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The central role of the immune system
in several pediatric central nervous system (CNS) disorders has
been increasingly appreciated in recent years. Although relatively
rare as individual diseases, collectively they constitute a sizable
proportion of pediatric neurology practice. The acute, severe symptoms
associated with these disorders usually lead to inpatient hospitalization.
Due to the broad differential diagnoses associated with these conditions,
multiple other pediatric subspecialists, such as infectious disease
and rheumatology physicians, are often asked to evaluate affected
patients. Last, because of the potential long-term sequelae of both
the monophasic and recurrent immune-mediated CNS disorders, all
aspects of a patient’s medical and psychosocial care can
be affected. Thus, these disorders have relevance to general pediatricians
and pediatric subspecialists in both the inpatient and outpatient
settings.
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Demyelinating disorders comprise the largest subgroup within
CNS immune-mediated disorders. Myelin is composed of a lipid bilayer
of cholesterol, phospholipids, and glycolipids along with membrane-associated
proteins, such as proteolipid protein and myelin basic protein.1,2 In
the CNS, oligodendrocytes produce myelin, which surrounds axons
with periodic interruptions at nodes of Ranvier. The main functions
of myelin are to speed the conduction of action potentials along
axons and to support the development and maintenance of axons.
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Myelin can be injured by many different mechanisms, such as hypoxia,
metabolic derangements, and toxic insults. The disorders discussed
in this chapter are considered to have an autoimmune etiology, with
loss of tolerance resulting in an aberrant, self-reactive inflammatory
process directed against CNS myelin.
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Demyelination leads to slowing or blockade of action potential
propagation, with resulting symptoms referable to the affected CNS
areas. Although remyelination can occur in the CNS, the thickness
of the original myelin sheath is never reachieved.3 Demyelination
can also lead to secondary axonal loss, which leads to permanent
disability.4
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First Attack
of Demyelination
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Definitions,
Terminology, and Classification
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In the past, variable terminology and lack of consistent definitions
in the literature hampered our understanding of pediatric CNS demyelinating
disorders. In April 2007, diagnostic definitions were proposed by
the International Pediatric Multiple Sclerosis (MS) Study Group.5 Although
they have not yet been prospectively validated, these definitions
provide a very useful framework both for clinical and research purposes.
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With a first presentation of a CNS demyelinating disorder, determining
whether mental status changes are present or absent serves as the
initial step in classification (Fig. 556-1). When
present and accompanied by multifocal symptoms, the appropriate
diagnosis is acute disseminated encephalomyelitis (ADEM), which
can be confirmed with magnetic resonance imaging (MRI). When the
patient’s mental status is normal, first-time acute demyelinating
events are collectively referred to as clinically isolated syndromes
(CIS). Clinically isolated syndromes can be subdivided based on
whether the symptoms and signs are focal or multifocal. Common locations
for focal CIS include the optic nerve (optic neuritis), spinal cord
(transverse myelitis), brain stem, and ...