Dr. Fiona Baumer is an Assistant Professor in the Department of Neurology, Division of Child Neurology. She is a graduate of the Stanford Human Biology program and pursued medical training at Harvard Medical School and Boston Children's Hospital. She returned to Stanford for epilepsy fellowship and now serves as an attending in child neurology. Her clinical efforts focus on caring for children with epilepsy. She has completed post-doctoral work in the labs of Dr. Robert Fisher and Dr. Amit Etkin, focusing on using transcranial magnetic stimulation paired with electroencephalography (TMS-EEG) to study brain dynamics in children with epilepsy. As a result of this work, she was awarded the K23 Mentored Patient-Oriented Research Career Development Award from the National Institute of Health.
Dr. Baumer's research focuses on understanding the impact of abnormal brain activity (called spike waves) on brain network connectivity to determine if spike waves contribute to cognitive comorbidities in children with epilepsy. Her research uses high-density EEG and TMS-EEG to study how children with epilepsy process language and to determine the impact of spike waves on this processing. The goal of her research is to determine if non-invasive stimulation techniques like TMS may be a feasible therapy to improve language, learning and cognition in this population.
- Pediatric Epilepsy
Board Certification: American Board of Psychiatry and Neurology, Neurology with Special Qualifications in Child Neurology (2015)
Residency: Boston Children's Hospital (2015) MA
Residency: Boston Children's Hospital (2012) MA
Board Certification: American Board of Psychiatry and Neurology, Epilepsy (2016)
Fellowship: Lucile Packard Children's Hospital (2016) CA
Medical Education: Harvard Medical School (2010) MA
Current Research and Scholarly Interests
Causes of Disturbed Cognition in Pediatric Epilepsy
Transcranial Magnetic Stimulation for BECTS
Benign epilepsy with centrotemporal spikes (BECTS) is the most common pediatric epilepsy syndrome. Affected children typically have a mild seizure disorder, but yet have moderate difficulties with language, learning and attention that impact quality of life more than the seizures. Separate from the seizures, these children have very frequent abnormal activity in their brain known as interictal epileptiform discharges (IEDs, or spikes), which physicians currently do not treat. These IEDs arise near the motor cortex, a region in the brain that controls movement. In this study, the investigators will use a form of non-invasive brain stimulation called transcranial magnetic stimulation (TMS) to determine the impact of IEDs on brain regions important for language to investigate: (1) if treatment of IEDs could improve language; and (2) if brain stimulation may be a treatment option for children with epilepsy. Participating children will wear electroencephalogram (EEG) caps to measure brain activity. The investigators will use TMS to stimulate the brain region where the IEDs originate to measure how this region is connected to other brain regions. Children will then receive a special form of TMS called repetitive TMS (rTMS) that briefly reduces brain excitability. The study will measure if IEDs decrease and if brain connectivity changes after rTMS is applied. The investigators hypothesize that the IEDs cause language problems by increasing connectivity between the motor cortex and language regions. The investigators further hypothesize that rTMS will reduce the frequency of IEDs and also reduce connectivity between the motor and language region
Independent Studies (6)
- Directed Reading in Neurology and Neurological Science
NENS 299 (Win)
HUMBIO 194 (Spr)
- Medical Scholars Research
NENS 370 (Sum)
- Out-of-Department Advanced Research Laboratory in Bioengineering
BIOE 191X (Aut)
- Research in Human Biology
HUMBIO 193 (Aut, Win)
- Undergraduate Research
NENS 199 (Aut, Win, Spr)
- Directed Reading in Neurology and Neurological Science
Postdoctoral Faculty Sponsor
Repetitive Transcranial Magnetic Stimulation Modulates Brain Connectivity in Children with Self-Limited Epilepsy with Centrotemporal Spikes
WILEY. 2023: S136-S137
View details for Web of Science ID 001084474200204
Connectivity increases during spikes and spike-free periods in self-limited epilepsy with centrotemporal spikes.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
OBJECTIVE: To understand the impact of interictal spikes on brain connectivity in patients with Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS).METHODS: Electroencephalograms from 56 consecutive SeLECTS patients were segmented into periods with and without spikes. Connectivity between electrodes was calculated using the weighted phase lag index. To determine if there are chronic alterations in connectivity in SeLECTS, we compared spike-free connectivity to connectivity in 65 matched controls. To understand the acute impact of spikes, we compared connectivity immediately before, during, and after spikes versus baseline, spike-free connectivity. We explored whether behavioral state, spike laterality, or antiseizure medications affected connectivity.RESULTS: Children with SeLECTS had markedly higher connectivity than controls during sleep but not wakefulness, with greatest difference in the right hemisphere. During spikes, connectivity increased globally; before and after spikes, left frontal and bicentral connectivity increased. Right hemisphere connectivity increased more during right-sided than left-sided spikes; left hemisphere connectivity was equally affected by right and left spikes.CONCLUSIONS: SeLECTS patient have persistent increased connectivity during sleep; connectivity is further elevated during the spike and perispike periods.SIGNIFICANCE: Testing whether increased connectivity impacts cognition or seizure susceptibility in SeLECTS and more severe epilepsies could help determine if spikes should be treated.
View details for DOI 10.1016/j.clinph.2022.09.015
View details for PubMedID 36307364
Association of Time to Clinical Remission With Sustained Resolution in Children With New-Onset Infantile Spasms.
BACKGROUND AND OBJECTIVE: Standard therapies (ACTH, oral steroids, or vigabatrin) fail to control infantile spasms in almost half of children. Early identification of non-responders could enable rapid initiation of sequential therapy. We aimed to determine the time to clinical remission after appropriate infantile spasms treatment initiation and identify predictors of the time to infantile spasms treatment response.METHODS: The National Infantile Spasms Consortium prospectively followed children aged 2-24 months with new onset infantile spasms at 23 US centers (2012-2018). We included children treated with standard therapy (adrenocorticotropic hormone (ACTH), oral steroids, or vigabatrin). Sustained treatment response was defined as having the last clinically recognized infantile spasms on or before treatment day 14, absence of hypsarrhythmia on EEG 2-4 weeks post-treatment, and persistence of remission to day 30. We analyzed the time to treatment response and assessed clinical characteristics to predict sustained treatment response.RESULTS: Among 395 infants, clinical infantile spasms remission occurred in 43% (n=171) within the first two weeks of treatment, of which 81% (138/171) responded within the first week of treatment. There was no difference in the median time to response across standard therapies (ACTH: median 4 days, interquartile range (IQR) 3-7; oral steroids: median 3 days, IQR 2-5; vigabatrin: median 3 days, IQR 1-6). Individuals without hypsarrhythmia on the pre-treatment EEG (i.e., abnormal but not hypsarrhythmia) were more likely to have early treatment response than infants with hypsarrhythmia at infantile spasms onset (hazard ratio 2.23, 95% confidence interval 1.39-3.57). No other clinical factors predicted early responders to therapy.CONCLUSIONS: Remission after first infantile spasms treatment can be identified by treatment day 7 in most children. Given the importance of early and effective treatment, these data suggest that children who do not respond to standard infantile spasms therapy within 1 week should be reassessed immediately for additional standard treatment. This approach could optimize outcomes by facilitating early sequential therapy for children with infantile spasms.
View details for DOI 10.1212/WNL.0000000000201232
View details for PubMedID 36038267
Inequities in therapy for infantile spasms: a call to action.
Annals of neurology
OBJECTIVE: To determine whether selection of treatment for children with infantile spasms (IS) varies by race/ethnicity.METHODS: The prospective US National Infantile Spasms Consortium database includes children with IS treated from 2012-2018. We examined the relationship between race/ethnicity and receipt of standard IS therapy (prednisolone, adrenocorticotropic hormone, vigabatrin), adjusting for demographic and clinical variables using logistic regression. Our primary outcome was treatment course, which considered therapy prescribed for the first and, when needed, the second IS treatment together.RESULTS: Of 555 children, 324 (58%) were Non-Hispanic white, 55 (10%) Non-Hispanic Black, 24 (4%) Non-Hispanic Asian, 80 (14%) Hispanic, and 72 (13%) Other/Unknown. Most (398, 72%) received a standard treatment course. Insurance type, geographic location, history of prematurity, prior seizures, developmental delay or regression, abnormal head circumference, hypsarrhythmia, and IS etiologies were associated with standard therapy. In adjusted models, Non-Hispanic Black children had lower odds of receiving a standard treatment course compared with Non-Hispanic white children (OR 0.42, 95% CI 0.20-0.89, p=0.02). Adjusted models also showed that children with public (vs. private) insurance had lower odds of receiving standard therapy for treatment 1 (OR 0.42, CI 0.21-0.84, p=0.01).INTERPRETATION: Non-Hispanic Black children were more often treated with non-standard IS therapies than Non-Hispanic white children. Likewise, children with public (vs. private) insurance were less likely to receive standard therapies. Investigating drivers of inequities, and understanding the impact of racism on treatment decisions, are critical next steps to improve care for patients with IS. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/ana.26363
View details for PubMedID 35388521
Visually sensitive seizures: An updated review by the Epilepsy Foundation.
Light flashes, patterns, or color changes can provoke seizures in up to 1 in 4000 persons. Prevalence may be higher because of selection bias. The Epilepsy Foundation reviewed light-induced seizures in 2005. Since then, images on social media, virtual reality, three-dimensional (3D) movies, and the Internet have proliferated. Hundreds of studies have explored the mechanisms and presentations of photosensitive seizures, justifying an updated review. This literature summary derives from a nonsystematic literature review via PubMed using the terms "photosensitive" and "epilepsy." The photoparoxysmal response (PPR) is an electroencephalography (EEG) phenomenon, and photosensitive seizures (PS) are seizures provoked by visual stimulation. Photosensitivity is more common in the young and in specific forms of generalized epilepsy. PS can coexist with spontaneous seizures. PS are hereditable and linked to recently identified genes. Brain imaging usually is normal, but special studies imaging white matter tracts demonstrate abnormal connectivity. Occipital cortex and connected regions are hyperexcitable in subjects with light-provoked seizures. Mechanisms remain unclear. Video games, social media clips, occasional movies, and natural stimuli can provoke PS. Virtual reality and 3D images so far appear benign unless they contain specific provocative content, for example, flashes. Images with flashes brighter than 20 candelas/m2 at 3-60 (particularly 15-20) Hz occupying at least 10 to 25% of the visual field are a risk, as are red color flashes or oscillating stripes. Equipment to assay for these characteristics is probably underutilized. Prevention of seizures includes avoiding provocative stimuli, covering one eye, wearing dark glasses, sitting at least two meters from screens, reducing contrast, and taking certain antiseizure drugs. Measurement of PPR suppression in a photosensitivity model can screen putative antiseizure drugs. Some countries regulate media to reduce risk. Visually-induced seizures remain significant public health hazards so they warrant ongoing scientific and regulatory efforts and public education.
View details for DOI 10.1111/epi.17175
View details for PubMedID 35132632
Treatment Practices and Outcomes in Continuous Spike and Wave During Slow Wave Sleep (CSWS): A Multicenter Collaboration.
The Journal of pediatrics
To determine how Continuous Spike and Wave during Slow Wave Sleep (CSWS) is currently managed and to compare the effectiveness of current treatment strategies using a database from 11 pediatric epilepsy centers in the United States.This retrospective study gathered information on baseline clinical characteristics, CSWS etiology, and treatment(s) in consecutive patients seen between 2014-2016 at 11 epilepsy referral centers. Treatments were categorized as benzodiazepines, steroids, other antiseizure medications (ASMs), or other therapies. Two measures of treatment response [clinical improvement as noted by the treating physician; and EEG improvement] were compared across therapies, controlling for baseline variables.81 children underwent 153 treatment trials during the study period (68 trials of benzodiazepines, 25 of steroids, 45 of ASMs, 14 of other therapies). Children most frequently received benzodiazepines (62%) or ASMs (27%) as first line therapy. Treatment choice did not differ based on baseline clinical variables, nor did these variables correlate with outcome. After adjusting for baseline variables, children had a greater odds of clinical improvement with benzodiazepines (OR 3.32, 95%CI 1.57-7.04, P = .002) or steroids (OR 4.04, 95%CI 1.41-11.59, p=0.01) than with ASMs and a greater odds of EEG improvement after steroids (OR 3.36, 95% CI 1.09-10.33, p=0.03) than after ASMs.Benzodiazepines and ASMs are the most frequent initial therapy prescribed for CSWS in the United States. Our data suggests that ASMs are inferior to benzodiazepines and steroids and support earlier use of these therapies. Multicenter prospective studies that rigorously assess treatment protocols and outcomes are needed.
View details for DOI 10.1016/j.jpeds.2021.01.032
View details for PubMedID 33484700
Mapping causal circuit dynamics in stroke using simultaneous electroencephalography and transcranial magnetic stimulation.
2021; 21 (1): 280
Motor impairment after stroke is due not only to direct tissue loss but also to disrupted connectivity within the motor network. Mixed results from studies attempting to enhance motor recovery with Transcranial Magnetic Stimulation (TMS) highlight the need for a better understanding of both connectivity after stroke and the impact of TMS on this connectivity. This study used TMS-EEG to map the causal information flow in the motor network of healthy adult subjects and define how stroke alters these circuits.Fourteen stroke patients and 12 controls received TMS to two sites (bilateral primary motor cortices) during two motor tasks (paretic/dominant hand movement vs. rest) while EEG measured the cortical response to TMS pulses. TMS-EEG based connectivity measurements were derived for each hemisphere and the change in connectivity (ΔC) between the two motor tasks was calculated. We analyzed if ΔC for each hemisphere differed between the stroke and control groups or across TMS sites, and whether ΔC correlated with arm function in stroke patients.Right hand movement increased connectivity in the left compared to the right hemisphere in controls, while hand movement did not significantly change connectivity in either hemisphere in stroke. Stroke patients with the largest increase in healthy hemisphere connectivity during paretic hand movement had the best arm function.TMS-EEG measurements are sensitive to movement-induced changes in brain connectivity. These measurements may characterize clinically meaningful changes in circuit dynamics after stroke, thus providing specific targets for trials of TMS in post-stroke rehabilitation.
View details for DOI 10.1186/s12883-021-02319-0
View details for PubMedID 34271872
Repetitive Transcranial Magnetic Stimulation to Assess Cortical Plasticity & Suppress Spikes in Pediatric Epilepsy
WILEY. 2020: S133
View details for Web of Science ID 000572509100209
Lacosamide-Induced Dyskinesia in Children With Intractable Epilepsy.
Journal of child neurology
Lacosamide, an antiepileptic drug prescribed for children with refractory focal epilepsy, is generally well tolerated, with dose-dependent adverse effects. We describe 4 children who developed a movement disorder in conjunction with the initiation and/or uptitration of lacosamide. Three patients developed dyskinesias involving the face or upper extremity whereas the fourth had substantial worsening of chronic facial tics. The patients all had histories suggestive of opercular dysfunction: 3 had seizure semiologies including hypersalivation, facial and upper extremity clonus while the fourth underwent resection of polymicrogyria involving the opercula. Onset, severity, and resolution of dyskinesias correlated with lacosamide dosing. These cases suggest that pediatric patients with dysfunction of the opercular cortex are at increased risk for developing drug-induced dyskinesias on high-dose lacosamide therapy. Practitioners should be aware of this potential side effect and consider weaning lacosamide or video electroencephalography (EEG) for differential diagnosis, particularly in pediatric patients with underlying opercular dysfunction.
View details for DOI 10.1177/0883073820926634
View details for PubMedID 32524876
Management of Infantile Spasms During the COVID-19 Pandemic.
Journal of child neurology
Circumstances of the COVID-19 pandemic have mandated a change to standard management of infantile spasms. On April 6, 2020, the Child Neurology Society issued an online statement of immediate recommendations to streamline diagnosis and treatment of infantile spasms with utilization of telemedicine, outpatient studies, and selection of first-line oral therapies as initial treatment. The rationale for the recommendations and specific guidance including follow-up assessment are provided in this manuscript. These recommendations are indicated as enduring if intended to outlast the pandemic, and limited if intended only for the pandemic health care crisis but may be applicable to future disruptions of health care delivery.
View details for DOI 10.1177/0883073820933739
View details for PubMedID 32576057
Crisis Standard of Care: Management of Infantile Spasms during COVID-19.
Annals of neurology
The Child Neurology Society collaborated with the Pediatric Epilepsy Research Consortium to issue an online statement April 6, 2020 of immediate recommendations to streamline diagnosis, treatment, and follow up of infantile spasms. The recommendations encourage use of telemedicine, outpatient over inpatient studies, and oral therapies as initial treatment. Each recommendation is earmarked as enduring if intended to outlast the pandemic, and limited if intended only during the duration of the pandemic. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/ana.25792
View details for PubMedID 32445204
- Emerging Applications of Noninvasive Brain Stimulation. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society 2020; 37 (2): 89
Cortical Excitability, Synaptic Plasticity, and Cognition in Benign Epilepsy With Centrotemporal Spikes: A Pilot TMS-EMG-EEG Study.
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society
2020; 37 (2): 170–80
Children with benign epilepsy with centrotemporal spikes have rare seizures emerging from the motor cortex, which they outgrow in adolescence, and additionally may have language deficits of unclear etiology. We piloted the use of transcranial magnetic stimulation paired with EMG and EEG (TMS-EMG, TMS-EEG) to test the hypotheses that net cortical excitability decreases with age and that use-dependent plasticity predicts learning.We assessed language and motor learning in 14 right-handed children with benign epilepsy with centrotemporal spikes. We quantified two TMS metrics of left motor cortex excitability: the resting motor threshold (measure of neuronal membrane excitability) and amplitude of the N100-evoked potential (an EEG measure of GABAergic tone). To test plasticity, we applied 1 Hz repetitive TMS to the motor cortex to induce long-term depression-like changes in EMG- and EEG-evoked potentials.Children with benign epilepsy with centrotemporal spikes tolerate TMS; no seizures were provoked. Resting motor threshold decreases with age but is elevated above maximal stimulator output for half the group. N100 amplitude decreases with age after controlling for resting motor threshold. Motor cortex plasticity correlates significantly with language learning and at a trend level with motor learning.Transcranial magnetic stimulation is safe and feasible for children with benign epilepsy with centrotemporal spikes, and TMS-EEG provides more reliable outcome measures than TMS-EMG in this group because many children have unmeasurably high resting motor thresholds. Net cortical excitability decreases with age, and motor cortex plasticity predicts not only motor learning but also language learning, suggesting a mechanism by which motor cortex seizures may interact with language development.
View details for DOI 10.1097/WNP.0000000000000662
View details for PubMedID 32142025
Growing identification of genetic aetiologies for neonatal-onset epilepsies: lessons from the Neonatal Seizure Registry.
Acta paediatrica (Oslo, Norway : 1992)
View details for PubMedID 30399203
Clinical and electrographic features of sunflower syndrome.
2018; 142: 58–63
Sunflower Syndrome describes reflex seizures - typically eyelid myoclonia with or without absence seizures - triggered when patients wave their hands in front of the sun. While valproate has been recognized as the best treatment for photosensitive epilepsy, many clinicians now initially treat with newer medications; the efficacy of these medications in Sunflower Syndrome has not been investigated. We reviewed all cases of Sunflower Syndrome seen at our institution over 15 years to describe the clinical course, electroencephalogram (EEG), and treatment response in these patients.Search of the electronic medical record and EEG database, as well as survey of epilepsy providers at our institution, yielded 13 cases of Sunflower Syndrome between 2002 and 2017. We reviewed the records and EEG tracings.Patients were mostly young females, with an average age of onset of 5.5 years. Seven had intellectual, attentional or academic problems. Self-induced seizures were predominantly eyelid myoclonia ± absences and 6 subjects also had spontaneous seizures. EEG demonstrated a normal background with 3-4 Hz spike waves ± polyspike waves as well as a photoparoxysmal response. Based on both clinical and EEG response, valproate was the most effective treatment for reducing or eliminating seizures and improving the EEG; 9 patients tried valproate and 66% had significant improvement or resolution of seizures. None of the nine patients on levetiracetam or seven patients on lamotrigine monotherapy achieved seizure control, though three patients had improvement with polypharmacy.Valproate monotherapy continues to be the most effective treatment for Sunflower Syndrome and should be considered early. For patients who cannot tolerate valproate, higher doses of lamotrigine or polypharmacy should be considered. Levetiracetam monotherapy, even at high doses, is unlikely to be effective.
View details for PubMedID 29555355
Refractory focal epilepsy in a paediatric patient with primary familial brain calcification.
2018; 56: 50–52
Primary familial brain calcification (PFBC), otherwise known as Fahr's disease, is a rare autosomal dominant condition with manifestations of movement disorders, neuropsychiatric symptoms, and epilepsy in a minority of PFBC patients. The clinical presentation of epilepsy in PFBC has not been described in detail. We present a paediatric patient with PFBC and refractory focal epilepsy based on seizure semiology and ictal EEG, but with generalized interictal EEG abnormalities. The patient was found to have a SLC20A2 mutation known to be pathogenic in PFBC, as well as a variant of unknown significance in SCN2A. This case demonstrates that the ictal EEG is important for accurately classifying epilepsy in affected subjects with PFBC. Further, epilepsy in PFBC may be a polygenic disorder.
View details for PubMedID 29448117
Language Dysfunction in Pediatric Epilepsy.
The Journal of pediatrics
2018; 194: 13–21
View details for PubMedID 29241678
Systemic Manifestations in Pyridox(am)ine Phosphate Oxidase (PNPO) Deficiency
View details for DOI 10.1016/j.pediatrneurol.2017.05.024
Corpus Callosum White Matter Diffusivity Reflects Cumulative Neurological Comorbidity in Tuberous Sclerosis Complex.
Neurological manifestations in Tuberous Sclerosis Complex (TSC) are highly variable. Diffusion tensor imaging (DTI) may reflect the neurological disease burden. We analyzed the association of autism spectrum disorder (ASD), intellectual disability (ID) and epilepsy with callosal DTI metrics in subjects with and without TSC.186 children underwent 3T MRI DTI: 51 with TSC (19 with concurrent ASD), 46 with non-syndromic ASD and 89 healthy controls (HC). Subgroups were based on presence of TSC, ASD, ID, and epilepsy. Density-weighted DTI metrics obtained from tractography of the corpus callosum were fitted using a 2-parameter growth model. We estimated distributions using bootstrapping and calculated half-life and asymptote of the fitted curves.TSC was associated with a lower callosal fractional anisotropy (FA) than ASD, and ASD with a lower FA than HC. ID, epilepsy and ASD diagnosis were each associated with lower FA values, demonstrating additive effects. In TSC, the largest change in FA was related to a comorbid diagnosis of ASD. Mean diffusivity (MD) showed an inverse relationship to FA. Some subgroups were too small for reliable data fitting.Using a cross-disorder approach, this study demonstrates cumulative abnormality of callosal white matter diffusion with increasing neurological comorbidity.
View details for DOI 10.1093/cercor/bhx247
View details for PubMedCentralID PMC6132277
- Quinidine-associated skin discoloration in KCNT1-associated pediatric epilepsy. Neurology 2017; 89 (21): 2212
Diagnosis of adenylosuccinate lyase deficiency by metabolomic profiling in plasma reveals a phenotypic spectrum.
Molecular genetics and metabolism reports
2016; 8: 61-66
Adenylosuccinate lyase (ADSL) deficiency is a rare autosomal recessive neurometabolic disorder that presents with a broad-spectrum of neurological and physiological symptoms. The ADSL gene produces an enzyme with binary molecular roles in de novo purine synthesis and purine nucleotide recycling. The biochemical phenotype of ADSL deficiency, accumulation of SAICAr and succinyladenosine (S-Ado) in biofluids of affected individuals, serves as the traditional target for diagnosis with targeted quantitative urine purine analysis employed as the predominate method of detection. In this study, we report the diagnosis of ADSL deficiency using an alternative method, untargeted metabolomic profiling, an analytical scheme capable of generating semi-quantitative z-score values for over 1000 unique compounds in a single analysis of a specimen. Using this method to analyze plasma, we diagnosed ADSL deficiency in four patients and confirmed these findings with targeted quantitative biochemical analysis and molecular genetic testing. ADSL deficiency is part of a large a group of neurometabolic disorders, with a wide range of severity and sharing a broad differential diagnosis. This phenotypic similarity among these many inborn errors of metabolism (IEMs) has classically stood as a hurdle in their initial diagnosis and subsequent treatment. The findings presented here demonstrate the clinical utility of metabolomic profiling in the diagnosis of ADSL deficiency and highlights the potential of this technology in the diagnostic evaluation of individuals with neurologic phenotypes.
View details for DOI 10.1016/j.ymgmr.2016.07.007
View details for PubMedID 27504266
View details for PubMedCentralID PMC4969260
A 10-Month-Old With Intermittent Hypotonia and Paralysis
2016; 138 (1)
A 10-month-old boy presented with a 1-day history of flaccid quadriplegia and dysconjugate gaze. His history was remarkable for stereotyped episodes of flaccid quadriplegia or hemiplegia, oculomotor abnormalities, and limb or neck posturing, beginning in the first days of life and becoming more frequent and more prolonged over time. The patient was healthy and developmentally normal between episodes. Results of extensive laboratory evaluations, including EEG and brain imaging studies, were negative. The patient's history, diagnostic evaluation, and final diagnosis are reviewed. This case illustrates the importance of a fundamental understanding of neurologic localization in pediatric care and a focused diagnostic approach to an infant with paroxysmal neurologic signs.
View details for DOI 10.1542/peds.2015-1896
View details for Web of Science ID 000378853100004
View details for PubMedID 27252036
Fatal Central Nervous System Disease Following First Infliximab Infusion in a Child With Inflammatory Bowel Disease
2016; 57: 91-94
Infliximab is used in the treatment of inflammatory bowel disease. Previously reported neurological complications include central and peripheral demyelinating disorders and neuropathies occurring months into therapy.A seven-year-old boy diagnosed with ulcerative colitis and primary sclerosing cholangitis received infliximab. Six hours following his uneventful infusion, he awoke with headache and emesis and rapidly became obtunded. Neurological examination revealed minimally reactive pupils and otherwise absent brainstem reflexes. Cranial computed tomography revealed hypodense lesions in the cerebral hemispheres, cerebellum, and pons accompanied by hemorrhage. Magnetic resonance imaging showed diffusion restriction concerning for ischemia with areas of ring enhancement suggestive of inflammation. Vessel imaging was normal, and cerebrospinal fluid and serum studies showed only an extremely elevated level of d-dimer. Echocardiogram showed depressed ventricular function but neither intracardiac shunt nor thrombus. Within four days he met criteria for brain death. Autopsy was refused.This is the first report of a fulminant, fatal central nervous system process to occur after an initial dose of infliximab. The differential diagnosis includes multifocal arterial strokes and a devastating demyelinating process.
View details for DOI 10.1016/j.pediatrneurol.2015.12.017
View details for Web of Science ID 000373522800018
View details for PubMedID 26831951
SCN2A-Related Early-Onset Epileptic Encephalopathy Responsive to Phenobarbital.
Journal of pediatric epilepsy
2016; 5 (1): 42-46
Voltage-gated sodium channels (Nav) are critical regulators of neuronal excitability. Genes for the α-subunits of three sodium channel subtypes-SCN1A, SCN2A, and SCN3A-are all located on chromosome 2q24. A full-term boy with an unremarkable birth history presented at 1 month of age with unusual movements that had started on day of life 2. Exam was notable for lack of visual attention, hypotonia, and hyperreflexia. Electroencephalogram (EEG) showed an invariant burst suppression with multifocal spikes, ictal episodes with bicycling movements associated with buildups of rhythmic activity, and epileptic spasms. Work-up revealed a 1.77-Mb duplication at locus 2q24.3, encompassing the entirety of SCN2A and SCN3A, but not SCN1A. Phenobarbital led to rapid resolution of the clinical seizures and EEG background normalized other than rare sharp waves. Early-onset epileptic encephalopathy (EOEE), with neonatal seizures, burst suppression, and reversibility with phenobarbital, is part of the enlarging spectrum of Nav channelopathies. The delayed diagnosis provided an unusual opportunity to view the early natural history of this disorder and its remarkable responsiveness to barbiturate therapy. The clinical and EEG response to phenobarbital implicates seizures as the cause of the encephalopathy.
View details for PubMedID 27595042
View details for PubMedCentralID PMC5004990
Longitudinal Changes in Diffusion Properties in White Matter Pathways of Children With Tuberous Sclerosis Complex
2015; 52 (6): 615-623
Abnormal white matter development in patients with tuberous sclerosis complex, a multisystem hamartomatous disorder caused by aberrant neural proliferation and axonal maturation, may be associated with poorer neurocognitive outcomes. The purpose of this study is to identify predictors of longitudinal changes in diffusion properties of white matter tracts in patients with tuberous sclerosis complex.Diffusion magnetic resonance imaging was carried out in 17 subjects with tuberous sclerosis complex (mean age, 7.2 ± 4.4 years) with at least two magnetic resonance imaging scans (mean number of days between scans, 419.4 ± 105.4). There were 10 males; 5 of 17 had autism spectrum disorder and 10 of 17 had epilepsy. Regions of interest were placed to delineate the internal capsule/corona radiata, cingulum, and corpus callosum. The outcomes were mean change in apparent diffusion coefficient and fractional anisotropy. Data were analyzed using Pearson's correlation and multiple linear regression analyses.Gender was a significant predictor of mean change in apparent diffusion coefficient in the left internal capsule, right and left cingulum bundles, and corpus callosum and a significant predictor of mean change in fractional anisotropy in the corpus callosum. Epilepsy was a significant predictor of mean change in apparent diffusion coefficient in the left internal capsule. Autism spectrum disorder was not predictive of diffusion changes in any of the studied pathways.Clinical variables, including gender and epilepsy, have an effect on the development of white matter pathways. These variables should be taken into consideration when counseling tuberous sclerosis complex patients and in future imaging studies in this population.
View details for DOI 10.1016/j.pediatrneurol.2015.02.004
View details for Web of Science ID 000355572500007
View details for PubMedID 25817702
View details for PubMedCentralID PMC4442035
- Teaching Video NeuroImages: Nonepileptic myoclonus in a neonate following severe hypoxic-ischemic injury NEUROLOGY 2015; 84 (12): E90-E90
Neuromyelitis Optica in an Adolescent After Bone Marrow Transplantation
2015; 52 (1): 119-124
Central nervous system complications of bone marrow transplant are a common occurrence and the differential diagnosis is quite broad, including opportunistic infections, medications toxicities, graft versus host disease, and other autoimmune processes.We summarize previously reported cases of autoimmune myelitis in post-transplant patients and discuss a 17-year-old boy who presented with seronegative neuromyelitis optica after a bone marrow transplant for acute myeloid leukemia. Our patient had a marked improvement in symptoms after plasmapheresis.Including our patient, there have been at least eight cases of post-transplant autoimmune myelitis presented in the literature, and at least three of these are suspicious for neuromyelitis optica. Several of these patients had poor outcomes with persistent symptoms after the myelitis. Autoimmune processes such as neuromyelitis optica should be carefully considered in patients after transplant as aggressive treatment like early plasmapheresis may improve outcomes.
View details for DOI 10.1016/j.pediatrneurol.2014.07.007
View details for Web of Science ID 000348411800019
View details for PubMedID 25444090
Normative Apparent Diffusion Coefficient Values in the Developing Fetal Brain
AMERICAN JOURNAL OF NEURORADIOLOGY
2009; 30 (9): 1799-1803
Previous studies of diffusion-weighted imaging (DWI) in fetuses are limited. Because of the need for normative data for comparison with young fetuses and preterm neonates with suspected brain abnormalities, we studied apparent diffusion coefficient (ADC) values in a population of singleton, nonsedated, healthy fetuses.DWI was performed in 28 singleton nonsedated fetuses with normal or questionably abnormal results on sonography and normal fetal MR imaging results; 10 fetuses also had a second fetal MR imaging, which included DWI. ADC values in the periatrial white matter (WM), frontal WM, thalamus, basal ganglia, cerebellum, and pons were plotted against gestational age and analyzed with linear regression. We compared mean ADC in different regions using the Tukey Honestly Significant Difference test. We also compared rates of decline in ADC with increasing gestational age across different areas by using the t test with multiple comparisons correction. Neurodevelopmental outcome was assessed.Median gestational age was 24.28 weeks (range, 21-33.43 weeks). Results of all fetal MR imaging examinations were normal, including 1 fetus with a normal variant of a cavum velum interpositum. ADC values were highest in the frontal and periatrial WM and lowest in the thalamus and pons. ADC declined with increasing gestational age in periatrial WM (P = .0003), thalamus (P < .0001), basal ganglia (P = .0035), cerebellum (P < .0001), and pons (P = .024). Frontal WM ADC did not significantly change with gestational age. ADC declined fastest in the cerebellum, followed by the thalamus.Regional differences in nonsedated fetal ADC values and their evolution with gestational age likely reflect differences in brain maturation and are similar to published data in premature neonates.
View details for DOI 10.3174/ajnr.A1661
View details for Web of Science ID 000271031300033
View details for PubMedID 19556350
View details for PubMedCentralID PMC4524324
Fast 3D H-1 MRSI of the Corticospinal Tract in Pediatric Brain
JOURNAL OF MAGNETIC RESONANCE IMAGING
2009; 29 (1): 1-6
To develop a (1)H magnetic resonance spectroscopic imaging (MRSI) sequence that can be used to image infants/children at 3T and by combining it with diffusion tensor imaging (DTI) tractography, extract relevant metabolic information corresponding to the corticospinal tract (CST).A fast 3D MRSI sequence was developed for pediatric neuroimaging at 3T using spiral k-space readout and dual band RF pulses (32 x 32 x 8 cm field of view [FOV], 1 cc iso-resolution, TR/TE = 1500/130, 6:24 minute scan). Using DTI tractography to identify the motor tracts, spectra were extracted from the CSTs and quantified. Initial data from infants/children with suspected motor delay (n = 5) and age-matched controls (n = 3) were collected and N-acetylaspartate (NAA) ratios were quantified.The average signal-to-noise ratio of the NAA peak from the studies was approximately 22. Metabolite profiles were successfully acquired from the CST by using DTI tractography. Decreased NAA ratios in those with motor delay compared to controls of approximately 10% at the CST were observed.A fast and robust 3D MRSI technique targeted for pediatric neuroimaging has been developed. By combining with DTI tractography, metabolic information from the CSTs can be retrieved and estimated. By combining DTI and 3D MRSI, spectral information from various tracts can be obtained and processed.
View details for DOI 10.1002/jmri.21394
View details for Web of Science ID 000262168200001
View details for PubMedID 19097091
View details for PubMedCentralID PMC2832220
A pilot study of antidepressant-induced mania in pediatric bipolar disorder: Characteristics, risk factors, and the serotonin transporter gene
Conference on Pediatric Bipolar Disorder
ELSEVIER SCIENCE INC. 2006: 1005–12
Antidepressant-induced mania (AIM) has been described in bipolar disorder (BD) and has been associated with the short-allele of the serotonin transporter gene (5-HTT). We wished to investigate the frequency of and risk factors for AIM in pediatric patients with or at high risk for BD.Fifty-two children and adolescents (30 with BD and 22 with subthreshold manic symptoms, 15.1 +/- 3.4 years old), all with a parent with BD, were interviewed with their parents for manic/depressive symptoms occurring before and after past antidepressant treatment. The 47 subjects with serotonin reuptake inhibitor (SSRI) exposure were genotyped for the 5-HTT polymorphism.Fifty percent of subjects were AIM+ and 25.5% had new onset of suicidal ideation. The AIM+ and AIM- groups did not differ significantly in relation to allele (p = .36) or genotype (p = .53) frequencies of the 5-HTT polymorphism. The AIM+ subjects were more likely to have more comorbidities (3.2 vs. 2.4; p = .02) and be BD type I (p = .04) than AIM- subjects.Youth with or at high risk for BD may be particularly vulnerable to SSRI AIM and thus should be monitored if given SSRIs. In this preliminary study, we did not find that the 5-HTT polymorphism significantly influenced vulnerability to AIM.
View details for DOI 10.1016/j.biopsych.2006.06.010
View details for PubMedID 16945343
- A pilot study of antidepressant-induced mania in pediatric bipolar disorder: Characteristics, risk factors, and the serotonin transporter gene. Biological Psychiatry 2006; 60 (9): 1005-12
Mercaptoacetate induces feeding through central opioid-mediated mechanisms in rats
2000; 864 (2): 240-251
The endogenous opioid system has been implicated in the mediation of food intake elicited by such regulatory challenges as glucoprivation induced by 2-deoxy-D-glucose (2DG) or food deprivation in rodents. Administration of the free fatty acid oxidation inhibitor, mercaptoacetate (MA), produces a potent short-term increase in feeding in rats, the mechanisms of which have been dissociated from that elicited by 2DG. The present study evaluated whether MA-induced feeding in rats was mediated by the endogenous opioid system through systemic administration of the general opioid antagonist, naltrexone, through central administration of either general, mu, mu(1), kappa(1) or delta opioid antagonists, and through central administration of antisense oligodeoxynucleotide (AS ODN) probes directed against specific exons of either the mu (MOR-1), kappa (KOR-1), kappa(3) (KOR-3/ORL-1) or delta (DOR-1) opioid receptor clones. MA-induced feeding was significantly and dose-dependently reduced by systemic naltrexone (0.005-5 mg/kg); these ingestive effects were quite selective since neither total, ambulatory nor stereotypic activity was affected by either MA itself or MA paired with naltrexone. MA-induced feeding was significantly reduced by central pretreatment with either naltrexone (0.1-20 microgram) or mu-selective (beta-funaltrexamine, 0.1-20 microgram), mu(1)-selective (naloxonazine, 1-20 microgram), kappa(1)-selective (nor-binaltorphamine, 0.1-20 microgram), or delta-selective (naltrindole, 1-20 microgram) opioid receptor antagonists. MA-induced feeding was significantly reduced by AS ODN probes directed against either exons 1, 2 or 3, but not exon 4 of the MOR-1 clone, exon 3, but not exons 1 or 2 of the KOR-1 clone, exons 1 or 2, but not exon 3 of the KOR-3/ORL-1 clone, and exon 1, but not exons 2 or 3 of the DOR-1 clone. These data are discussed in terms of opioid mediation of ingestive responses related to fat, and in terms of potential central sites of action at which lipoprivic ingestive responses might act.
View details for Web of Science ID 000087003000009
View details for PubMedID 10802031