Pediatric Neurology Workforce in Canada: A 5-Year Update.

BACKGROUND: In 2013, a task force was developed to discuss the future of the Canadian pediatric neurology workforce. The consensus was that there was no indication to reduce the number of training positions, but that the issue required continued surveillance. The current study provides a 5-year update on Canadian pediatric neurology workforce data. METHODS: Names, practice types, number of weekly outpatient clinics, and dates of certification of all physicians currently practicing pediatric neurology in Canada were obtained. International data were used to compute comparisons between countries. National data sets were used to provide information about the number of residency positions available and the number of Canadian graduates per year. Models for future projections were developed based on published projected population data and trends from the past decade. RESULTS: The number of pediatric neurologists practicing in Canada has increased 165% since 1994. During this period, wait times have not significantly shortened. There are regional discrepancies in access to child neurologists. The Canadian pediatric neurology workforce available to see outpatient consultations is proportionally less than that of USA. After accounting for retirements and emigrations, the number of child neurologists being added to the workforce each year is 4.9. This will result in an expected 10-year increase in Canadian pediatric neurologists from 151 to 200. CONCLUSIONS: Despite an increase in the number of Canadian child neurologists over the last two decades, we do not predict that there will be problems with underemployment over the next decade.

Les effectifs en neurologie pédiatrique au Canada : une mise à jour tenant compte des cinq dernières années.Contexte:En 2013, un comité de réflexion a été mis sur pied afin de discuter de l'avenir des effectifs canadiens en neurologie pédiatrique. Un consensus s'est alors dessiné : bien que rien n'indique qu'il faille réduire le nombre de places disponibles dans ce domaine de formation, cette question nécessite toutefois un suivi continu. La présente étude vise ainsi à offrir une mise à jour des données qui concernent ces effectifs en tenant compte des cinq dernières années.Méthodes:Les données suivantes ont été obtenues : noms des praticiens, types de pratique, nombre de consultations hebdomadaires en clinique externe et dates de certification de tous les médecins pratiquant actuellement la neurologie pédiatrique au Canada. Des données internationales ont également été utilisées pour effectuer des comparaisons entre divers pays. Des données au niveau national ont été rassemblées pour établir le nombre de places disponibles en résidence et le nombre de diplômés canadiens par année. Des modèles de projection ont aussi été élaborés en se fondant sur des projections de population déjà publiées et sur les tendances ayant marqué la décennie précédente.Résultats:Le nombre de neurologues pédiatriques qui pratiquent au Canada a augmenté de 165 % depuis 1994. Fait à noter, les temps d'attente n'ont pas été notablement raccourcis durant cette période. Il existe aussi des disparités régionales en matière d'accès à cette spécialité de la neurologie. Les effectifs canadiens en neurologie pédiatrique disponibles pour des consultations en clinique externe demeurent proportionnellement moins importants qu'aux États-Unis. Après avoir tenu compte des départs à la retraite et des apports de l'extérieur, le nombre de neurologues pédiatriques ajoutés chaque année a été en moyenne de 4,9. Pendant une période de 10 ans, on anticipe donc qu'on devrait passer de 151 à 200 neurologues pédiatriques canadiens.Conclusions:En dépit d'une hausse du nombre de neurologues pédiatriques canadiens au cours des deux dernières décennies, nous ne prédisons pas de problèmes de sous-emploi au cours de la prochaine décennie.

BAFopathies' DNA methylation epi-signatures demonstrate diagnostic utility and functional continuum of Coffin-Siris and Nicolaides-Baraitser syndromes.

Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboring ARID1B deletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening.

Lethal Neonatal Rigidity and Multifocal Seizure Syndrome--A Misnamed Disorder?

OBJECTIVE: Lethal neonatal rigidity and multifocal seizure syndrome is a newly recognized genetic disorder associated with early onset of rigidity, multifocal epilepsy, developmental arrest, and early death. It is an autosomal recessive condition resulting from a mutation in the BRAT1 (BRCA1 [breast cancer-1]-associated ataxia telangiectasia mutated activator 1) gene. There are few cases in the literature, and all patients have died before age 2 years, most within the first 6 months of life. The objective of this report is to expand the phenotypic spectrum of BRAT1 disorders and propose new nomenclature for this condition. RESULTS: We describe a child with compound heterozygosity for mutations in BRAT1. Her neonatal course was unremarkable. Over the first year of life she was noted to have progressive global developmental delay, visual impairment, microcephaly, hypertonia, hyperreflexia, and seizures. No epileptiform discharges were seen on electroencephalogram. Serial magnetic resonance imaging of the brain showed progressive cerebellar and brainstem atrophy. Unlike previously described patients, our patient has gained a number of developmental skills and, at this time, is 3 years and 8 months old. CONCLUSION: Despite the name of this disorder, patients with lethal neonatal rigidity and multifocal seizure syndrome may not present until after the neonatal period and may have a much longer life span than previously reported. We suggest renaming the condition "BRAT1-associated neurodegenerative disorder" to avoid the assumptions associated with the original nomenclature and to encourage clinicians to consider this condition outside the neonatal period.

The McMaster Pediatric Migraine Questionnaire: a prospective validation study.

OBJECTIVE: Migraine affects approximately 4%-11% of elementary school children; yet reaching a diagnosis in this age group can be challenging. The goal of this study was to develop a screening migraine questionnaire that could be easily implemented by a general pediatrician and validate its use in diagnosing migraine in children 5-12 years old. METHODS: A questionnaire, the McMaster Migraine Tool, was developed using the International Classification of Headache Disorders-II criteria for migraine. The validity of the questionnaire was assessed by comparing the diagnosis based on the results of the questionnaire compared with the diagnosis made by a pediatric neurologist. RESULTS: The questionnaire was used to assess a cohort of 69 children referred to the Pediatric Neurology Clinic for headache. The sensitivity and specificity of the McMaster Migraine Tool were determined to be 84% and 69%, respectively. Families graded its ease of use to be 9 of 10 (10 being easy to use). CONCLUSION: The McMaster Migraine Tool may be useful in diagnosing migraine in 5-12-year-old children, as it is readily completed and regarded as easy to use. Application of this tool could lead to expedited diagnosis and management of migraine.

Micturition-induced seizures: a rare form of reflex epilepsy.

BACKGROUND: Reflex seizures are referred to as epileptic seizures that are consistently precipitated by a specific sensory stimulus. Reflex seizures induced by micturition are very rare, and few cases have been described. METHODS: This study reports a case of an 11-year-old girl with seizures provoked by micturition with reference made to previously reported cases in the literature. Seizures were characterized by head and eye deviation to the right, flexed dystonic posturing of the left upper limb, extension of the right upper limb, and eventual generalized tonic-clonic seizure. Ictal electroencephalogram revealed clear electrographic evolution from the midcentral region with secondary generalization. Magnetic resonance imaging of the head was normal. Seizures were treated with a combination of lacosamide and clobazam. CONCLUSIONS: A midcentral ictal focus is in keeping with previous reports of this area as a potential epileptogenic center for micturition-induced seizures.

The magnetic resonance imaging appearance of monophasic acute disseminated encephalomyelitis: an update post application of the 2007 consensus criteria.

Acute disseminated encephalomyelitis (ADEM) is an immunologically mediated inflammatory disease of the central nervous system that typically occurs after a viral infection or recent vaccination, and is most commonly seen in the pediatric population. In 2007 the International Pediatric Multiple Sclerosis Study Group proposed a consensus definition for ADEM for application in research and clinical settings. This article gives an overview of ADEM in children, focusing on differences that have emerged since the consensus definition was established. Although the focus is on neuroimaging in these patients, a synopsis of the clinical features, immunopathogenesis, treatment, and prognosis of ADEM is provided.

Neonatal cerebral sinovenous thrombosis: sifting the evidence for a diagnostic plan and treatment strategy.

Although cerebral sinovenous thrombosis (CSVT) is an uncommon disorder in neonates, the incumbent morbidity, mortality, and adverse neurodevelopmental sequelae highlight the importance of establishing an early diagnosis with an appropriate therapeutic plan. The clinical signs and symptoms of the condition are subtle and invariably masquerade under the umbrella of a broad spectrum of neonatal illnesses. A high index of diagnostic suspicion is essential for investigating and initiating treatment in a timely fashion before major complications ensue. Recent advances in accessible radiographic techniques with reduced radiation exposure have facilitated rapid diagnosis of thrombosis in both the superficial and deep plexuses of the cerebral venous systems. The absence of large-scale randomized trials and solid prospective smaller-sample-sized studies of neonates with CSVT has compromised our ability to develop efficacious treatment decisions. In this review of the scientific literature we offer understanding of the complex etiology of CSVT and inherent problems involved in the diagnosis and treatment of the disorder and focus on the limitations in current follow-up. An approach to neonatal CSVT is proposed on the basis of the available evidence from guidelines, registries, prospective and retrospective infant studies, and case series.

The influence of sex on limbic volume and perfusion in AD.

The goal of the current study was to determine whether Alzheimer's disease (AD) pathology affects the limbic system of men and women differently as measured by in vivo neuroimaging. Magnetic resonance imaging (MRI) and coregistered single photon emission computed tomography (SPECT) were used to examine the limbic system in 20 men and 20 women with probable AD compared to 40 age- and education-matched normal controls (20 men, 20 women). Limbic volumes and relative perfusion values were obtained from the MR images and coregistered SPECT scans, respectively. No significant differences were found between sexes in limbic volumes or relative perfusion values in the normal controls. Many limbic regions were significantly affected in both men and women with AD compared to normal controls. However, only the men with AD displayed atrophy in the orbitofrontal cortex, middle and posterior cingulate cortices, hypothalamus, and mamillary bodies, and relative hypoperfusion in the anterior and middle cingulate cortices. Women with AD exclusively showed anterior thalamic atrophy. Separating men and women did not substantially improve diagnostic classification.

Limbic system perfusion in Alzheimer's disease measured by MRI-coregistered HMPAO SPET.

The goal of this study was to perform a systematic, semi-quantitative analysis of limbic perfusion in patients with Alzheimer's disease (AD) using coregistered single-photon emission tomography (SPET) images aligned to magnetic resonance (MR) images. Limbic perfusion in 40 patients with mild to moderate AD was compared with that of 17 age-, sex-, and education-matched normal controls (NC). HMPAO SPET scans and 3D T1-weighted MR images were acquired for each subject. Structures of the limbic system (i.e. hippocampus, amygdala, anterior thalamus, hypothalamus, mamillary bodies, basal forebrain, septal area and cingulate, orbitofrontal and parahippocampal cortices) were traced on the MR images and transferred to the coregistered SPET scans. Perfusion ratios for all limbic regions were calculated relative to cerebellar perfusion. General linear model multivariate analysis revealed that, overall, limbic structures showed significant hypoperfusion (F=7.802, P<0.00001, eta (2)=0.695 ) in AD patients compared with NC. Greatest differences (d > or = 0.8) were found in the hippocampus, as well as all areas of the cingulate cortex. Significant relative hypoperfusion was also apparent in the parahippocampal cortex, amygdala/entorhinal cortex, septal area and anterior thalamus, all of which showed medium to large effect sizes (d=0.6-0.8). No significant relative perfusion differences were detected in the basal forebrain, hypothalamus, mamillary bodies or orbitofrontal cortex. Logistic regression indicated that posterior cingulate cortex perfusion was able to discriminate AD patients from NC with 93% accuracy (95% sensitivity, 88% specificity). The current results suggest that most, but not all, limbic structures show significant relative hypoperfusion in AD. These findings validate previous post-mortem studies and could be useful in improving diagnostic accuracy, monitoring disease progression and evaluating potential treatment strategies in AD.