Wendy G. Mitchell

Children's Hospital Los Angeles, Los Ángeles, California, United States

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Publications (81)296.77 Total impact

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    ABSTRACT: Background: Limited empirical investigation exists into longitudinal changes in cognition, behavior or quality of life (QOL) in children with perinatal HIV who are prescribed stimulants. Methods: This study was an analysis of longitudinal data from children age 3-19 years, with perinatal HIV infection, with and without prescriptions for stimulant medications [prescription (PG) and comparison (CG) groups, respectively], matched on age, availability of CD4% and outcome measures of cognition, behavior and QOL. Generalized estimating equation models were used to evaluate effects of stimulant exposure on change in measured outcomes over 3 years of follow-up, adjusting for baseline levels of outcomes and relevant covariates. Results: Children in both the PG (n = 132) and the CG (n = 392) obtained mean verbal and performance (nonverbal) intelligence quotients (VIQ and PIQ, respectively) in the low-average range for age. At baseline, those in PG demonstrated more frequent signs of hyperactivity, impulsivity and conduct and learning problems than those in CG (P ≤ 0.003 in unadjusted analyses). At follow-up, after adjustment for baseline functioning and other relevant covariates, there were no significant changes from baseline in VIQ or PIQ. Stimulant prescription use, however, was associated with worsening symptoms of hyperactivity (P = 0.01), impulsivity (P = 0.04), learning problems (P < 0.001) and worsening of perceived health status (P < 0.001). Conclusions: The results suggest expectations for behavioral improvement may not align well with long-term effects of stimulant prescription use on behavior and QOL in children with HIV. Further research is necessary to determine if there are subsets of children who may benefit from stimulant therapy.
    No preview · Article · Oct 2015 · The Pediatric Infectious Disease Journal
  • Jay Desai · Leigh Ramos-Platt · Wendy G Mitchell
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    ABSTRACT: Pediatric chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon acquired disorder of unknown cause, presumed to have an immunological basis. We report 20 patients seen at Children's Hospital Los Angeles over a period of 10 years. The outcome of our patients was favorable in a vast majority with good response to various treatments instituted. However, residual neurologic deficit was common. The choice of treatment modality was empirical and selected by the treating neurologist. Intravenous immunoglobulin (IVIG) and corticosteroids were most commonly utilized for treatment. Plasmapheresis, mycophenolate mofetil, rituximab, cyclophosphamide, azathioprine, and abatacept were added if the patients were refractory to IVIG or became corticosteroid dependent. The spectrum of disease severity ranged from a single monophasic episode, to multiphasic with infrequent relapses with good response to IVIG, to progressive disease refractory to multiple therapies.
    No preview · Article · Oct 2015 · Annals of Indian Academy of Neurology
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    ABSTRACT: The peak age at onset of Lennox-Gastaut syndrome (LGS) is between 3 and 5years. Patients with LGS frequently experience multiple types of treatment-refractory seizures and require lifelong therapy with several antiepileptic drugs. Here, post hoc analyses of clinical trials (phase III trial OV-1012 and open-label extension trial OV-1004) provide short- and long-term efficacy and safety data of adjunctive clobazam in patients with LGS stratified by age at baseline (≥2 to <12years, ≥12 to <17years, and ≥17years). In OV-1012, 301 patients were screened, 238 were randomized, 217 comprised the modified intention-to-treat population, and 177 completed the study. A total of 267/306 patients (61 of 68 from phase II trial OV-1002 and 206 of 238 from phase III trial OV-1012) entered the open-label extension trial. Demographics and clinical characteristics were similar between different age groups in OV-1012 and OV-1004. No differences in efficacy or adverse events were observed across age groups in OV-1012 and OV-1004. The results of these post hoc analyses show that adjunctive clobazam over the short and longterm was similarly effective and well-tolerated in both pediatric and adult patients with LGS. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · May 2015 · Epilepsy & Behavior
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    ABSTRACT: Objective To determine long-term safety and efficacy of adjunctive clobazam for patients with Lennox-Gastaut syndrome (LGS). Methods Eligible patients from two randomized controlled trials (Phase II OV-1002 and Phase III OV-1012) were able to enroll in open-label extension (OLE) study OV-1004 beginning in December 2005 and received clobazam until they discontinued (mandatory at 2 years for patients outside the United States) or until study completion in March 2012. Patients in the United States could have received clobazam for 6 years before it became commercially available. Efficacy assessments included changes in rates of drop seizures and total seizures, responder rates (≥50%, ≥75%, or 100% decreases in seizure frequency vs. baseline), sustained efficacy over time, concomitant antiepileptic drug (AED) use, and global evaluations. Safety assessments included exposure to clobazam, laboratory assessments, physical and neurologic examinations, vital sign monitoring, electrocardiography monitoring, and adverse event reporting. ResultsOf 267 patients who enrolled in the OLE, 188 (70%) completed the trial. Two hundred seven patients were from the United States, which was the only country in which patients could be treated with clobazam for >2 years. Forty-four patients were treated with clobazam for 5 years, and 11 for 6 years. Because of the low number of Year 6 patients, this group is not reported separately. Improvements in baseline seizure rates were very stable over the course of the study, with a median 85% decrease in drop seizures at Year 1, 87% at Year 2, 92% at Year 3, 97% at Year 4, and a 91% decrease for patients who had reached Year 5. Similar results were observed for total seizures (79% decrease at both Years 1 and 2, 82% decrease at Year 3, 75% decrease at Year 4, and 85% decrease at Year 5). Responder rates were also stable for the duration of the trial. Of patients who had achieved a ≥50% decrease in median drop-seizure frequency from baseline to Month 3, 86% still had that degree of drop-seizure reduction at Year 3 (and 14% lost their initial responses), and 47% were drop-seizure–free. Most patients who had achieved drop-seizure freedom in the original controlled trials remained drop-seizure–free in the OLE. Based on parents' and physicians' ratings of global evaluations, 80% of patients were “very much improved” or “much improved” after 3 years. Of the 43 patients with concomitant AED data who were treated for 5 years, 30% increased, 19% decreased, and 51% had no change in numbers of AEDs versus their Week 4 regimens. The mean modal clobazam dosage was 0.90 mg/kg/day at Year 1 and 0.97 mg/kg/day at Year 5, suggesting that study patients did not need significant increases in dosage over time. The safety profile was what would be expected for clobazam for LGS patients over a 5-year span, and no new safety concerns developed over time. SignificanceIn this largest and longest-running trial in LGS, adjunctive clobazam sustained seizure freedom and substantial seizure improvements at stable dosages through 3 years of therapy in this difficult- to-treat patient population.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
    Full-text · Article · Feb 2014 · Epilepsia
  • Jay Desai · Wendy G Mitchell
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    ABSTRACT: We report relevant results of a survey that was aimed at understanding current practice variations in the assessment of control of typical childhood absence epilepsy.
    No preview · Article · Mar 2013 · Journal of child neurology
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    ABSTRACT: In an ongoing open-label extension (OV-1004), patients with Lennox-Gastaut syndrome who had completed 1 of 2 randomized controlled trials (OV-1002 [Phase II] or OV-1012 [Phase III]) are receiving clobazam at dosages ≤2.0mg/kg/day (≤80mg/day). Of 306 eligible patients from OV-1002 or OV-1012, 267 entered the open-label extension. As of the interim date, July 1, 2010, 213 patients (79.8%) had remained in the trial, and 189 had received clobazam for ≥12months, 128 for ≥18months, and 94 for ≥24months. Median percentage decreases in average weekly rates of drop seizures were 71.1% and 91.6% at Months 3 and 24. Mean modal and mean maximum daily dosages were 0.94mg/kg and 1.22mg/kg for those who had received clobazam for ≥1year. The 4 most common adverse events were upper respiratory tract infection (18.4%), fall (14.2%), pneumonia (13.9%), and somnolence (12.7%). Clobazam's adverse event profile was consistent with its profile in controlled trials.
    Full-text · Article · Nov 2012 · Epilepsy & Behavior
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    Jay Desai · Wendy G Mitchell
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    ABSTRACT: Acute cerebellar ataxia and acute cerebellitis represent a process characterized by parainfectious, postinfectious, or postvaccination cerebellar inflammation. There is considerable overlap between these entities. The mildest cases of acute cerebellar ataxia represent a benign condition that is characterized by acute truncal and gait ataxia, variably with appendicular ataxia, nystagmus, dysarthria, and hypotonia. It occurs mostly in young children, presents abruptly, and recovers over weeks. Neuroimaging is normal. Severe cases of cerebellitis represent the other end of the spectrum, presenting with acute cerebellar signs often overshadowed by alteration of consciousness, focal neurological deficits, raised intracranial pressure, hydrocephalus, and even herniation. Neuroimaging is abnormal and the prognosis is less favorable than in acute cerebellar ataxia. Acute disseminated encephalomyelitis may be confused with acute cerebellitis when the clinical findings are predominantly cerebellar, but lesions on neuroimaging are usually widespread. Paraneoplastic opsoclonus-myoclonus syndrome is often initially misdiagnosed as acute cerebellar ataxia, but has very specific features, course, and etiopathogensis.
    Preview · Article · Jul 2012 · Journal of child neurology
  • W. Mitchell · J. Conry · Y.-t. Ng · R. Drummond · R. Owen

    No preview · Article · Apr 2012 · Neurology
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    ABSTRACT: To test the efficacy and safety of corticotropin-based immunotherapies in pediatric opsoclonus-myoclonus syndrome, 74 children received corticotropin alone or with intravenous immunoglobulin (groups 1 and 2, active controls); or both with rituximab (group 3) or cyclophosphamide (group 4); or with rituximab plus chemotherapy (group 5) or steroid sparers (group 6). There was 65% improvement in motor severity score across groups (P < .0001), but treatment combinations were more effective than corticotropin alone (P = .0009). Groups 3, 4, and 5 responded better than group 1; groups 3 and 5 responded better than group 2. The response frequency to corticotropin was higher than to prior corticosteroids (P < .0001). Fifty-five percent had adverse events (corticosteroid excess), more so with multiagents (P = .03); and 10% had serious adverse events. This study demonstrates greater efficacy of corticotropin-based multimodal therapy compared with conventional therapy, greater response to corticotropin than corticosteroid-based therapy, and overall tolerability.
    No preview · Article · Feb 2012 · Journal of child neurology
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    ABSTRACT: Association of occipital intermittent rhythmic delta activity with absence seizures has been well documented in the published literature. Two recent studies have also described an association with focal seizures. After obtaining approval from our Institutional Review Board, all electroencephalograms with occipital intermittent rhythmic delta activity at our institution between July 1, 2006 and December 31, 2009 were identified. Charts of these patients were reviewed to collect clinical data. A matched comparison group was assembled. Thirty-one of the patients who met criteria had evaluable clinical data. Fifteen had generalized seizures (9 absence; 2 tonic-clonic; 3 absence and tonic-clonic; 1 absence, tonic-clonic, myoclonic, and atonic). Eleven had focal seizures. One had both generalized tonic-clonic and focal seizures. Events in 1 were nonepileptic in nature. Documentation was inadequate for seizure classification in 3. There was a statistically significant difference between the study and comparison groups for absence seizures, but not for focal seizures.
    Full-text · Article · Sep 2011 · Journal of child neurology
  • Jay D Desai · Maria T Toczek · Wendy G Mitchell
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    ABSTRACT: Frontal intermittent rhythmic delta activity (FIRDA) has been studied extensively in adults but published literature about its clinical correlates in children and adolescents is comparatively limited. This study was performed to find more evidence regarding the clinical significance of this electrographic pattern in the pediatric population. All electroencephalograms (EEGs) with FIRDA between 07/01/2006 and 12/31/2009 at our institution were identified. Clinical data were collected from charts of patients with FIRDA. A comparison group consisting of patients matched for age and location was assembled. We identified 26 EEGs in 22 patients with this electrographic pattern from a total of 4627 EEGs. All 26 EEGs were performed because of a history of seizures or to rule out seizures. Two of the 22 patients did not have evaluable clinical data. Of the remaining, 18 had seizures. The events in 2 patients were determined to be non epileptic. Amongst the 18 patients with seizures, 10 had associated epileptiform discharges and only 2 were without epileptiform activity or localizing or lateralizing features. Two patients had brain tumor. Six patients had hydrocephalus. Three patients had encephalopathy due to anoxic, metabolic or infectious etiology. There was no statistically significant difference between the study and the comparison group for occurrence of brain tumor, hydrocephalus or encephalopathy. FIRDA was uncommonly observed. It was associated with a variety of conditions and was not a specific marker of brain tumor, hydrocephalus or encephalopathy.
    No preview · Article · Jul 2011 · European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society
  • Jay Desai · Wendy G Mitchell
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    ABSTRACT: Objectives: To study adding an anticonvulsant in children with uncontrolled epilepsy on ≥ 1 appropriate anticonvulsants. Methods: Chart review, patients with intractable epilepsy in a neurology clinic July 1, 2004 to December 31, 2007. Inclusion: Children on ≥ 1 stable anticonvulsant who had a second, third, or fourth anticonvulsant added. Exclusions: Noncompliance, subtherapeutic doses, and/or serum anticonvulsant levels, inappropriate anticonvulsant for seizure type, inadequate documentation, infantile spasms, or significant dosage changes in the baseline anticonvulsant(s) over the follow-up period. Patients were followed until further therapeutic changes occurred or September 30, 2008, whichever came first. Outcome: ≥ 50% decrease in seizure frequency. Results: Charts reviewed: 1886. Patients who met criteria: 84. Time to assessment: 4 weeks to 42 months (median = 7 months). ≥ 50% reduction in seizure frequency: 35 of 52 patients with second agent added; 5 of 30 patients with third agent added (P = .0001). Conclusions: Worthwhile seizure reduction is reasonably likely with the addition of a second anticonvulsant, but much less likely with the addition of third anticonvulsant.
    No preview · Article · Dec 2010 · Journal of child neurology
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    ABSTRACT: Mitochondrial dysfunction has been associated with both human immunodeficiency virus (HIV) infection and exposure to antiretroviral therapy. Mitochondrial dysfunction has not been widely studied in HIV-infected children. We estimated the incidence of clinically defined mitochondrial dysfunction among children with perinatal HIV infection. Children with perinatal HIV infection enrolled in a prospective cohort study (Pediatric AIDS Clinical Trials Group protocols 219 and 219C) from 1993 through 2004 were included. Two clinical case definitions of mitochondrial dysfunction, the Enquête Périnatale Française criteria and the Mitochondrial Disease Classification criteria, were used to classify signs and symptoms that were consistent with possible mitochondrial dysfunction. Adjusted odds ratios of the associations between single and dual nucleoside reverse-transcriptase inhibitor use and possible mitochondrial dysfunction were estimated using logistic regression. Overall, 982 (33.5%) of 2931 children met 1 or both case definitions of possible mitochondrial dysfunction. Mortality was highest among the 96 children who met both case definitions (20%). After adjusting for confounders, there was a higher risk of possible mitochondrial dysfunction among children who received stavudine regardless of exposure to other medications (odds ratio, 3.44 [95% confidence interval, 1.91-6.20]) or who received stavudine-didanosine combination therapy (odds ratio, 2.23 [95% confidence interval, 1.19-4.21]). Exposure to lamivudine and to lamivudine-stavudine were also associated with an increased risk of mitochondrial dysfunction. Receipt of nucleoside reverse-transcriptase inhibitors, especially stavudine and lamivudine, was associated with possible mitochondrial dysfunction in children with perinatal HIV infection. Further studies are warranted to elucidate potential mechanisms of nucleoside reverse-transcriptase inhibitor toxicities.
    Full-text · Article · Jul 2010 · The Journal of Infectious Diseases
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    ABSTRACT: To examine the relationships between physical growth and medications prescribed for symptoms of attention-deficit hyperactivity disorder in children with HIV. Analysis of data from children with perinatally acquired HIV (N = 2251; age 3-19 years), with and without prescriptions for stimulant and nonstimulant medications used to treat attention-deficit hyperactivity disorder, in a long-term observational study. Height and weight measurements were transformed to z scores and compared across medication groups. Changes in z scores during a 2-year interval were compared using multiple linear regression models adjusting for selected covariates. Participants with (n = 215) and without (n = 2036) prescriptions were shorter than expected based on US age and gender norms (p < .001). Children without prescriptions weighed less at baseline than children in the general population (p < .001) but gained height and weight at a faster rate (p < .001). Children prescribed stimulants were similar to population norms in baseline weight; their height and weight growth velocities were comparable with the general population and children without prescriptions (for weight, p = .511 and .100, respectively). Children prescribed nonstimulants had the lowest baseline height but were similar to population norms in baseline weight. Their height and weight growth velocities were comparable with the general population but significantly slower than children without prescriptions (p = .01 and .02, respectively). The use of stimulants to treat symptoms of attention-deficit hyperactivity disorder does not significantly exacerbate the potential for growth delay in children with HIV and may afford opportunities for interventions that promote physical growth. Prospective studies are needed to confirm these findings.
    Full-text · Article · Oct 2009 · Journal of developmental and behavioral pediatrics: JDBP
  • Arthur Partikian · Wendy G Mitchell
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    ABSTRACT: Studies have suggested disparate variables affecting long-term outcomes in patients with infantile spasms. Using a retrospective chart review, the authors identified 109 patients who had follow-up data for at least 1 year since the onset of spasms. Patient and treatment variables were recorded, in addition to neurodevelopmental and seizure outcomes. Etiology was strongly associated with motor and cognitive status but not with long-term seizure control. Lag time to initiation of treatment was not predictive of any outcome, nor for need to use a second agent to resolve spasms, even when controlling for etiology. However, patients who responded to the first medication achieved superior seizure and cognitive outcomes. The delayed impact of individual medications could not be analyzed because many patients received multiple agents. While etiology and response to first medication predict better outcomes, the majority of patients with infantile spasms continue to have epilepsy with long-term motor and cognitive disabilities.
    No preview · Article · Sep 2009 · Journal of child neurology
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    ABSTRACT: The aim of this study is to describe the long-term neurological, neuropsychological and neuroradiological sequelae and to determine prognostic factors for neurological outcome in children with neuroblastoma-associated opsoclonus-myoclonus-ataxia (OMA) syndrome. Data on medical history were collected for the study patients. Examinations with grading of neurological signs, neuropsychological tests and brain magnetic resonance imaging with spectroscopy were performed during a follow-up clinic. Fourteen subjects entered the study. All had localized neuroblastoma and they were evaluated after a median of 7.8 years. Patients with a chronic/multiphasic neurological course received steroids combined with intravenous immunoglobulins in the majority of cases. 71% presented neurological sequelae and 62% had a full-scale IQ below the normal range. All patients showed at least some deficit in the neuropsychological functions assessed (language, visual-motor integration, memory, attention and motor ability). Long-term deficits were more frequently detected in patients with an interval of more than 2 months between OMA onset and its diagnosis, even if in most comparisons statistical significance was not reached. Cerebellar atrophy, observed in 36% of patients, was not associated with the neurological outcome. Persisting disability is present in most children with neuroblastoma-associated OMA. However, our results support the role of an early diagnosis of OMA in reducing sequelae and encourage the use of new immunosuppressive therapies.
    No preview · Article · Aug 2009 · Neuropediatrics
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    ABSTRACT: We report a case of a 5-year-old boy with intractable epilepsy who underwent therapeutic corticectomy. Histopathologic findings within the resection specimen included severe cortical dysplasia associated with abundant subpial and intraparenchymal Rosenthal fibers in a large right frontal lesion that merged into the basal ganglia. Rosenthal fiber proliferation may represent a reactive process, are frequent in pilocytic astrocytomas, and are a defining feature of Alexander disease. There was no evidence of neoplasm or leukodystrophy in this case. Genetic analysis of the specimen showed a few previously reported polymorphisms but no mutation in the GFAP gene. This case is unique among several hundred cortical resection specimens that we have studied, including numerous cases of severe cortical dysplasia.
    No preview · Article · Jun 2009 · Human pathology
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    ABSTRACT: Opsoclonus-myoclonus syndrome is characterized by abnormal lymphocyte trafficking into brain. The authors hypothesized that mycophenolate mofetil, a lymphocyte proliferation inhibitor, might be therapeutic. The cerebrospinal fluid and blood immunophenotypes of 15 children with predominantly chronic-relapsing opsoclonus-myoclonus syndrome were compared before and after treatment by flow cytometry. Mycophenolate mofetil reduced the cerebrospinal fluid expansion of HLA-DR+ activated T cells (-40%); the frequency of other T-cell or natural killer cell subsets remained unchanged, but cerebrospinal fluid B cells increased significantly. Adrenocorticotropic hormone dose was lowered by 64% over an average of 1.5 years, yet 73% eventually relapsed despite therapeutic drug levels. Prior treatment with rituximab prevented relapse-associated increase in cerebrospinal fluid B cells, without hindering mycophenolate mofetil-induced reduction in T-cell activation. These data demonstrate resistant immunologic problems in chronic-relapsing opsoclonus-myoclonus syndrome. Mycophenolate mofetil did not prevent relapse. The novel effect of mycophenolate mofetil on chronically activated T cells may contribute to its efficacy in T-cell mediated neurological disorders.
    Full-text · Article · Apr 2009 · Journal of child neurology
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    ABSTRACT: This randomized, double-blind, dose-ranging study evaluated safety and efficacy of clobazam (CLB) as adjunctive therapy for drop seizures in patients with Lennox-Gastaut syndrome (LGS). Sixty-eight patients with LGS aged 2-26 years were administered CLB (low dose = target 0.25 mg/kg/day; high dose = target 1.0 mg/kg/day). The study consisted of 4-week baseline, 3-week titration, and 4-week maintenance periods, followed by a 3-week taper or continuation in an open-label study. Seizure frequency was recorded in a diary by the parent/caregiver throughout the study. Weekly drop seizure rates were significantly reduced from baseline in both the high-dose and low-dose groups; the reduction was significantly greater in the high-dose group. A significantly greater proportion of patients in the high-dose group experienced reductions in drop seizures of >or=25%, >or=50%, and >or=75% compared to the low-dose group; more patients in the high-dose group experienced a 100% reduction, but the difference was not significant. Nondrop seizures were also reduced in a dose-dependent manner. In both investigator and parent/caregiver global evaluations, patients in the high-dose group showed significantly greater improvements in overall symptoms compared to low-dose CLB. Adverse events were generally mild or moderate, and were similar between dose groups. Five serious adverse events were reported in four patients, but in no case was CLB discontinued. Clobazam was well tolerated and reduced drop seizure rates; high-dose CLB was more effective than low-dose CLB. Other seizure types were also reduced.
    Full-text · Article · Dec 2008 · Epilepsia
  • Wendy G Mitchell · Linda Tseng-Ong

    No preview · Article · Aug 2008 · Journal of child neurology

Publication Stats

2k Citations
296.77 Total Impact Points


  • 1985-2015
    • Children's Hospital Los Angeles
      • • DIvision of Neurology
      • • Department of Pediatrics
      Los Ángeles, California, United States
  • 1996-2013
    • University of California, Los Angeles
      • Department of Neurology
      Los Ángeles, California, United States
  • 2009
    • St. Jude Children's Research Hospital
      Memphis, Tennessee, United States
  • 1999-2006
    • Wolfson Childrens Hospital
      Jacksonville, Florida, United States
    • Oregon State University
      • Department of Statistics
      Corvallis, OR, United States
  • 1991-2006
    • University of Southern California
      • • Keck School of Medicine
      • • Department of Neurology
      Los Ángeles, California, United States
  • 2002
    • California State University, Northridge
      Northridge, Ohio, United States
  • 1994-2001
    • Weill Cornell Medical College
      • Department of Public Health
      New York, New York, United States
  • 1990
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 1983
    • University of North Carolina at Chapel Hill
      • Department of Radiology
      North Carolina, United States