Mimics and rare presentations of pediatric demyelination.

This article reviews the features that should prompt consideration of diseases that mimic acquired demyelinating syndromes and multiple sclerosis using vignettes to highlight unusual clinical and radiologic features. Cases of transverse myelitis, spinal infarction, acute disseminated encephalomyelitis, fever-induced refractory epileptic encephalopathy in school-aged children, small-vessel vasculitis, Griscelli syndrome type 2, cysticercosis, vitamin B12 deficiency, and chronic relapsing inflammatory optic neuropathy are presented.

Diagnosing neuromyelitis optica.

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disorder typically characterized by attacks of recurrent optic neuritis and transverse myelitis. Advances in magnetic resonance imaging techniques and the discovery of the relatively specific NMO IgG biomarker have led to improved diagnostic accuracy and greater recognition of the broad clinical spectrum of aquaporin 4-related autoimmunity. Brain lesions in NMO typically follow the distribution of aquaporin 4 expression and may be symptomatic.

Pediatric multiple sclerosis: pathobiological, clinical, and magnetic resonance imaging features.

In this article, the pathobiological, clinical, and treatment aspects of pediatric-onset multiple sclerosis (MS) are summarized, and the conventional magnetic resonance (MR) imaging (ie, T1-weighted, proton-density, and T2-weighted imaging) features of MS in children are discussed, as well as the application of MR imaging in the diagnosis of pediatric-onset MS and in prediction of MS in children with an incident central nervous system demyelination. Insights gained from studies comparing MR imaging features of pediatric-onset and adult-onset MS are presented.

Standardized magnetic resonance imaging acquisition and reporting in pediatric multiple sclerosis.

Magnetic resonance (MR) imaging is one of the most important paraclinical tools for the diagnosis of multiple sclerosis (MS), and monitoring of disease progression and treatment response. This article provides clinicians and neuroradiologists caring for children with demyelinating disorders with a suggested standard MR imaging acquisition and reporting protocol, and defines a standard lexicon for lesion features typical of MS in children. As there is considerable overlap between the MR imaging features of pediatric- and adult-onset MS, the recommendations provided herein may be of relevance to radiologists and clinicians caring for adults with multiple sclerosis.

Treatment optimization in MS: Canadian MS Working Group updated recommendations.

The Canadian Multiple Sclerosis Working Group (CMSWG) developed practical recommendations in 2004 to assist clinicians in optimizing the use of disease-modifying therapies (DMT) in patients with relapsing multiple sclerosis. The CMSWG convened to review how disease activity is assessed, propose a more current approach for assessing suboptimal response, and to suggest a scheme for switching or escalating treatment. Practical criteria for relapses, Expanded Disability Status Scale (EDSS) progression and MRI were developed to classify the clinical level of concern as Low, Medium and High.

International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions.

Background: There has been tremendous growth in research in pediatric multiple sclerosis (MS) and immune mediated central nervous system demyelinating disorders since operational definitions for these conditions were first proposed in 2007. Further, the International Pediatric Multiple Sclerosis Study Group (IPMSSG), which proposed the criteria, has expanded substantially in membership and in its international scope.

Objective: The purpose of this review is to revise the 2007 definitions in order to incorporate advances in delineating the clinical and neuroradiologic features of these disorders.

Changes in cognitive performance over a 1-year period in children and adolescents with multiple sclerosis.

Objective: Cognitive impairment is a core symptom of pediatric-onset multiple sclerosis (MS), although relatively little is known regarding the rate of cognitive decline. This study examined the extent, pattern, and correlates of change in cognitive functioning in youth with MS.

Method: Changes in cognitive performance in 28 patients with pediatric-onset MS and 26 age-matched controls were ascertained through repeat comprehensive neuropsychological assessment conducted over a 1-year period.

International Pediatric MS Study Group Clinical Trials Summit: meeting report.

Objective: Pediatric studies for new biological agents are mandated by recent legislation, necessitating careful thought to evaluation of emerging multiple sclerosis (MS) therapies in children with MS. Challenges include a small patient population, the lack of prior randomized clinical trials, and ethical concerns. The goal of this meeting was to assess areas of consensus regarding clinical trial design and outcome measures among academic experts involved in pediatric MS care and research.

Development of a standardized MRI scoring tool for CNS demyelination in children.

Background And Purpose: The degree to which MR imaging is useful in the diagnosis of MS is predicated on standardized and reliable evaluation of MR imaging parameters. We aimed to devise items for an MR imaging scoring tool that would have high inter-rater agreement and would be straightforward to apply.

Materials And Methods: On the basis of a literature search and consensus of an expert panel, we identified 48 parameters that describe acute CNS demyelination, predict MS diagnosis, or characterize demyelinating disorder mimics.

Cognitive and behavioral outcomes in individuals with a history of acute disseminated encephalomyelitis (ADEM).

We describe cognitive and behavioral outcomes in 12 males and 7 females diagnosed with acute disseminated encephalomyelitis (ADEM) in childhood. Age at assessment ranged from 6 to 23 years and all participants were at least 2 years post-ADEM presentation (mean 5.4 years).

Cognitive trajectories in 4 patients with pediatric-onset multiple sclerosis: serial evaluation over a decade.

Cognitive dysfunction is common in pediatric-onset multiple sclerosis, but long-term data on cognitive maturation in these patients are sparse. We report the clinical features and cognitive trajectories in 4 pediatric-onset multiple sclerosis patients who were 10 years or younger at first attack and were followed between 1998 and 2010. Relapses in all 4 patients were frequent early in the disease and became infrequent or absent over time.

2010 McDonald criteria for diagnosing pediatric multiple sclerosis.

Objective: The diagnosis of multiple sclerosis (MS) rests on confirmation of central nervous system inflammatory disease that is disseminated in space and time, as evidenced clinically or by magnetic resonance imaging (MRI). The 2010 McDonald criteria simplified MRI requirements, and newly proposed that the criteria are also suitable for the diagnosis of pediatric MS.

Methods: In a national prospective incident cohort study of children with acute demyelination observed for a minimum of 24 months, baseline and serial clinical and MRI examinations were used to retrospectively evaluate the 2010 and 2005 McDonald criteria using clinically relapsing disease as the gold standard.

Pediatric multiple sclerosis.

Pediatric multiple sclerosis has been increasingly recognized in the past 10 to 15 years; 3% to 5% of all multiple sclerosis patients experience their first attack in childhood. Childhood multiple sclerosis has a relapsing-remitting disease course. The first attack, or "acquired demyelinating syndrome," consists of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and monofocal or polyfocal neurological deficits.

Magnetic resonance imaging predictors of executive functioning in patients with pediatric-onset multiple sclerosis.

Executive functions (EFs) are vulnerable to disruption in pediatric-onset multiple sclerosis (MS) patients. We describe the pattern and correlates of executive dysfunction in 34 adolescents with MS on neuropsychological tests and the parent version of the Behavior Rating Inventory of Executive Function (BRIEF). The adolescents with MS performed lower than age-matched controls in several areas of executive functioning, with 44% of patients being impaired on the Trail Making Test-Part B.

Autoantibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein in paediatric CNS demyelination: Recent developments and future directions.

Diagnosis and prognosis of acute inflammatory disorders of the central nervous system in both children and adults would be aided by the availability of serum biomarkers. Antibodies directed against the aquaporin-4 water channel has led to recognition of neuromyelitis optica (NMO) and NMO spectrum disorders in both children and adults and to the ability to predict a relapsing disease course in antibody-positive patients. Serum antibodies directed against myelin antigens are detectable in approximately one third of children with acute disseminated encephalomyelitis (ADEM) at the time of acute illness, and in approximately 25% of children with multiple sclerosis (MS) in whom seropositivity persists.

Masquerades of acquired demyelination in children: experiences of a national demyelinating disease program.

The diagnosis of acquired demyelinating syndromes of the central nervous system in children requires exclusion of other acute central nervous system disorders. In a 23-site national demyelinating disease study, standardized clinical, laboratory, and magnetic resonance imaging (MRI) data were obtained prospectively from onset, and serially at 3, 6, and 12 months and annually. Twenty of 332 (6%) participants (mean [SD] age, 10.

Implication of perturbed axoglial apparatus in early pediatric multiple sclerosis.

Cerebrospinal fluid samples collected from children during initial presentation of central nervous system inflammation, who may or may not subsequently be diagnosed as having multiple sclerosis (MS), were subjected to large-scale proteomics screening. Unexpectedly, major compact myelin membrane proteins typically implicated in MS were not detected. However, multiple molecules that localize to the node of Ranvier and the surrounding axoglial apparatus membrane were implicated, indicating perturbed axon-glial interactions in those children destined for diagnosis of MS.

Memory performance and normalized regional brain volumes in patients with pediatric-onset multiple sclerosis.

Studies in adults with multiple sclerosis (MS) have associated regional brain abnormalities with memory impairment. While memory problems in children with MS are often reported, little is known about the neural correlates that may contribute to these difficulties. We measured verbal and nonverbal memory using the Test of Memory and Learning (TOMAL-2) in 32 children and adolescents with MS and 26 age- and sex-matched healthy controls.

Factors associated with emotional and behavioral outcomes in adolescents with multiple sclerosis.

Background: Multiple sclerosis (MS) onset during adolescence has the potential to disrupt a key period of psychosocial maturation.

Objective: We aimed to examine the prevalence and risk factors associated with emotional and behavioral outcomes in adolescents with MS.

Methods: The Behavioral Assessment System for Children-2nd Edition (BASC-2) was completed by 31 adolescents with MS (mean age = 16.