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Neurology
Robert Carson MD PhD
Pediatric Neurology Resident Lecture Series
DOT 8155
09.13.2013
Goals
Review
development of Myelin
Discuss Normal Myelin Imaging
Outline an approach to
Leukodystrophies
inflammatory disorders
of CNS
Myelin basic science (2 weeks)
My groundbreaking research in
exquisite detail :^(
White matter in
neurodevelopment.
Abnormal
Autism
TSC
Angelmans
Periventricular
leukomalacia
(spike-timing
dependent plasticity)
(Nave, K. 201
T1
General Patterns of
myelination
Rostral
to caudal
Posterior to anterior
Central to peripheral
T1
T2
T1
FLAIR
T1
T2-FSE
FLAIR
T2-FSE
T1
T2-FSE
FLAIR
T2-FSE
T1
T2-FSE
FLAIR
T2-FSE
FLAIR
T2-FSE
FLAIR
T2-FSE
Normal Variant
FLAIR
FLAIR
T2-FSE
T2-FSE
9m
15m
2y
3y
Terminal Zones of
myelination
Components of myelin:
Sheath:
protein-lipid-protein-lipid-
protein
Glycolipids: glalctocerebroside,
sulfatide, cholesterol
Outer layer of membrane
Long
Leukodystrophies
Genetic,
Leukoencephalopathies:
defects
causing secondary myelin damage
Diagnosis
Clinical presentation
Insiduous,
in a previously healthy
child.
Slowly progressing, may have
periods of stagnation
Vague/progressive motor and
mental symptoms.
Widely variable phenotypes
associated with single genetic
disease
Presents from infancy to
Age of onset
Exam
Physical
abnormalities uncommon
(progressive):
Motor (spasticity)
Changes in cognition and language
Seizures are rare
Peripheral nerve (MLD, globoid cell,
hypomyelination)
approach:
1. Hypomyelination?
Tigroid
appearance
MLD
Globiod cell
Sparing
fibers
X-ALD
MLD
of U-
Nearly pathognomonic
Alexander
disease
Contrast enhancement if an
inflammatory component
Additional imaging
MRS
Globoid cell
leukodystrophy
Swelling
of optic
nerves
Contrast
enhancement of
spinal roots
+/- peripheral
nerve thickening
Electrophysiology
NCS
potentials
Tests
to
consider early
on in
evaluation.
Low yield of
done prior to
exam and
evaluation of
imaging.
Cataracts
Cerebrotendinous xanthomatosis
Some forms of hypomyelination
Endocrine
Treatment
Prognosis
is dismal
Supportive care
Swallow eval/g-tube
Abx when indicated
Antispasmodics and pain control.
ACTH monitoring/stress dose steroids
Treatment Continued
Lorenzos
oil in X-ALD
Marrow transplantation
therapy
Experimental
Therapeutic window is narrow
Asymptomatic____ Too far gone
Leukodystrophies, in
Summary:
Incurable
Summary continued,
Diagnosis
through:
Physical examination
MRI imaging
With help from targeted laboratory
testing
Important
References
Welker
Kohlshutter
and Eichler.
Childhood leukodystrophies: a
clinical perspective. Expert Rev.
Neurother. 2011;11:1485-1496.