Deep Brain Stimulation for Pediatric Dystonia.
Seminars in pediatric neurology
2021; 38: 100896
Role of child neurologists and neurodevelopmentalists in the diagnosis of cerebral palsy: A survey study.
Dystonia is one of the most common pediatric movement disorders and can have a profound impact on the lives of children and their caregivers. Response to pharmacologic treatment is often unsatisfactory. Deep brain stimulation (DBS) has emerged as a promising treatment option for children with medically refractory dystonia. In this review we highlight the relevant literature related to DBS for pediatric dystonia, with emphasis on the background, indications, prognostic factors, challenges, and future directions of pediatric DBS.
View details for DOI 10.1016/j.spen.2021.100896
View details for PubMedID 34183138
Lacosamide-Induced Dyskinesia in Children With Intractable Epilepsy.
Journal of child neurology
OBJECTIVE: To contextualize the role of child neurologists and neurodevelopmentalists (CN/NDDs) in cerebral palsy (CP) care, we review the changing landscape of CP diagnosis and survey stakeholder CN/NDDs regarding their roles in CP care.METHODS: The optimal roles of the multiple specialties involved in CP care are currently unclear, particularly regarding CP diagnosis. We developed recommendations regarding the role of CN/NDDs noting: (1) increasing complexity of CP diagnosis given a growing number of genetic etiologies and treatable motor disorders that can be misdiagnosed as CP, and (2) the views of a group of physician stakeholders (CN/NDDs from the Child Neurology Society Cerebral Palsy Special Interest Group).RESULTS: CN/NDDs felt that they were optimally suited to diagnose CP. Many (76%) felt CN/NDDs should always be involved in CP diagnosis. However, 42% said their CP patients were typically not diagnosed by CN/NDDs and 18% did not receive referrals to establish the diagnosis of CP at all. CN/NDDs identified areas of their expertise critical for CP diagnosis including knowledge of the neurologic exam across development and early identification of features atypical for CP. This contrasts with their views on CP management, where CN/NDDs felt they could contribute to the medical team, but were necessary primarily when neurologic co-existing conditions were present.DISCUSSION: Given its increasing complexity, we recommend early referral for CP diagnosis to a CN/NDD or specialist with comparable expertise. This contrasts with current consensus guidelines which either do not address or do not recommend specific specialist referral for CP diagnosis.
View details for DOI 10.1212/WNL.0000000000011036
View details for PubMedID 33046609
Clinical Approach to a Child with Movement Disorders
SEMINARS IN PEDIATRIC NEUROLOGY
2018; 25 (1): 10?18
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
Revealing the Prevalence and Consequences of Food Insecurity in Children with Epilepsy
JOURNAL OF COMMUNITY HEALTH
2017; 42 (6): 1213?19
Assessing movement can be especially challenging in children. Refined yet flexible observational examination skills and utilization of established phenomenological approaches are essential in distinguishing normal from abnormal movements in the developing child and reaching an appropriate diagnosis. Mastering such skill requires an appreciation of the unique features of the developing motor system and an understanding of key concepts underlying normal motor development in children. Establishing a trusting therapeutic relationship with the patient and family, minimizing anxiety, and utilizing observation and distraction during physical examination are essential to successful diagnosis and management.
View details for PubMedID 29735108
Interrogating the aged striatum: Robust survival of grafted dopamine neurons in aging rats produces inferior behavioral recovery and evidence of impaired integration
NEUROBIOLOGY OF DISEASE
2015; 77: 191?203
Food insecurity (FI) affects more than one in five American children and is increasingly addressed during pediatric primary care. Its relevance during subspecialty care, including in the treatment of chronic conditions like epilepsy, is largely unknown. This study sought to determine the FI prevalence among children with epilepsy and examine the relationship between FI and healthcare utilization, health-related quality-of-life (HR-QOL), and medication side effect control. This was a retrospective cohort study using electronic health record data from children, aged 2-17 years, seen for epilepsy management at an academic pediatric hospital. The primary predictor was household FI status, determined using a validated screening tool employed in the hospital's pediatric neurology clinics. The primary outcome was unplanned healthcare utilization in the 6 months following initial FI screen. Secondary outcomes were standardized, validated assessments of HR-QOL and epilepsy medication side effects. Nearly 14% of the 691 children seen in the clinics for epilepsy lived in food insecure households. The impact of FI on healthcare utilization varied by race. For Caucasians, healthcare utilization rates were significantly higher among food insecure individuals than food secure individuals (37 vs. 17%, p?=?0.003). Among African Americans, healthcare utilization rates did not vary with food security status (p?=?0.6). Children in food insecure households had lower HR-QOL (p?0.0001) and higher medication side effects (p?=?0.0005). FI is common among children with epilepsy and may influence adverse health outcomes. Further exploration into how FI and other social determinants influence management of and determine outcomes for chronic diseases is warranted.
View details for DOI 10.1007/s10900-017-0372-1
View details for Web of Science ID 000413972300018
View details for PubMedID 28477050
Advances in thin tissue Golgi-Cox impregnation: Fast, reliable methods for multi-assay analyses in rodent and non-human primate brain
JOURNAL OF NEUROSCIENCE METHODS
2013; 213 (2): 214?27
Advanced age is the primary risk factor for Parkinson's disease (PD). In PD patients and rodent models of PD, advanced age is associated with inferior symptomatic benefit following intrastriatal grafting of embryonic dopamine (DA) neurons, a pattern believed to result from decreased survival and reinnervation provided by grafted neurons in the aged host. To help understand the capacity of the aged, parkinsonian striatum to be remodeled with new DA terminals, we used a grafting model and examined whether increasing the number of grafted DA neurons in aged rats would translate to enhanced behavioral recovery. Young (3months), middle-aged (15months), and aged (22months) parkinsonian rats were grafted with proportionately increasing numbers of embryonic ventral mesencephalic (VM) cells to evaluate whether the limitations of the graft environment in subjects of advancing age can be offset by increased numbers of transplanted neurons. Despite robust survival of grafted neurons in aged rats, reinnervation of striatal neurons remained inferior and amelioration of levodopa-induced dyskinesias (LID) was delayed or absent. This study demonstrates that: 1) counter to previous evidence, under certain conditions the aged striatum can support robust survival of grafted DA neurons; and 2) unknown factors associated with the aged striatum result in inferior integration of graft and host, and continue to present obstacles to full therapeutic efficacy of DA cell-based therapy in this model of aging.
View details for DOI 10.1016/j.nbd.2015.03.005
View details for Web of Science ID 000353612200017
View details for PubMedID 25771169
View details for PubMedCentralID PMC4402284
Obese and Hungry in the Suburbs: The Hidden Faces of Food Insecurity
2012; 12 (3): 163?65
Impact of dendritic spine preservation in medium spiny neurons on dopamine graft efficacy and the expression of dyskinesias in parkinsonian rats
EUROPEAN JOURNAL OF NEUROSCIENCE
2010; 31 (3): 478?90
In 1873 Camillo Golgi discovered a staining technique that allowed for the visualization of whole neurons within the brain, initially termed 'the black reaction' and is now known as Golgi impregnation. Despite the capricious nature of this method, Golgi impregnation remains a widely used method for whole neuron visualization and analysis of dendritic arborization and spine quantification. We describe a series of reliable, modified 'Golgi-Cox' impregnation methods that complement some existing methods and have several advantages over traditional whole brain 'Golgi' impregnation. First, these methods utilize 60-100?m thick brain sections, which allows for fast, reliable impregnation of neurons in rats (7-14 days) and non-human primates (NHP) (30 days) while avoiding the pitfalls of other 'rapid Golgi' techniques traditionally employed with thin sections. Second, these methods employ several common tissue fixatives, resulting in high quality neuron impregnation in brain sections from acrolein, glutaraldehyde, and paraformaldehyde perfused rats, and in glutaraldehyde perfused NHP brain tissue. Third, because thin sections are obtained on a vibratome prior to processing, alternate sections of brain tissue can be used for additional analyses such as immunohistochemistry or electron microscopy. This later advantage allows for comparison of, for example, dendrite morphology in sections adjacent to pertinent histochemical markers or ultrastructural components. Finally, we describe a method for simultaneous light microscopic visualization of both tyrosine hydroxylase immunohistochemistry and Golgi impregnation in the same tissue section. Thus, the methods described here allow for fast, high quality Golgi impregnation and conserve experimental subjects by allowing multiple analyses within an individual animal.
View details for DOI 10.1016/j.jneumeth.2012.12.001
View details for Web of Science ID 000315557200007
View details for PubMedID 23313849
View details for PubMedCentralID PMC3574216
Neural repair strategies for Parkinson's disease: insights from primate models
2006; 15 (3): 251?65
Dopamine deficiency associated with Parkinson's disease (PD) results in numerous changes in striatal transmitter function and neuron morphology. Specifically, there is marked atrophy of dendrites and dendritic spines on striatal medium spiny neurons (MSN), primary targets of inputs from nigral dopamine and cortical glutamate neurons, in advanced PD and rodent models of severe dopamine depletion. Dendritic spine loss occurs via dysregulation of intraspine Cav1.3 L-type Ca(2+)channels and can be prevented, in animal models, by administration of the calcium channel antagonist, nimodipine. The impact of MSN dendritic spine loss in the parkinsonian striatum on dopamine neuron graft therapy remains unexamined. Using unilaterally parkinsonian Sprague-Dawley rats, we tested the hypothesis that MSN dendritic spine preservation through administration of nimodipine would result in improved therapeutic benefit and diminished graft-induced behavioral abnormalities in rats grafted with embryonic ventral midbrain cells. Analysis of rotational asymmetry and spontaneous forelimb use in the cylinder task found no significant effect of dendritic spine preservation in grafted rats. However, analyses of vibrissae-induced forelimb use, levodopa-induced dyskinesias and graft-induced dyskinesias showed significant improvement in rats with dopamine grafts associated with preserved striatal dendritic spine density. Nimodipine treatment in this model did not impact dopamine graft survival but allowed for increased graft reinnervation of striatum. Taken together, these results demonstrate that even with grafting suboptimal numbers of cells, maintaining normal spine density on target MSNs results in overall superior behavioral efficacy of dopamine grafts.
View details for DOI 10.1111/j.1460-9568.2010.07077.x
View details for Web of Science ID 000274165700008
View details for PubMedID 20105237
View details for PubMedCentralID PMC2940228
Nonhuman primate models of Parkinson's disease (PD) have been invaluable to our understanding of the human disease and in the advancement of novel therapies for its treatment. In this review, we attempt to give a brief overview of the animal models of PD currently used, with a more comprehensive focus on the advantages and disadvantages presented by their use in the nonhuman primate. In particular, discussion addresses the 6-hydroxydopamine (6-OHDA), 1-methyl-1,2,3,6-tetrahydopyridine (MPTP), rotenone, paraquat, and maneb parkinsonian models. Additionally, the role of primate PD models in the development of novel therapies, such as trophic factor delivery, grafting, and deep brain stimulation, are described. Finally, the contribution of primate PD models to our understanding of the etiology and pathology of human PD is discussed.
View details for DOI 10.3727/000000006783982025
View details for Web of Science ID 000237492500006
View details for PubMedID 16719060