1350

    Abstract

    Neurologists increasingly recognize that critically ill patients are at high risk for seizures, particularly nonconvulsive seizures, and that neuromonitoring is a useful tool for diagnosing seizures and assessing brain function in these patients. Amplitude-integrated electroencephalography (EEG) is a simplified bedside neurophysiology tool that has become widely used in neonates over the past decade. Despite widespread interest by both neurologists and neonatologists in continuous brain monitoring, amplitude-integrated EEG has been largely ignored by neurologists, forcing neonatologists to "go it alone" when interpreting data from this bedside tool. Although amplitude-integrated EEG cannot replace conventional EEG for background monitoring and detection of seizures, it remains a useful instrument that complements conventional EEG, is being widely adopted by neonatologists, and should be supported by neonatal neurologists.

    View details for DOI 10.1177/0883073813488663

    View details for Web of Science ID 000324399300025

    View details for PubMedID 23690296

  • Neurodevelopmental outcome in children with congenital heart disease SEMINARS IN FETAL & NEONATAL MEDICINE Martinez-Biarge, M., Jowett, V. C., Cowan, F. M., Wusthoff, C. J. 2013; 18 (5): 279-285

    Abstract

    Children with congenital heart disease (CHD) have multiple factors contributing toward their risk of later neurodevelopmental difficulties. With earlier diagnosis and improved survival rates, the management of CHD now includes the recognition of neurodevelopmental risks and optimisation of neurodevelopmental outcomes is emphasised. Neuroimaging studies have shown early differences in brain development for children with CHD, who then are vulnerable to additional brain injury in the perinatal period. For some children, complications and co-morbidities may further increase the risk of brain injury. Synthesis of multiple factors is necessary to estimate neurodevelopmental prognosis for an individual child. Long-term neurodevelopmental follow-up of children with CHD is warranted for early identification of and intervention for difficulties.

    View details for DOI 10.1016/j.siny.2013.04.006

    View details for Web of Science ID 000325905300007

    View details for PubMedID 23706956

  • How to use: the neonatal neurological examination ARCHIVES OF DISEASE IN CHILDHOOD-EDUCATION AND PRACTICE EDITION Wusthoff, C. J. 2013; 98 (4): 148-153

    Abstract

    The neurological exam can be a challenging part of a newborn's full evaluation. At the same time, the neonatal neurological exam is a useful tool in identifying babies needing closer evaluation for potential problems. The Dubowitz assessment is a standardised approach to the neonatal neurological exam designed for use by paediatricians in routine practice. Evidence has validated this technique and delineated its utility as a screening exam in various populations. This paper reviews clinical application of the Dubowitz assessment of the newborn.

    View details for DOI 10.1136/archdischild-2013-303640

    View details for Web of Science ID 000325865100010

    View details for PubMedID 23761325

  • Genetic testing in children with epilepsy. Continuum (Minneapolis, Minn.) Wusthoff, C. J., Olson, D. M. 2013; 19 (3 Epilepsy): 795-800

    Abstract

    Genetic testing is now available clinically for several epilepsies. Neurologists increasingly face decisions about diagnostic testing in affected patients and should carefully deliberate the ethical considerations associated with genetic testing. The merits of ordering a genetic test are largely based on the utility for guiding clinical care, providing a prognosis, estimating recurrence risk, and identifying comorbidities. At the same time, a decision to pursue any genetic testing also requires evaluation of associated ethical concerns. This case illustrates ethical challenges that arise when considering genetic testing for a pediatric patient with epilepsy.

    View details for DOI 10.1212/01.CON.0000431393.39099.89

    View details for PubMedID 23739111

  • Diagnosing Neonatal Seizures and Status Epilepticus JOURNAL OF CLINICAL NEUROPHYSIOLOGY Wusthoff, C. J. 2013; 30 (2): 115-121

    Abstract

    Continuous electroencephalographic (CEEG) monitoring is often applied in the Neonatal Intensive Care Unit to aid in the diagnosis and management of seizures. Neonatal seizures are particularly difficult to identify on the basis of clinical observation alone; diagnosis is greatly facilitated by CEEG monitoring. There is building evidence to suggest which neonates are at highest risk for seizures, and how CEEG can aid diagnosis. For the neurophysiologist, the unique features of neonatal seizures can distinguish them from nonictal patterns. These features include duration, location, morphology, and evolution. At the extreme, very frequent or prolonged neonatal seizures constitute status epilepticus. There is no consensus definition for neonatal status epilepticus, although the proposed criteria share some features. This article reviews available evidence to guide the application and interpretation of CEEG in the diagnosis of neonatal seizures and status epilepticus.

    View details for DOI 10.1097/WNP.0b013e3182872932

    View details for Web of Science ID 000316943400003

    View details for PubMedID 23545761

  • American Clinical Neurophysiology Society Standardized EEG Terminology and Categorization for the Description of Continuous EEG Monitoring in Neonates: Report of the American Clinical Neurophysiology Society Critical Care Monitoring Committee JOURNAL OF CLINICAL NEUROPHYSIOLOGY Tsuchida, T. N., Wusthoff, C. J., Shellhaas, R. A., Abend, N. S., Hahn, C. D., Sullivan, J. E., Nguyen, S., Weinstein, S., Scher, M. S., Riviello, J. J., Clancy, R. R. 2013; 30 (2): 161-173

    View details for DOI 10.1097/WNP.0b013e3182872b24

    View details for Web of Science ID 000316943400009

    View details for PubMedID 23545767

  • Hypoglycaemia and neonatal brain injury ARCHIVES OF DISEASE IN CHILDHOOD-EDUCATION AND PRACTICE EDITION Boardman, J. P., Wusthoff, C. J., Cowan, F. M. 2013; 98 (1): 2-6
  • White Matter and Cortical Injury in Hypoxic-Ischemic Encephalopathy: Antecedent Factors and 2-Year Outcome JOURNAL OF PEDIATRICS Martinez-Biarge, M., Bregant, T., Wusthoff, C. J., Chew, A. T., Diez-Sebastian, J., Rutherford, M. A., Cowan, F. M. 2012; 161 (5): 799-807

    Abstract

    To examine the spectrum of isolated white matter (WM)/cortical injury and its relation to outcomes in infants with hypoxic-ischemic encephalopathy (HIE) and normal appearing basal ganglia and thalami.From 1992-2007, 84 term infants with HIE and normal basal ganglia and thalami on neonatal magnetic resonance imaging were studied; WM/cortical lesions were classified by site and severity. Neurodevelopmental outcomes and head growth were documented at a median age of 2 years.The WM was normal or mildly abnormal in 33.5%, moderate in 40.5%, and severely abnormal in 26% of infants. Cortical involvement was not seen or was only mild in 75.5%, moderate in 13%, and severe in 12% of infants. WM and cortical injury severity were highly correlated (Spearman ? = 0.74; P < .001). Infants with severe WM injury had more severe neonatal courses and a higher incidence of hypoglycemia. No infant died. Five infants (6%) developed cerebral palsy but all could walk independently. Cognitive, visual, language, behavioral, and seizure problems were highly prevalent and correlated significantly with the severity of WM injury and poor postnatal head growth.Infants with HIE and selective WM/cortical injury have a low prevalence of cerebral palsy but have a wide range of other problems, which occur more often with severe WM/cortical lesions.

    View details for DOI 10.1016/j.jpeds.2012.04.054

    View details for Web of Science ID 000310370600009

    View details for PubMedID 22682614

  • Feeding and communication impairments in infants with central grey matter lesions following perinatal hypoxic-ischaemic injury EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY Martinez-Biarge, M., Diez-Sebastian, J., Wusthoff, C. J., Lawrence, S., Aloysius, A., Rutherford, M. A., Cowan, F. M. 2012; 16 (6): 688-696

    Abstract

    Basal ganglia and thalamic (BGT) injury is common after acute perinatal hypoxia-ischaemia. Cerebral palsy is the most obvious consequence of BGT injury affecting 70-75% of survivors and is predictable from neonatal magnetic resonance imaging (MRI). However there is no equivalent predictive data for other specific outcomes. Feeding and communication impairments are also common in children following hypoxic-ischaemic encephalopathy (HIE) and BGT injury.To describe, in infants with HIE and BGT injury, the prevalence of feeding and communication impairments; and to evaluate the accuracy of early MRI for predicting these outcomes.175 term infants with HIE and BGT injury were studied. Brain lesions were classified by site and severity from the MRI scans. Motor, feeding and communication impairments were documented at 2 years.Feeding and communication impairments occurred in 65% and 82% of 126 survivors respectively and related strongly to the severity of motor impairment. Forty-one children had a gastrostomy or long-term nasogastric tube. Injury severity in all brain regions was significantly associated with feeding and communication impairment on univariate analysis. On logistic regression analysis BGT (OR 10.9) and mesencephalic lesions (OR 3.7) were independently associated with feeding impairment; BGT (OR 10.5) and pontine lesions (OR 3.8) were associated with gastrostomy; the severity of BGT lesions (OR 20.1) was related to the severity of communication impairment.Feeding and communication impairment are very common in children with BGT and brainstem injury of neonatal origin and can be well predicted from early MRI scans.

    View details for DOI 10.1016/j.ejpn.2012.05.001

    View details for Web of Science ID 000310862800019

    View details for PubMedID 22658307

  • Neonatal Seizures and Status Epilepticus JOURNAL OF CLINICAL NEUROPHYSIOLOGY Abend, N. S., Wusthoff, C. J. 2012; 29 (5): 441-448

    Abstract

    Neonatal seizures are common, often require EEG monitoring for diagnosis and management, may be associated with worse neurodevelopmental outcome, and can often be treated with existing anticonvulsants. A neonatal electrographic seizure is defined as a sudden, repetitive, evolving, and stereotyped event of abnormal electrographic pattern with amplitude of at least 2 ?V and a minimum duration of 10 seconds. The diagnosis of neonatal seizures relies heavily on the neurophysiologist's interpretation of EEG. Consideration of specific criteria for the definition of a neonatal seizure, including seizure duration, location, morphology, evolution, semiology, and overall seizure burden, has utility for both the clinician and the researcher. The importance of EEG in the diagnosis and management of neonatal seizures, the electrographic characteristics of neonatal seizures, the impact of neonatal seizures on outcome, and tools to aid in the identification of neonatal seizures are reviewed.

    View details for DOI 10.1097/WNP.0b013e31826bd90d

    View details for Web of Science ID 000309547600012

    View details for PubMedID 23027101

  • Prediction of neurodevelopmental outcome after hypoxic-ischemic encephalopathy treated with hypothermia by diffusion tensor imaging analyzed using tract-based spatial statistics PEDIATRIC RESEARCH Tusor, N., Wusthoff, C., Smee, N., Merchant, N., Arichi, T., Allsop, J. M., Cowan, F. M., Azzopardi, D., Edwards, A. D., Counsell, S. J. 2012; 72 (1): 63-69

    Abstract

    Objective biomarkers are needed to assess neuroprotective therapies after perinatal hypoxic-ischemic encephalopathy (HIE). We tested the hypothesis that, in infants who underwent therapeutic hypothermia after perinatal HIE, neurodevelopmental performance was predicted by fractional anisotropy (FA) values in the white matter (WM) on early diffusion tensor imaging (DTI) as assessed by means of tract-based spatial statistics (TBSS).We studied 43 term infants with HIE. Developmental assessments were carried out at a median (range) age of 24 (12-28) mo.As compared with infants with favorable outcomes, those with unfavorable outcomes had significantly lower FA values (P < 0.05) in the centrum semiovale, corpus callosum (CC), anterior and posterior limbs of the internal capsule, external capsules, fornix, cingulum, cerebral peduncles, optic radiations, and inferior longitudinal fasciculus. In a second analysis in 32 assessable infants, the Griffiths Mental Development Scales (Revised) (GMDS-R) showed a significant linear correlation (P < 0.05) between FA values and developmental quotient (DQ) and all its component subscale scores.DTI analyzed by TBSS provides a qualified biomarker that can be used to assess the efficacy of additional neuroprotective therapies after HIE.

    View details for DOI 10.1038/pr.2012.40

    View details for Web of Science ID 000305440100010

    View details for PubMedID 22447318

  • Amplitude-integrated electroencephalography: a runaway horse? Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques Dysart, K. C., Kirpalani, H. M., Kirpalani, H. M., Wusthoff, C. J., Seshia, S. S. 2012; 39 (3): 267-268

    View details for PubMedID 22547504

  • Modified Pediatric ASPECTS Correlates with Infarct Volume in Childhood Arterial Ischemic Stroke. Frontiers in neurology Beslow, L. A., Vossough, A., Dahmoush, H. M., Kessler, S. K., Stainman, R., Favilla, C. G., Wusthoff, C. J., Zelonis, S., Licht, D. J., Ichord, R. N., Smith, S. E. 2012; 3: 122-?

    Abstract

    Background and Purpose: Larger infarct volume as a percent of supratentorial brain volume (SBV) predicts poor outcome and hemorrhagic transformation in childhood arterial ischemic stroke (AIS). In perinatal AIS, higher scores on a modified pediatric version of the Alberta Stroke Program Early CT Score using acute MRI (modASPECTS) predict later seizure occurrence. The objectives were to establish the relationship of modASPECTS to infarct volume in perinatal and childhood AIS and to establish the interrater reliability of the score. Methods: We performed a cross sectional study of 31 neonates and 40 children identified from a tertiary care center stroke registry with supratentorial AIS and acute MRI with diffusion weighted imaging (DWI) and T2 axial sequences. Infarct volume was expressed as a percent of SBV using computer-assisted manual segmentation tracings. ModASPECTS was performed on DWI by three independent raters. The modASPECTS were compared among raters and to infarct volume as a percent of SBV. Results: ModASPECTS correlated well with infarct volume. Spearman rank correlation coefficients (?) for the perinatal and childhood groups were 0.76, p?

    View details for PubMedID 23015799

  • The American Clinical Neurophysiology Society's Guideline on Continuous Electroencephalography Monitoring in Neonates JOURNAL OF CLINICAL NEUROPHYSIOLOGY Shellhaas, R. A., Chang, T., Tsuchida, T., Scher, M. S., Riviello, J. J., Abend, N. S., Sylvie Nguyen, S., Wusthoff, C. J., Clancy, R. R. 2011; 28 (6): 611-617

    View details for Web of Science ID 000298821700012

    View details for PubMedID 22146359

  • Risk of Later Seizure After Perinatal Arterial Ischemic Stroke: A Prospective Cohort Study PEDIATRICS Wusthoff, C. J., Kessler, S. K., Vossough, A., Ichord, R., Zelonis, S., Halperin, A., Gordon, D., Vargas, G., Licht, D. J., Smith, S. E. 2011; 127 (6): E1550-E1557

    Abstract

    Although acute seizures are common among neonates with arterial ischemic stroke (AIS), the incidence of subsequent seizures is unknown. The goals of this study were to determine the incidence of seizures following hospital discharge after perinatal acute AIS, and to assess lesion characteristics associated with later seizure occurrence.Neonates with confirmed acute AIS on MRI were identified through a prospective stroke registry. Clinic visits and telephone follow-up identified occurrence of seizures after hospital discharge. MRI scans were graded for size and characteristics of infarct, and associations with seizures after stroke were analyzed.At a mean (SD) follow-up of 31.3 (16.1) months, 11 of 46 (23.9%) patients with perinatal AIS had at least 1 seizure. Five patients had a single episode of seizure, and 6 developed epilepsy. The Kaplan-Meier probability of remaining seizure-free at 3 years was 73%. Stroke size on MRI was significantly associated with development of later seizures, with an incidence rate of later seizures 6.2 times higher among those with larger stroke size.Seizures occurred in <25% of patients during initial follow-up after perinatal AIS. Of those with seizures, nearly half had a single episode of seizure and not early epilepsy. Larger stroke size was associated with higher risk of seizure. These data suggest that prolonged treatment with anticonvulsant agents may not be indicated for seizure prophylaxis after perinatal AIS. These findings may help guide clinicians in counseling families and could form the basis for much-needed future research in this area.

    View details for DOI 10.1542/peds.2010-1577

    View details for Web of Science ID 000291146100024

    View details for PubMedID 21576305

  • Electrographic Seizures During Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy JOURNAL OF CHILD NEUROLOGY Wusthoff, C. J., Dlugos, D. J., Gutierrez-Colina, A., Wang, A., Cook, N., Donnelly, M., Clancy, R., Abend, N. S. 2011; 26 (6): 724-728

    Abstract

    Electrographic seizures are common in neonates with hypoxic-ischemic encephalopathy, but detailed data are not available regarding seizure incidence during therapeutic hypothermia. The objective of this prospective study was to determine the incidence and timing of electrographic seizures in term neonates undergoing whole-body therapeutic hypothermia for hypoxic-ischemic encephalopathy as detected by conventional full-array electroencephalography for 72 hours of therapeutic hypothermia and 24 hours of normothermia. Clinical and electroencephalography data were collected from 26 consecutive neonates. Electroencephalograms were reviewed by 2 pediatric neurophysiologists. Electrographic seizures occurred in 17 of 26 (65%) patients. Seizures were entirely nonconvulsive in 8 of 17 (47%), status epilepticus occurred in 4 of 17 (23%), and seizure onset was in the first 48 hours in 13 of 17 (76%) patients. Electrographic seizures were common, were often nonconvulsive, and had onset over a broad range of times in the first days of life.

    View details for DOI 10.1177/0883073810390036

    View details for Web of Science ID 000290961000009

    View details for PubMedID 21447810

  • The ketogenic diet in treatment of two adults with prolonged nonconvulsive status epilepticus EPILEPSIA Wusthoff, C. J., Kranick, S. M., Morley, J. F., Bergqvist, A. G. 2010; 51 (6): 1083-1085

    Abstract

    Prolonged status epilepticus (SE) can be refractory to conventional interventions, with high rates of subsequent morbidity and mortality. A high fat, low protein, low carbohydrate ketogenic diet (KD) has been used successfully to treat intractable epilepsy. However, its possible role in prolonged SE has not been well described. We report successful use of the KD in two adult patients with prolonged nonconvulsive SE (NCSE) refractory to multiple other interventions. Our observations suggest induction of ketosis may be a novel strategy to safely and effectively treat status in adults even after weeks to months of refractory seizures. Although there are few data regarding the use of the ketogenic diet in the treatment of adult epilepsy syndromes, it may be an option for the treatment of adults with refractory, prolonged SE.

    View details for DOI 10.1111/j.1528-1167.2009.02388.x

    View details for Web of Science ID 000278307900019

    View details for PubMedID 19845731

  • Interictal EEG spikes identify the region of electrographic seizure onset in some, but not all, pediatric epilepsy patients EPILEPSIA Marsh, E. D., Peltzer, B., Brown, M. W., Wusthoff, C., Storm, P. B., Litt, B., Porter, B. E. 2010; 51 (4): 592-601

    Abstract

    The role of sharps and spikes, interictal epileptiform discharges (IEDs), in guiding epilepsy surgery in children remains controversial, particularly with intracranial electroencephalography (IEEG). Although ictal recording is the mainstay of localizing epileptic networks for surgical resection, current practice dictates removing regions generating frequent IEDs if they are near the ictal onset zone. Indeed, past studies suggest an inconsistent relationship between IED and seizure-onset location, although these studies were based upon relatively short EEG epochs.We employ a previously validated, computerized spike detector to measure and localize IED activity over prolonged, representative segments of IEEG recorded from 19 children with intractable, mostly extratemporal lobe epilepsy. Approximately 8 h of IEEG, randomly selected 30-min segments of continuous interictal IEEG per patient, were analyzed over all intracranial electrode contacts.When spike frequency was averaged over the 16-time segments, electrodes with the highest mean spike frequency were found to be within the seizure-onset region in 11 of 19 patients. There was significant variability between individual 30-min segments in these patients, indicating that large statistical samples of interictal activity were required for improved localization. Low-voltage fast EEG at seizure onset was the only clinical factor predicting IED localization to the seizure-onset region.Our data suggest that automated IED detection over multiple representative samples of IEEG may be of utility in planning epilepsy surgery for children with intractable epilepsy. Further research is required to better determine which patients may benefit from this technique a priori.

    View details for DOI 10.1111/j.1528-1167.2009.02306.x

    View details for Web of Science ID 000276245600012

    View details for PubMedID 19780794

  • Limitations of single-channel EEG on the forehead for neonatal seizure detection JOURNAL OF PERINATOLOGY Wusthoff, C. J., Shellhaas, R. A., Clancy, R. R. 2009; 29 (3): 237-242

    Abstract

    In amplitude-integrated EEG, lead placement across the forehead is convenient, but this location has unknown effects on neonatal seizure (NS) detection sensitivity. This study describes the limits of NS detection by a single forehead EEG channel.Records were taken from a digital library of conventional EEGs (CEEGs) with NS, previously characterized at a bicentral channel, C(3) --> C(4). We analyzed electrographic characteristics in a single forehead channel, Fp(3) --> Fp(4).A total of 330 seizures from 125 CEEGs were included. With Fp(3) --> Fp(4), at least one NS was detected in 66% of records vs 90% using C(3) --> C(4) (P<0.0001). Of 330 seizures, 46% appeared in Fp(3) --> Fp(4) vs 73% in C(3) --> C(4) (P<0.0001). Seizures appeared briefer in Fp(3) --> Fp(4) than C(3) --> C(4) (P<0.006) and CEEG (P<0.0001).NSs are significantly more difficult to detect with a single forehead channel than bicentrally or on CEEG. In Fp(3) --> Fp(4), a third of records with seizures were missed and over half of seizures were undetected.

    View details for DOI 10.1038/jp.2008.195

    View details for Web of Science ID 000263893500011

    View details for PubMedID 19052554

  • Hemosiderin-laden macrophages in the cerebrospinal fluid of a neonate after traumatic lumbar puncture PEDIATRIC INFECTIOUS DISEASE JOURNAL Wusthoff, C. J., Abend, N. S., Tennekoon, G. 2008; 27 (1): 83-84

    Abstract

    Macrophages in cerebrospinal fluid are described as indicators of pathology. We present findings from the lumbar puncture of a child without neurologic disease. Cerebrospinal fluid obtained after an initial, traumatic lumbar puncture attempt included a high proportion of macrophages, some containing erythrocyte fragments and hemosiderin. This suggests that although macrophages may indicate pathology, they can also accumulate after traumatic lumbar puncture.

    View details for DOI 10.1097/INF.0b013e3181506463

    View details for Web of Science ID 000252076200022

    View details for PubMedID 18162950

  • Management of common neurologic symptoms in pediatric palliative care: Seizures, agitation, and spasticity PEDIATRIC CLINICS OF NORTH AMERICA Wusthoff, C. J., Shellhaas, R. A., Licht, D. J. 2007; 54 (5): 709-?

    Abstract

    Palliative care for children is complex and focuses on patients' comfort. Some of the most troublesome symptoms as patients approach the end of life are seizures, agitation, and spasticity. Many doctors caring for children at the end of life are uncomfortable or untrained in managing these symptoms in children. Our goal is to help physicians recognize and treat these neurologic symptoms optimally.

    View details for DOI 10.1016/j.pcl.2007.06.004

    View details for Web of Science ID 000252210800008

    View details for PubMedID 17933619

  • Differences in pediatric oncologists' estimates of curability and treatment recommendations for patients with advanced cancer: Response PEDIATRIC BLOOD & CANCER Wusthoff, C. J., Ablin, A. R., McMillan, A. 2005; 45 (3): 358-358

    View details for DOI 10.1002/pbc.20410

    View details for Web of Science ID 000230740000025

  • Differences in pediatric oncologists' estimates of curability and treatment recommendations for patients with advanced cancer PEDIATRIC BLOOD & CANCER Wusthoff, C. J., McMillan, A., Ablin, A. R. 2005; 44 (2): 174-181

    Abstract

    When goals of therapy for children with advanced cancer are called into question, physician recommendations regarding treatment goals have been shown to be important for families. However, there has been no demonstration of the degree of variation between pediatric oncologists' recommendations in such situations.We provided 48 pediatric oncologists with two identical case histories and identical prognostic data from the literature. Individual interviews were then performed to assess variation in (1) recommended treatment goal, (2) perceived chances for cure, and (3) degree to which further curative intervention would be considered desirable for each patient.There was a large variability in each of the areas examined. For both patients, there was wide divergence (2:1 and 2:3) in whether to recommend cure as the goal of treatment. There were also differences in physician estimates for likelihood of cure for each patient. Finally, even among those with identical estimates for likelihood of cure, there were differences in the treatment goals physicians would recommend and how strongly they would counsel for them.This study demonstrates that even with identical clinical data and prognostic evidence from the literature, pediatric oncologists vary widely in their recommendations regarding goals of treatment for children with advanced cancer.

    View details for DOI 10.1002/pbc.20153

    View details for Web of Science ID 000225904600012

    View details for PubMedID 15390284

  • The dilemma of confidentiality in Huntington disease JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Wusthoff, C. 2003; 290 (9): 1219-1220

    View details for Web of Science ID 000185090400022

    View details for PubMedID 12953009

  • Medical mistakes and disclosure: The role of the medical student JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Wusthoff, C. J. 2001; 286 (9): 1080-1081

    View details for Web of Science ID 000170802500025

    View details for PubMedID 11559297

  • Numerical subtraction in the pigeon: Evidence for a linear subjective number scale PSYCHOLOGICAL SCIENCE Brannon, E. M., Wusthoff, C. J., Gallistel, C. R., Gibbon, J. 2001; 12 (3): 238-243

    Abstract

    When humans and animals compare two numbers, responding is faster and more accurate with increasing numerical disparity and decreasing numerical size. Researchers explaining these distance and size effects often, assume that the subjective number continuum is logarithmically compressed. An alternative hypothesis is that the subjective number continuum is linear, but positions farther along it are proportionately fuzzier, that is, less precisely located. These two hypotheses have been treated as functionally equivalent because of their similar empirical predictions. The current experiment sought to resolve this issue with a paradigm originally developed to address the subjective representation of time (time left). In our adaptation, pigeons were required to compare a constant number with the number remaining after a numerical subtraction. Our results indicate that subjective number is linearly, not logarithmically, related to objective number.

    View details for Web of Science ID 000169288000009

    View details for PubMedID 11437307

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