Chapter
Controversies around the criteria of dissemination in time
MS with an initial ADEM-like episode
Recurrent and multiphasic ADEM versus MS
Differentiation of prepubertal versus postpubertal MS
Lack of a core work-up to rule out mimicking diseases
Section 1: Pediatric MS Diagnosis
Chapter 3: Epidemiology of pediatric multiple sclerosis: incidence, prevalence, and susceptibility risk factors
Retrospective studies: historic difficulties and limitations
Prospective studies, registry- and population-based surveys
Demographic characteristics
Geographic distribution and race
Birth place, place of residency, and role of migration
Family history of demyelinating disorders
Environmental risk factors for childhood MS
Herpesviridae and other neurotropic viruses
Childhood and adolescent obesity
Chapter 4: Clinical presentation of multiple sclerosis in children
Classification of clinical features
Definition of disease onset
Age-related influences on clinical presentation and relapses
Chapter 5: MRI features of pediatric multiple sclerosis
MRI findings in children with MS
Application of adult MRI criteria in children with MS
Proposed MRI criteria for children
Predictive value of MRI for the diagnosis of MS in children
Non-conventional MRI methods
Chapter 6: Differential diagnosis of multiple sclerosis and acquired central nervous system demyelinating disorders in children and adolescents
Systemic inflammatory disorders
Systemic lupus erythematosus (SLE)
Primary or isolated CNS vasculitis
Human immunodeficiency virus (HIV)
Progressive multifocal leukoencephalopathy (PML)
Neuroborreliosis (Lyme disease)
Adrenoleukodystrophy (ALD)
Metachromatic leukodystrophy (MLD)
Pelizaeus-Merzbacher disease (PMD)
Childhood ataxia with diffuse CNS hypomyelination (vanishing white matter disease)
Migraine and hemoglobinopathies
Other rare vasculitides involving the CNS in children
Other disorders leading to MRI brain abnormalities
Differential diagnosis key points
Section 2: Pediatric MS Course and Treatment
Chapter 7: Pediatric multiple sclerosis course and predictive factors
Methodological considerations
Disease onset (clinical, biological, radiological)
Biological findings at onset
Magnetic resonance imaging (MRI) findings at onset
Symptom severity at disease onset
Symptom recovery at disease onset
Time from onset of MS to the second neurological episode (including predictors of a shorter time to second episode)
Relapses (including relapse rate, location, and recovery)
Evolution to the secondary progressive phase
Time to secondary progression
Prognostic factors of secondary progression (clinical, paraclinical)
Influence of environmental and genetic factors on the course of the disease
Methodological considerations
Development of irreversible disability
Time to disability milestones (limitation of ambulation, use of assistive devices)
Prognostic factors of disability (clinical, paraclinical)
Development of cognitive problems
Chapter 8: Plasma exchange and IV immunoglobulin for acute demyelinating relapses
Chapter 9: Corticosteroids in pediatric multiple sclerosis relapses
Chapter 10: Disease-modifying therapy and response to first-line treatment in pediatric multiple sclerosis
First-line disease-modifying therapies in pediatric MS
Chapter 11: Treatment of breakthrough disease
Goals of breakthrough therapy in pediatric MS
Definition of breakthrough disease
Second-line drugs approved in adult MS
Drugs approved in other indications
Interferon beta and glatiramer acetate
Interferon beta and methylprednisolone
Interferon beta and azathioprine
Interferon beta and mitoxantrone
Interferon beta and natalizumab
Chapter 12: Symptomatic therapy in pediatric multiple sclerosis
Evaluation and care of patients with visual abnormalities
Internuclear ophthalmoplegia (INO)
Evaluation of visual function
Management of visual dysfunction
Non-pharmacologic interventions for visual dysfunction
Pharmacologic management of visual symptoms
Evaluation and care of speech and swallowing difficulties
Evaluation and management of motor, gait, and coordination difficulties
Gait and coordination difficulties
Evaluation of motor and coordination abnormalities
Standardized test for upper extremity function/coordination
Management of motor and coordination difficulties
Non-pharmacologic treatment for spasticity
Pharmacologic treatment of spasticity
Non-pharmacological intervention
Pharmacological treatment of ataxia and tremor
Evaluation and care of bladder and bowel symptoms
Evaluation and management of the neurogenic bladder
Evaluation and care of the neurogenic bowel
Sensory symptoms - pain and paroxysmal symptoms
Management of specific pain syndromes
Systemic symptoms - heat intolerance, fatigue, and mental health issues
Fatigue related to symptomatic therapy
Chapter 13 Cognitive dysfunction in pediatric-onset multiple sclerosis
Prevalence, pattern, and clinical correlates of cognitive impairment in POMS
The longitudinal course of cognitive functioning in POMS
Neuropsychological assessment techniques to detect cognitive impairment in POMS
Considerations for testing and interpretation
Impact of cognitive function on functional activities
Neuropsychology and future directions in POMS
Chapter 14: Living with pediatric multiple sclerosis: patient well-being
Health-related quality of life in multiple sclerosis
Health-related quality of life in adult-onset MS
The impact of pediatric MS on health-related quality of life
Pediatric multiple sclerosis and school
The impact of cognitive functioning on school
Social-emotional functioning in school
Accommodation/intervention
Psychosocial aspects of pediatric multiple sclerosis
The psychosocial impact of pediatric MS
Signs of psychosocial distress
Unexplained medical complaints
Improving psychosocial function in pediatric MS
Transitioning to adult care
Improving the well-being of children with multiple sclerosis
Section 3: Pediatric MS Biology
Chapter 15: Pediatric MS: biological presentation and research update
Distinguishing features of the pediatric immune system
T-cell responses and studies
B cell and antibody responses
Environment impacting pediatric MS disease biology
Responses to infectious agents
The need for biomarkers of inflammation and neurodegeneration
Chapter 16: Genetics of pediatric multiple sclerosis
Genes versus family environment
Autoimmune diseases in families
Molecular genetic studies in pediatric MS (Group 1)
The major histocompatibility complex
Epigenetic interactions within the HLA locus
The first neuronal risk genes
Single gene disorders that mimick MS
Chapter 17: Clinical and biological features of acute disseminated encephalomyelitis
Acute hemorrhagic leukoencephalitis
Outcome in ADEM and further episodes of demyelination
Monophasic ADEM, recurrent ADEM, and multiphasic ADEM
Distinguishing ADEM from CIS and MS
Definitions of CIS and MS
Clinical and neuroimaging distinctions
Risk of developing MS after an initial acute demyelinating event
Pathology and immunopathology of ADEM
Chapter 18: MRI features of acute disseminated encephalomyelitis
MRI of ADEM: lessons from early reports
Lesion characteristics of ADEM
T1-weighted characteristics (black holes)
Lesion regional involvement
Spinal involvement in ADEM
Tumefactive or ``tumor-like´´ lesions
Bithalamic or bistriatal ADEM
Acute hemorrhagic leukoencephalitis (AHLE)
Proposed new MRI diagnostic criteria for ADEM
MRI outcome of ADEM lesions, and timing of repeat imaging
Differential diagnosis of radiological ADEM
Chapter 19: Treatment and prognosis of acute disseminated encephalomyelitis
Treatment of the acute phase of ADEM with high doses of corticosteroids
Corticosteroid treatment and the risk of subsequent relapses
Other therapies for the acute phase of ADEM, especially in life-threatening situations
Repetition of intravenous methylprednisolone
Intravenous immunoglobulin
Section 5: Optic Neuritis in Children
Chapter 20: Pediatric optic neuritis
Clinical features of pediatric optic neuritis
Differential diagnosis and evaluation
Treatment of acute optic neuritis
Prognosis after optic neuritis in childhood
Chapter 21: Recurrent isolated optic neuritis in the pediatric population
Recurrent ON in the pediatric population
Recurrent ON and NMO-IgG antibodies
Optical coherence tomography in RON
Conclusions and future directions
Section 6: Acute Complete Transverse Myelitis in Children
Chapter 22: What is acute transverse myelitis in children?
Overlap of ATM with MS and related diseases
Clinical presentation of ATM
Preceding illness or immunization: a controversial notion
Diagnostic evaluation and differential diagnosis of sudden spinal cord dysfunction
Extraspinal differential diagnosis
Intraspinal conditions other than ATM
ATM vs. ADEM vs. CIS and MS
Acute interventions and medical treatments
Section 7: Neuromyelitis in children
Chapter 23: Neuromyelitis optica in children
Aquaporin-4: the target autoantigen in NMO
The historical perspective
Current diagnostic criteria
Cerebrospinal fluid findings
Co-existing autoimmune disorders and autoantibodies in NMO
Disease course and outcome
Demyelinating Disorders of the Central Nervous System in Childhood
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