Elaine Wirrell

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (174)523.24 Total impact

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    ABSTRACT: Objective: Infantile spasms are seizures associated with a severe epileptic encephalopathy presenting in the first 2 years of life, and optimal treatment continues to be debated. This study evaluates early and sustained response to initial treatments and addresses both clinical remission and electrographic resolution of hypsarhythmia. Secondarily, it assesses whether response to treatment differs by etiology or developmental status. Methods: The National Infantile Spasms Consortium established a multi-center, prospective database enrolling infants with new diagnosis of infantile spasms. Children were considered responders if there was clinical remission and resolution of hypsarhythmia that was sustained at three months after first treatment initiation. Standard treatments of ACTH, oral corticosteroids, and vigabatrin were considered individually, and all other non-standard therapies were analyzed collectively. Developmental status and etiology were assessed. We compared response rates by treatment group using Chi-square tests and multivariable logistic regression models. Results: Two hundred and thirty infants were enrolled from 22 centers. Overall, 46% of children receiving standard therapy responded compared to only 9% who responded to non-standard therapy (p<0.001). 55% of infants receiving ACTH as initial treatment responded, compared to 39% for oral corticosteroids, 36% for vigabatrin, and 9% for other (p<0.001). Neither etiology nor development significantly modified the response pattern by treatment group. Interpretation: Response rate varies by treatment choice. Standard therapies should be considered as initial treatment for infantile spasms, including those with impaired development or known structural or genetic/metabolic etiology. ACTH appeared to be more effective than other standard therapies. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · Annals of Neurology
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    K. Nickels · L.C. Wong-Kisiel · E.T. Payne · E.C. Wirrell

    Preview · Article · Oct 2015
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    Preview · Article · Oct 2015
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    ABSTRACT: Epilepsy is common in people with intellectual and developmental disabilities (IDD). In adulthood, patients with IDD and epilepsy (IDD-E) have neurologic, psychiatric, medical, and social challenges compounded by fragmented and limited care. With increasing neurologic disability, there is a higher frequency of epilepsy, especially symptomatic generalized and treatment-resistant epilepsies. The causes of IDD-E are increasingly recognized to be genetic based on chromosomal microarray analysis to identify copy number variants, gene panels (epilepsy, autism spectrum disorder, intellectual disability), and whole-exome sequencing. A specific genetic diagnosis may guide care by pointing to comorbid disorders and best therapy. Therapy to control seizures should be individualized, with drug selection based on seizure types, epilepsy syndrome, concomitant medications, and comorbid disorders. There are limited comparative antiepileptic drug data in the IDD-E population. Vagus nerve and responsive neural stimulation therapies and resective surgery should be considered. Among the many comorbid disorders that affect patients with IDD-E, psychiatric and sleep disorders are common but often unrecognized and typically not treated. Transition from holistic and coordinated pediatric to adult care is often a vulnerable period. Communication among adult health care providers is complex but essential to ensure best care when these patients are seen in outpatient, emergency room, and inpatient settings. We propose specific recommendations for minimum care standards for people with IDD-E.
    Full-text · Article · Oct 2015 · Neurology
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    ABSTRACT: Objective: We evaluated the temporal course of seizure outcome in children with pathology-confirmed focal cortical dysplasia and explored predictors of sustained seizure freedom. Methods: We performed a single-center retrospective study of children ≤18 years who underwent resective surgery from January 1, 2000 through December 31, 2012 and had pathology-proven focal cortical dysplasia. Surgical outcome was classified as seizure freedom (Engel class I) or seizure recurrence (Engel classes II-IV). Fisher exact and nonparametric Wilcoxon ranksum tests were used, as appropriate. Survival analysis was based on seizure-free outcome. Patients were censored at the time of seizure recurrence or seizure freedom at last follow-up. Results: Thirty-eight patients were identified (median age at surgery, 6.5 years; median duration of epilepsy, 3.3 years). Median time to last follow-up was 13.5 months (interquartile range, 7-41 months). Twenty patients (53%) were seizure free and 26 patients (68%) attained seizure freedom for a minimum of 3 months. Median time to seizure recurrence was 38 months (95% confidence interval, 6-109 months), and the cumulative seizure-free rate was 60% at 12 months (95% confidence interval, 43%-77%). Clinical features associated with seizure freedom at last follow-up included older age at seizure onset (P = .02), older age at surgery (P = .04), absent to mild intellectual disability before surgery (P = .05), and seizure freedom for a minimum of 3 months (P < .001). Conclusion: Favorable clinical features associated with sustained seizure freedom included older age at seizure onset, older age at surgery, absent or mild intellectual disability at baseline, and seizure freedom for a minimum of 3 months.
    Full-text · Article · Sep 2015 · Pediatric Neurology
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    ABSTRACT: Electrical status epilepticus in slow-wave sleep (ESES) is characterized by nearly continuous spike-wave discharges during non-rapid eye movement (REM) sleep. ESES is present in Landau-Kleffner syndrome (LKS) and continuous spike and wave in slow-wave sleep (CSWS). Sulthiame has demonstrated reduction in spike-wave index (SWI) in ESES, but is not available in the United States. Acetazolamide (AZM) is readily available and has similar pharmacologic properties. Our aims were to assess the effect of AZM on SWI and clinical response in children with LKS and CSWS. Children with LKS or CSWS treated with AZM at our institution were identified retrospectively. Pre- and posttherapy electroencephalography (EEG) studies were evaluated for SWI. Parental and teacher report of clinical improvement was recorded. Six children met criteria for inclusion. Three children (50%) demonstrated complete resolution or SWI <5% after AZM. All children had improvement in clinical seizures and subjective improvement in communication skills and school performance. Five of six children had subjective improvement in hyperactivity and attention. AZM is a potentially effective therapy for children with LKS and CSWS. This study lends to the knowledge of potential therapies that can be used for these disorders, which can be challenging for families and providers. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
    No preview · Article · Jul 2015 · Epilepsia
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    ABSTRACT: One challenge for families whose children are undergoing presurgical evaluation for epilepsy surgery is the unpredictable length of hospitalization for video-electroencephalograph monitoring. The goal of this study was to retrospectively evaluate length of stay in children admitted for presurgical evaluation at a tertiary referral center. Duration of stay for children with medically intractable epilepsy admitted for presurgical evaluation to the Pediatric Epilepsy Monitoring Unit at Mayo Clinic Rochester between 2010 and 2013 was evaluated retrospectively. Of 140 children, surgical candidacy was determined in 122 (87.1%) (72 candidates, 50 noncandidates). The mean length of stay was 4.0 ± 3.7 days and was not predicted by candidacy for surgery, age at monitoring, duration of epilepsy, number of antiepileptic drugs at admission, or focal/hemispheric magnetic resonance imaging abnormality. Shorter length of stay was predicted by younger age at epilepsy onset (P < 0.05) and shorter interval since most recent seizure (P = 0.001). Subtraction ictal single-photon emission computed tomography coregistered to magnetic resonance imaging was performed in 43 (35.2%) children, and correlated with longer length of stay (mean 5.1 ± 4.1 days for subtraction ictal single-photon emission computed tomography coregistered to magnetic resonance imaging users versus 3.5 ± 3.3 days for nonusers, P = 0.022). Antiepileptic drugs were reduced either upon or after admission in 67 (54.9%) children, and the length of stay was significantly longer in these patients (mean 5.5 ± 4.1 days if antiepileptic drugs were reduced versus 2.2 ± 2.1 days if not reduced, P < 0.001). Significant predictors of shorter length of stay include younger age at epilepsy onset, shorter interval from most recent seizure, lack of subtraction ictal single-photon emission computed tomography coregistered to magnetic resonance imaging, and lack of need for AED reduction on or after admission. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jun 2015 · Pediatric Neurology
  • Charuta Joshi · Anne T Berg · Elaine Wirrell
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    ABSTRACT: We aimed to determine variation in treatment of newly diagnosed infantile spasms, focusing on details of adrenocorticotropic hormone (ACTH) administration using a Redcap questionnaire sent to members of the Child Neurology Society. Two hundred fifty-seven members responded. Eighty-four percent prescribers used ACTH to treat infantile spasms. Seventy-six percent always admit patients. There is no difference between prescriber type (epileptologist or other) and prescriber location (state-funded or non-state-funded hospital) for decision to admit. Electroencephalographic (EEG) confirmation of spasms and education for injection were the commonest reasons to admit. Only 45% of prescribers accurately estimated the cost of ACTH. Participants in the hospital vial program were significantly more likely to always admit patients for ACTH than those who did not participate in such a program (P = .02). Although having the hospital sample vial allows time to complete investigation of infantile spasms and eliminates delays in initiating ACTH, it adds significantly to the cost of therapy. © The Author(s) 2015.
    No preview · Article · May 2015 · Journal of child neurology
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    ABSTRACT: Objective Infantile spasms (IS) are a severe form of childhood epilepsy associated with autism spectrum disorders (ASD) in up to 35% of cases. The objective of this post hoc analysis of our randomized control trial was to determine whether rapid diagnosis and treatment of IS could limit the incidence of ASD while identifying risk factors related to ASD outcome.Methods Patients with IS were randomized in a standardized diagnostic and treatment protocol. Clinical and electroencephalogram (EEG) evaluations were completed at all eight visits over 5 years, while cognitive evaluations were administered at 0, 6, 24 and 60 months, respectively. Autism was initially screened by means of the Checklist for Autism in Toddlers (CHAT) at 24 months, and formally assessed at the 30-and 60-month follow-ups using the Autism Diagnostic Observation Schedule—Generic (ADOS-G).ResultsOf the 69 patients included in the study, 25 could not be assessed due to severe delay or death. Eleven of the 42 patients screened with CHAT, were found to be at risk of an ASD outcome. ADOS was performed in 44 and 10 were diagnosed with ASD. The CHAT proved to correlate highly with the ADOS (80% ppv). Only patients with symptomatic IS developed ASD (p = 0.003). Earlier diagnosis or successful treatment did not correlate with a reduced rate of ASD. Other risk factors were identified such as having chronic epileptic discharges in the frontotemporal areas after disappearance of hypsarrhythmia (p = 0.005 and p = 0.007) and being of nonwhite origin (p = 0.009).SignificanceASD was only observed in children with sympyomatic IS. Other clinical risk factors include chronic frontotemporal epileptic activity and being of non-white origin. Early diagnosis and treatment did not prevent ASD as an outcome of IS. However, patients at risk for ASD could be identified early on and should in the future benefit from early intervention to potentially improve their long-term outcome.
    Full-text · Article · May 2015 · Epilepsia
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    ABSTRACT: OBJECT Resection can sometimes offer the best chance of meaningful seizure reduction in children with medically intractable epilepsy. However, when surgery fails to achieve the desired outcome, reoperation may be an option. The authors sought to investigate outcomes following resective reoperation in pediatric patients with refractory epilepsy, excluding tumoral epilepsies. Differences in preoperative workup between surgeries are analyzed to identify factors influencing outcomes and complications in this complex group. METHODS Medical records were reviewed for all pediatric patients undergoing a repeat resective surgery for refractory epilepsy at the authors' institution between 2005 and 2012. Tumor and vascular etiologies were excluded. Preoperative evaluation and outcomes were analyzed for each surgery and compared. RESULTS Ten patients met all inclusion criteria. The median age at seizure onset was 4.5 months. Preoperative MRI revealed no lesion in 30%. Nonspecific gliosis and cortical dysplasia were the most common pathologies. The majority of preoperative workups included MRI, video-electroencephalography (EEG), and SISCOM. Intracranial EEG was performed for 60% for the first presurgical evaluation and 70% for the second evaluation. The goal of surgery was palliative in 4 patients with widespread cortical dysplasia. The final Engel outcome was Class I in 50%. The rate of favorable outcome (Engel Class I-II) was 70%. The complication rate for the initial surgery was 10%. However, the rate increased to 50% with the second surgery, and 3 of these 5 complications were pseudomeningoceles requiring shunt placement (2 of the 3 patients underwent hemispherotomy). CONCLUSIONS Resective reoperation for pediatric refractory epilepsy has a high rate of favorable outcome and should be considered in appropriate candidates, even as a palliative measure. Intracranial EEG monitoring should be considered on initial workup in cases where the results of imaging or EEG studies are ambiguous or conflicting. Epilepsy secondary to cortical dysplasia, especially if the dysplasia is not seen clearly on MRI, can be difficult to cure surgically. Therefore, in these cases, as large a resection as can be safely accomplished should be done, particularly when the goal is palliative. The rate of complications, particularly pseudomeningocele ultimately requiring shunt placement, is much higher following reoperation, and patients should be counseled accordingly.
    No preview · Article · Apr 2015 · Journal of Neurosurgery Pediatrics
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    ABSTRACT: To prospectively evaluate the etiology of new-onset infantile spasms and evaluate the yield of genetic and metabolic investigations in those without obvious cause after initial clinical evaluation and magnetic resonance imaging (MRI). Twenty-one U.S. pediatric epilepsy centers prospectively enrolled infants with newly diagnosed West syndrome in a central database. Etiology and investigations performed within 3 months of diagnosis were documented. From June 2012 to June 2014, a total of 251 infants were enrolled (53% male). A cause was identified in 161 (64.4%) of 250 cases (genetic,14.4%; genetic-structural, 10.0%; structural-congenital, 10.8%; structural-acquired, 22.4%; metabolic, 4.8%; and infectious, 2.0%). An obvious cause was found after initial clinical assessment (history and physical examination) and/or MRI in 138 of 161, whereas further genetic and metabolic studies were revealing in another 23 cases. Of 112 subjects without an obvious cause after initial evaluation and MRI, 81 (72.3%) had undergone genetic testing, which showed a causal abnormality in 23.5% and a variant of unknown significance in 14.8%. Although metabolic studies were done in the majority (serum, 79.5%; urine, 69.6%; and cerebrospinal fluid [CSF], 38.4%), these revealed an etiology in only five cases (4.5%). No correlation was found between type of health insurance (public vs. private) and either genetic or metabolic testing. Clinical evaluation and MRI provide a specific diagnosis in 55% of children presenting with West syndrome. We propose that a cost-effective workup for those without obvious cause after initial clinical evaluation and MRI includes an array comparative genomic hybridization (aCGH) followed by an epilepsy gene panel if the microarray is not definitive, serum lactate, serum amino acids, and urine organic acids. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
    No preview · Article · Mar 2015 · Epilepsia
  • Umut Aypar · Elaine C. Wirrell · Nicole L. Hoppman

    No preview · Article · Mar 2015 · American Journal of Medical Genetics Part A
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    ABSTRACT: The aim of this study was to identify preadmission variables that are prognostic of epilepsy surgical candidacy for children admitted into an epilepsy-monitoring unit. This study is a retrospective review of patients 0-18 years who were admitted into the pediatric epilepsy-monitoring unit at Mayo Clinic between November 2010 and December 2013 to assess for surgery candidacy for medically intractable epilepsy. Demographic data, epilepsy details, treatments, electroencephalograph and imaging results, and the consensus notes of the epilepsy surgery conferences were collected. One hundred and forty eight children underwent inpatient, prolonged video-electroencephalograph monitoring for presurgical evaluation, of which 136 had their typical events recorded. Five recommended for callosotomy alone were excluded and 131 composed the study group. Of these 131, the epilepsy surgery conference consensus deemed that 69 were surgical candidates, of which 45 (65%) underwent resective surgery. Chi-square analysis found seven preadmission predictors of surgical candidacy: single semiology at seizure onset (P < 0.001), structural etiology (P < 0.001), one or more interictal foci all in the same hemisphere (P < 0.004), focal background electroencephalograph slowing (P < 0.001), focal or hemispheric abnormality on magnetic resonance imaging (P < 0.001), male sex (P = 0.02), and normal development (P = 0.04). The presence of fewer than four predictors was suggestive of low likelihood of candidacy (<31%), whereas if more than four factors were present, 91% were found to be surgical candidates. These findings facilitate clinical decision-making for providers in a cost-effective manner and provide realistic expectations for families. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · Pediatric Neurology
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    ABSTRACT: Objective: To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels. Methods: Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay. Results: Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13-75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients. Conclusions: DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.
    No preview · Article · Oct 2014 · Neurology
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    ABSTRACT: Objective: To determine the outcome of implanting fewer electrodes over the hemisphere with less supporting presurgical localizing data. Methods: We retrospectively reviewed our epilepsy surgery database at Mayo Clinic, Rochester, Minnesota, between January 1, 1999, and December 31, 2011, to identify patients who had an asymmetric number of electrode contacts implanted in each hemisphere for seizure localization. We scored each presurgical noninvasive data point (0, 0.5, or 1) to predict the likelihood of identifying seizure onset in the hemisphere with fewer intracranial electrode contacts (HFEC). An aggregate score was obtained for each patient. Results: Thirteen (37%) of 35 patients had HFEC-onset seizures on intracranial electroencephalography (iEEG). The following factors predicted HFEC-onset seizures: (1) temporal lobe epilepsy (p = 0.02); (2) interictal scalp electroencephalographic discharges at the HFEC (p = 0.04); and (3) both interictal and ictal scalp EEG discharges at the HFEC (p = 0.01). The median (range) aggregate score was 2 (1-3) for patients with HFEC-onset seizures recorded on iEEG and 1 (0-3) for patients without HFEC-onset seizures (p = 0.001). Using this scoring model, the odds ratio of identifying HFEC-onset seizures on iEEG was 6.4 for each one-point increment in the aggregate score. The area under the receiver operating characteristic curve for this model was 0.84, suggesting excellent ability of the aggregate score to discriminate between patients with and without HFEC-onset seizures on iEEG. Significance: Implanting electrodes on the basis of limited supporting presurgical data may be useful in selected patients, especially those with temporal lobe epilepsy, interictal scalp discharges involving the HFEC, or both interictal and ictal scalp discharges involving the HFEC. In addition, our proposed scoring system may be helpful in selecting patients with complicated epilepsy for implantation of an asymmetric number of intracranial electrodes in the hemispheres.
    Full-text · Article · Sep 2014 · Epilepsia
  • Carol S Camfield · Anne Berg · Ulrich Stephani · Elaine C Wirrell
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    ABSTRACT: This chapter covers the syndromes of benign epilepsy with centrotemporal spikes (BECTS), nonlesional focal epilepsy in otherwise normal children (NLFN), and the genetic generalized epilepsies. BECTS is an epilepsy syndrome that always enters terminal remission before the general age of a planned transition of adolescents. This is also the case for the majority (65%) of those with childhood absence epilepsy (CAE). Approximately 15% of patients with CAE who initially remit during their childhood years later develop juvenile myoclonic epilepsy (JME) as teenagers. They will have many issues for continuing medical care and transition, because their seizure disorder generally persists into adulthood. A significant minority of NLFN (~35%) and most patients with JME continue to have active epilepsy into adulthood. In addition, CAE, JME, and NLFN patients are at risk of a number of significant adverse social outcomes that require ongoing advice and counseling.
    No preview · Article · Aug 2014 · Epilepsia
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    ABSTRACT: We evaluated the outcomes of intracranial electroencephalography (iEEG) recording and subsequent resective surgery in patients with magnetic resonance imaging (MRI) − negative temporal lobe epilepsy (TLE). Thirty-two patients were identified from the Mayo Clinic Epilepsy Surgery Database (Arizona, Florida, and Minnesota). Eight (25.0%) had chronic iEEG monitoring that recorded neocortical temporal seizure onsets; 12 (37.5%) had mesial temporal seizure onsets; 5 (15.6%) had independent neocortical and mesial temporal seizure onsets; and 7 (21.9%) had simultaneous neocortical and mesial seizure onsets. Neocortical temporal lobe seizure semiology was the only factor significantly associated with neocortical temporal seizure onsets on iEEG. Only 33.3% of patients who underwent lateral temporal neocorticectomy had an Engel class 1 outcome, whereas 76.5% of patients with iEEG-guided anterior temporal lobectomy that included the amygdala and the hippocampus had an Engel class 1 outcome. Limitations in cohort size precluded statistical analysis of neuropsychological test data.
    No preview · Article · Jul 2014 · Epilepsy research
  • Leeda Ahmadi · Elaine Wirrell
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    ABSTRACT: We present a case of a young boy with a large hemispheric dysplasia, generalized EEG abnormalities and intractable epilepsy who achieved seizure freedom and markedly improved cognitive outcome after functional hemispherectomy.
    No preview · Article · Jun 2014 · Seminars in Pediatric Neurology
  • Elaine Wirrell
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    ABSTRACT: An infant with infantile spasms is presented. Surgical treatment of spasms has increasingly become an option for the management of this difficult disease. This case reviews the issues related to, and the criteria necessary for the successful surgical management of infantile spasms.
    No preview · Article · Jun 2014 · Seminars in Pediatric Neurology

  • No preview · Article · Jun 2014 · Seminars in Pediatric Neurology

Publication Stats

4k Citations
523.24 Total Impact Points


  • 2008-2015
    • Mayo Clinic - Rochester
      • • Department of Laboratory Medicine & Pathology
      • • Division of Child and Adolescent Neurology
      Рочестер, Minnesota, United States
  • 2001-2015
    • The University of Calgary
      • • Department of Paediatrics
      • • Division of Neurology
      • • Section of Paediatric Neurology
      • • Department of Clinical Neurosciences
      Calgary, Alberta, Canada
  • 2014
    • University of Manitoba
      • Faculty of Medicine
      Winnipeg, Manitoba, Canada
    • Central Arkansas Veterans Healthcare System
      Washington, Washington, D.C., United States
  • 2013
    • University of California, Los Angeles
      Los Ángeles, California, United States
  • 2006
    • University of British Columbia - Vancouver
      • Department of Pediatrics
      Vancouver, British Columbia, Canada
  • 1999-2001
    • University of Saskatchewan
      • • Department of Pediatrics
      • • Division of Neurology
      Saskatoon, Saskatchewan, Canada
  • 1997-1998
    • Royal University Hospital
      Saskatoon, Saskatchewan, Canada
  • 1995-1996
    • Dalhousie University
      • Department of Pediatrics
      Halifax, Nova Scotia, Canada