Daune L MacGregor

SickKids, Toronto, Ontario, Canada

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Publications (69)213.73 Total impact

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    ABSTRACT: Alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism are two separate movement disorders with different dominant mutations in the same sodium-potassium transporter ATPase subunit gene, ATP1A3. We present a child with topiramate-responsive alternating hemiplegia of childhood who was tested for an ATP1A3 gene mutation. Gene sequencing revealed an identical ATP1A3 mutation as in three typical adult-onset rapid-onset dystonia parkinsonism cases but never previously described in an alternating hemiplegia of childhood case. The discordance of these phenotypes suggests that there are other undiscovered environmental, genetic, or epigenetic factors influencing the development of alternating hemiplegia of childhood or rapid-onset dystonia parkinsonism. Copyright © 2014 Elsevier Inc. All rights reserved.
    Pediatric neurology. 12/2014; 51(6):850-3.
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    ABSTRACT: Moyamoya disease is characterized by progressive cerebrovascular stenosis with recurrent cerebral ischemic events. Transient ischemic attacks are often associated with hyperventilation in children with moyamoya, suggesting hypoperfusion rather than thrombotic vaso-occlusion as a prominent mechanism. The patterns of ischemia and severity of steno-occlusive disease in such children may elucidate these mechanisms. Children, 1 month to 18 years, with moyamoya, observed over 11 years were analyzed. A study neuroradiologist reviewed all presurgical neuroimaging. Ischemic injury was categorized into cortical, subcortical, and watershed infarction. Angiographic findings were staged using a standardized method. Twenty children, 15 girls, median age 6.4 years, were included. All children had magnetic resonance imaging and angiography, and in 16, conventional angiography was available. All 40 hemispheres, in 20 children, were evaluated. The initial clinical presentation included neurological deficits in 17, recurrent transient ischemic attacks in 7, headache in 8, seizures in 8, and alteration in consciousness in 4 children. Infarcts were bilateral in 13 (65%) children (ischemia alone in 14, ischemic stroke with hemorrhagic transformation in two, and primary hemorrhage in two). Infarcts were cortical and/or subcortical in 13 (65%), both deep and cortical watershed in 11 (55%), and cortical watershed alone in 5 (25%) children. The predominant vascular territory involved was the middle cerebral artery. The internal carotid arterial system was involved in all, with stage IV being the most frequent angiographic stage. Ischemic injury in deep watershed zones is common in childhood moyamoya and may reflect non-vaso-occlusive ischemic mechanisms. Location and severity of vascular involvement may correlate with various patterns of ischemic infarction in moyamoya disease and requires further study. Copyright © 2014 Elsevier Inc. All rights reserved.
    Pediatric neurology. 10/2014;
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    ABSTRACT: To assess the safety and efficacy of antithrombotic therapy (ATT) for secondary stroke prevention of childhood bacterial meningitis.
    The Journal of pediatrics. 07/2014;
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    ABSTRACT: To describe the spectrum of central nervous system complications of varicella-zoster virus (VZV) in children admitted to The Hospital for Sick Children between January 1999 and December 2012.
    The Journal of pediatrics. 07/2014;
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    ABSTRACT: Primary human herpesvirus 7 (HHV-7) infection occurs almost universally during the first 5 years of life and is rarely accompanied by central nervous system (CNS) symptoms such as febrile seizures. The present retrospective study investigated the role of primary HHV-7 infection in CNS disease in children, including adolescents. The study included all children who had neurologic disease aged younger than 18 years seen at the Hospital for Sick Children, Toronto, Canada, between April 1, 1998 and December 31, 2011, whose cerebrospinal fluid (CSF) was found by polymerase chain reaction to contain HHV-7 DNA. Where sera were available, HHV-7 IgG antibody titers and avidity were measured to differentiate primary from past infection. HHV-7 DNA was detected in the CSF of 57 (1.9%) of the 2972 children tested. In 3 adolescents primary HHV-7 infection (low avidity IgG) was confirmed as the cause of neurologic disease, 2 who had encephalitis and 1 who had Guillain-Barré syndrome. Eighteen children had possible HHV-7 disease (no alternative cause identified and indeterminate antibody result or serum not available), 7 encephalitis, 8 meningitis, and 3 demyelinating disorders. HHV-7 disease was excluded in 36 children on the basis of past infection (high IgG avidity) and/or an alternative cause. Primary HHV-7 infection delayed into adolescence can cause serious neurologic disease. HHV-7 DNA in CSF alone is insufficient to prove an etiologic association. Combining CSF polymerase chain reaction with serology is essential to prove primary infection when investigating HHV-7 CNS disease.
    PEDIATRICS 05/2014; · 4.47 Impact Factor
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    ABSTRACT: This book provides recommendations for evaluation and therapy in the area of acute pediatric neurology; these are presented didactically with frequent use of illustrations and algorithms. Chapters in the first part of the book discuss presenting symptoms of acute neurological conditions. The second part of the book covers major areas of acute pediatric neurology and each of these chapters has three key elements: description of presenting symptoms; recommended assessments; and recommended interventions. Acute Pediatric Neurology provides an accessible, clinically focused guide to assist physicians in the emergency ward or intensive care unit in decisions on diagnosis and therapeutic interventions in all major acute pediatric neurological diseases.
    1st edited by Thomas Sejersen & Ching Wang, 01/2014; Springer., ISBN: 978-0-85729-490-6 (print), 978-0-85729-491-3 (Online)
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    ABSTRACT: Objectives. To describe our experiences in the management of the second wave of influenza A H1N1 (pH1N1) pandemic in a tertiary-care children's hospital. Methods. An autoethnographic study of the pandemic planning and management committee members involved in managing the second wave of pH1N1 was conducted. Results. Staffing, surge capacity, communications and emergency operations planning by adding leaders of frontline workers and other key operational roles to the incident management team, and creating a tactical response team emerged as important factors in pandemic management in our hospital. The emergency department visits increased by 50%, necessitating increased staffing of the emergency department. Communications using existing chains of command had to be used to reach frontline staff during the pandemic. Conclusions. Incident management teams managing pandemics and other disasters have to be dynamic and create tactical teams to ensure implementation and facilitate bidirectional communication with frontline workers.
    Clinical Pediatrics 02/2013; · 1.27 Impact Factor
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    ABSTRACT: AIM: To describe outcomes and outcome predictors in childhood basilar artery stroke (BAS). METHOD: We prospectively enrolled children with BAS with or without basilar artery occlusion (BAO) in the Toronto Children's Stroke Registry from 1992 to 2009. We assessed presenting features and outcomes including Pediatric Stroke Outcome Measure scores. RESULTS: Among 578 children with acute arterial ischemic stroke, 27 had BAS (4.6% including neonates, 6% excluding neonates). Twenty-four (14 males, 10 females) children met study criteria (mean age at stroke was 8y 10mo; range 0-17y). Eleven children had BAO. Aspirin or anticoagulation was given to 15 children. None received tissue plasminogen activator or endovascular treatments. At mean follow-up (3y 2mo, range 1mo-11y 8mo), 12 had a 'good outcome' (seven normal, five insignificant deficit) and 12 had 'poor outcome' (10 moderate or severe deficit, two acute deaths). Larger infarct size (≥50% of axial brainstem diameter) independently predicted poor outcome (p=0.02; odds ratio 21.2, 95% confidence interval 1.6-274.9) but not BAO, altered level of consciousness, or age. INTERPRETATION: Compared with adults, in childhood BAS death is rare and survivors frequently have good outcomes. Aggressive endovascular interventions may not be justifiable in this population.
    Developmental Medicine & Child Neurology 02/2013; · 2.68 Impact Factor
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    ABSTRACT: Aim  Wallerian degeneration is a radiological finding thought to reflect corticospinal tract degeneration. This finding on magnetic resonance imaging (MRI) is routinely used as a predictor of poor prognosis in childhood stroke. However, its validity has never been established. Our objective was to correlate Wallerian degeneration seen on MRI with histopathology. Method  We searched the databases of the Department of Pathology and Children's Stroke registry at the Hospital for Sick Children, Toronto for autopsy specimens exhibiting focal infarcts from children born at term who underwent MRI after a stroke. The specimens were examined for Wallerian degeneration and then correlated with the pre-mortem MRI findings. Results  Seven children (four females, three males) with a median age of 11 years (1-17y) at the time of stroke met the inclusion criteria for this study. Of the seven children included in the study with ischaemic or haemorrhagic infarcts, six had concordant Wallerian degeneration findings on both MRI and post-mortem histopathological examination. The median time between stroke and death was 20 days (3-1825d). Interpretation  Our results show for the first time that the radiographic finding of Wallerian degeneration is a valid biomarker of corticospinal tract degeneration in children who have had ischaemic or haemorrhagic stroke.
    Developmental Medicine & Child Neurology 11/2012; · 2.68 Impact Factor
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    ABSTRACT: Pediatric arterial ischemic stroke (AIS) carries an important morbidity and mortality burden. Congenital heart disease (CHD) is among the most important risk factors for pediatric AIS. Data on stroke recurrence in childhood CHD are lacking, resulting in uncertainty regarding optimal strategies for preventing recurrence. In the Canadian Pediatric Ischemic Stroke Registry-Toronto site, we identified children (birth to 18 years) with CHD diagnosed with AIS during 1992-2008. Data were abstracted from both stroke and cardiac surgery databases. Time-dependent outcomes (death and recurrent stroke) following sentinel stroke were parametrically modeled in competing risk analysis. Factors predicting stroke recurrence in parametric survival models were sought in parametric survival model analyses using backward variable selection of variables. A total of 135 patients (19 with recurrence, 116 without recurrence) were studied. In competing risk analysis, 10 years following sentinel stoke, 27% had experienced a stroke recurrence, 26% had died, and 47% were alive and free from recurrence. Stroke recurrence risk decreased over time from sentinel stroke. Approximately 50% of patients were receiving anticoagulation at recurrence. Significant factors associated with recurrence included the presence of a mechanical valve, prothrombotic condition, and an acute infection at the time of sentinel stroke. Hazard of mortality after recurrence was similar to mortality after sentinel stroke (hazard ratio, 1.3; p = 0.75). Stroke recurrence was relatively common in neonates and children with CHD. Identified groups of patients at increased risk may require more aggressive secondary prophylaxis, especially in the early poststroke period.
    Annals of Neurology 07/2012; 72(1):103-11. · 11.19 Impact Factor
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    ABSTRACT: The purpose of this study was to monitor developmental progress and identify predictors of developmental outcomes at 2 years after operation in infants who underwent a surgical procedure with cardiopulmonary bypass (CPB) at less than 3 months of age. Patients (N=131 enrolled; N=106 assessed) less than 3 months of age at the time of cardiac operation were prospectively enrolled (years 1999-2003) and assessed at 8, 12, and 24 months after operation. Patients with preexisting conditions independently associated with poor neurodevelopmental outcomes were excluded. Fine and gross motor development was formally assessed at all 3 visits, and parent ratings of development across several domains were obtained. Neurodevelopment was formally assessed at 24 months of age using the Bayley Scales of Infant Development, 2nd edition (BSID-II) Mental Development Index score (MDI). Significant gross motor difficulties were identified at 8 months of age (p<0.001) and, although improved by the 24-month assessment, remained lower than average. Fine motor skills showed a significant decrease from 8 to 24 months of age (p=0.001). Factors associated with poorer neurodevelopmental outcome (BSID-II MDI) at 24 months after operation included a diagnosis of univentricular anatomy or complex coarctation of the aorta, higher complexity of the surgical procedure, longer duration of hospital stay, and presence of complications in the postoperative period. Children undergoing repair of congenital heart disease (CHD) still have impaired development 2 years after the operation. Observed patterns of development were specific to the skill being assessed and related to both anatomic complexity and increased complexity of care received.
    The Annals of thoracic surgery 05/2012; 93(5):1577-83. · 3.45 Impact Factor
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    ABSTRACT: The Pediatric Stroke Outcome Measure (PSOM) is an objective, disease-specific outcome measure containing 115 test items suitable for newborn to adult ages. The PSOM measures neurological deficit and function across 5 subscales: right sensorimotor, left sensorimotor, language production, language comprehension, and cognitive/behavior yielding a final 10-point deficit score. The goal of this study was to examine PSOM construct validity in measuring neurological outcome in pediatric stroke survivors and interrater reliability (IRR) for both prospective and retrospective scoring. For construct validity, PSOM subscale scores were correlated with scores on standardized neuropsychological measures matched by functional domain. We assessed IRR by comparing same-day "live" PSOM scores from 2 independent raters in 10 children (prospective IRR) and by comparing PSOM scores estimated from medical dictations across 5 raters in another 10 children (retrospective IRR). We analyzed PSOM scores from 203 children with ischemic stroke. PSOM subscales show good construct validity (ρ=0.2-0.4; P<0.05). PSOM subscale scores of normal/abnormal demonstrate strong agreement for domain-matched neuropsychology scores (alternative chance-corrected statistic=0.4-0.8). IRR was excellent with the 2 prospective raters' scores in almost perfect agreement (intraclass correlation coefficient, 0.93; 95% CI, 0.76-0.98). Retrospective IRR demonstrated strong agreement with an intraclass correlation coefficient of 0.77 (95% CI, 0.56-0.92). The PSOM is a valid and reliable outcome measure for pediatric stroke. It is useful for retrospective scoring from health records and prospective serial longitudinal outcome assessments and is ideally suited for prospective clinical trials in pediatric stroke.
    Stroke 04/2012; 43(6):1602-8. · 6.16 Impact Factor
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    ABSTRACT: Pediatric arterial ischemic stroke (AIS) is increasingly diagnosed and carries significant risks of recurrence, morbidity, and mortality. Anticoagulant therapy (ACT) is commonly prescribed in childhood AIS. Hemorrhagic complication rates in pediatric stroke are unknown, and adult safety data are of limited applicability. We analyzed a prospectively enrolled cohort of children (aged 1 month-18 years) with acute AIS selected using standardized criteria for protocol-based ACT over 14-year period. We assessed ACT-associated intracranial hemorrhage (ICH), including frequency, clinical and radiologic characteristics, predictors, and outcome. Among 215 children with AIS, 123 received ACT within 7 days after diagnosis. During anticoagulation, 14 (11%) children developed new or increased ICH, all within 26 days from diagnosis. ICH was symptomatic in 5 (4%), asymptomatic in 9 (7%), and mild (European Cooperative Acute Stroke Study grades HI1 or HI2) in all but 1 child (ECASS PH-2). Long-term neurologic outcomes after ACT-associated ICH in survivors were abnormal in 73% (8/11). Comparably, 12 of 75 (16%) children treated without anticoagulation developed new or increased ICH on follow-up imaging (P = .3507). We conclude that ACT is relatively safe in children with AIS, with a 4% risk of symptomatic ICH. Based on the safety of ACT in our study, clinical trials of ACT in childhood AIS are warranted.
    Blood 12/2011; 119(4):949-56. · 9.78 Impact Factor
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    ABSTRACT:   Moyamoya vasculopathy is characterized by progressive stenosis of the major arteries of the Circle of Willis, resulting in compromised cerebral blood flow and increased risk of stroke. The objectives of the current study were to examine intellectual and executive functioning of children with moyamoya and to evaluate the impact of moyamoya type, stroke (clinical or silent), vasculopathy laterality, and disease duration on neurocognitive abilities.   Thirty pediatric participants (mean age 10 y 10 mo, SD 4 y; 18 females, 12 males) completed age-appropriate Wechsler Intelligence Scales before any therapeutic revascularization procedures. Reports of executive function were obtained from parents and teachers using the Behavior Rating Index of Executive Function.   Children with moyamoya scored significantly lower than the test standardization samples on all indices of intelligence and ratings of executive functioning (p<0.001). Patients did not differ by type of moyamoya or history of stroke. Patients with bilateral disease and stroke scored significantly lower than those with unilateral disease on measures of overall intellectual function (p=0.035) and verbal comprehension (p=0.04). Deficits in metacognitive executive functions were also more pronounced in bilateral patients according to teacher ratings.   Children with moyamoya are at risk for intellectual and executive problems, exacerbated by bilateral disease and clinical stroke history.
    Developmental Medicine & Child Neurology 11/2011; 54(1):30-7. · 2.68 Impact Factor
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    ABSTRACT: Holland Bloorview Kids Rehabilitation Hospital (formerly Bloorview Kids Rehab) is Canada's largest teaching hospital for pediatric rehabilitation and the only in-patient pediatric rehabilitation centre in Ontario. SickKids is a quaternary-level academic health sciences centre. The acute care neuroscience and trauma patient population at SickKids represents the largest volume of transitioning clients between the two organizations. For years, the number of medically unnecessary days associated with patients awaiting transfer from SickKids to Holland Bloorview for off-site rehabilitation was consistently driven by inefficient processes, multiple handovers, duplicitous efforts, fragmented communication and a lack of timely or complete referral information. Recognizing this situation as a threat to access, as well as a significant risk to patient health outcomes, SickKids and Holland Bloorview embarked on an exciting partnership (Kids in Transition: The Rehab Experience) as part of a larger Ministry of Health and Long-Term Care-funded initiative, the Flo Collaborative.
    Healthcare quarterly (Toronto, Ont.) 10/2011; 14 Spec No 3:77-82.
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    ABSTRACT: Predictors of quality of life can define potentially modifiable factors to increase favorable outcomes after pediatric stroke. Quality of life was measured using the Centre for Health Promotion's Quality of Life Profile (CHP-QOL) in 112 children surviving arterial ischemic stroke or cerebral sinovenous thrombosis at mean 3 years after stroke. Overall quality of life was poor in 17.8% children despite mean scores (3.52) in the "adequate" range. Quality of life related to school and play was most problematic and that related to physical and home environment was least problematic. Female gender, cerebral sinovenous thrombosis stroke, and older age at testing predicted reduced overall and domain-specific quality of life (P < .05), whereas neurological outcome and family socioeconomic status did not. Cognitive/behavioral deficit and low Verbal IQ adversely affected socialization and quality of life, especially among older children and females. Altered cognition/behavior has a major impact on quality of life after pediatric stroke. Implementation of ameliorative strategies warrants further study.
    Journal of child neurology 09/2011; 26(9):1186-92. · 1.59 Impact Factor
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    ABSTRACT: Neonatal cerebral sinovenous thrombosis is a frequent contributor to neonatal mortality and morbidity. Treatment is controversial, and reported clinical outcomes vary widely. Newborns with radiologically confirmed neonatal cerebral sinovenous thrombosis from 1992 to 2009 were prospectively followed in our Children's Stroke Clinic for standardized outcomes, including the Pediatric Stroke Outcome Measure. Outcomes were available in 90 of 104 (87%) neonates. Early outcomes included cerebral sinovenous thrombosis-associated death (5) and thrombus propagation (15 [6 associated with new venous infarcts]). Lack of anticoagulation predicted propagation (RR = 13; P = .0007). Complete thrombus recanalization occurred in 90% by 3 months. Late outcomes (median, 2.5 years) were epilepsy (15) and neurological disability (50), which included moderate-severe language (43), sensorimotor (38), and cognitive/behavioral (24) deficits. Overall, 61% had poor outcome (death/any deficit). Concurrent neurological comorbidity at diagnosis (odds ratio = 2.8; P = .029) predicted poor outcome. Clinical trials are urgently needed to establish more effective treatment strategies.
    Journal of child neurology 05/2011; 26(9):1137-44. · 1.59 Impact Factor
  • European Journal of Paediatric Neurology 05/2011; 15. · 1.98 Impact Factor
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    ABSTRACT: Neonatal stroke is increasingly recognized, and risk factors have been identified. The placenta has been implicated as a potential contributor to neonatal stroke; however, pathology has not been previously described. This case series systematically evaluates prenatal, maternal, and neonatal risk factors and describes placental pathology in 12 cases of neonatal stroke. We reviewed the Canadian Pediatric Ischemic Stroke Registry from 1992 to 2006, which consists of 186 neonatal stroke patients. Twelve patients with symptomatic cerebral arterial ischemic stroke or sinovenous thrombosis had their placenta available for pathologic examination. Clinical presentation; maternal, prenatal, and neonatal risk factors for stroke; and patient outcome were collected retrospectively from patient charts. Gross and microscopic placental pathology was described and classified into 4 pathologic categories. Of 12 patients studied, 10 patients were male, 5 patients had arterial ischemic stroke, and 7 patients had sinovenous thrombosis. Maternal risk factors were identified in 5 cases, prenatal risk factors in 10 cases, and neonatal risk factors in 10 cases. Placental lesions were present in 10 cases and were classified as thromboinflammatory process in 6 cases, sudden catastrophic event in 5 cases, decreased placental reserve in 3 cases, and stressful intrauterine environment in 2 cases. This study reviews detailed placental pathology in a selected cohort of patients presenting near the time of delivery and correlates this with clinical presentation, outcome, and risk factors for neonatal stroke. Our results suggest that multiple risk factors are involved in neonatal stroke, and placental pathology may be a contributing factor. The implications of specific placental lesions remain to be determined with larger, case-controlled studies.
    PEDIATRICS 02/2011; 127(3):e722-9. · 4.47 Impact Factor
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    ABSTRACT: Peer assessment has become an important component of physician evaluation. In an academic health sciences centre, in addition to clinical care there is a significant focus on education, training and research. The literature suggests that the use of a 360-degree evaluation can provide physicians with valuable information on many aspects of their practice and can inform both professional and personal development. We conducted a pilot study to determine the feasibility of using peer assessment as part of the evaluation of our academic physicians. To maintain anonymity, an outside company was engaged to conduct the study. Participants completed a self-assessment and provided the names of eight physician peers and eight non-physician peers who were then requested to complete an evaluation. In addition, 25 patients were asked to provide their feedback. All questionnaires were forwarded directly to the outside company, which then compiled the data and provided each participant with a final report. Results indicate that it is feasible to carry out peer assessment within an academic health sciences centre. Participants noted the value of the process for career development and quality improvement.
    Healthcare quarterly (Toronto, Ont.) 01/2011; 14(1):50-5.

Publication Stats

1k Citations
213.73 Total Impact Points

Institutions

  • 2001–2014
    • SickKids
      • • Division of Neurology
      • • Department of Paediatrics
      Toronto, Ontario, Canada
  • 1998–2012
    • University of Toronto
      • • Division of Neurology
      • • Hospital for Sick Children
      Toronto, Ontario, Canada
  • 2004
    • Riley Hospital for Children
      Indianapolis, Indiana, United States