NEURODEGENERATIVE

DISORDERS
(NDD)
IN
CHILDREN

CASE-BASED NEURODISCUSSION SERIES with Dr.Lakshmi Achar

Dr.Mohan.T.Shenoy

2nd yr Postgraduate student

KIMS Hospital,Bangalore,India
Neuro Discussion with Dr.Lakshmi2Achar
NeuroDiscussion with Dr.Lakshmi Achar 3
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 Leukodystrophies in children
• Introduction

• Myelin structure & Myelination

• Concepts of Leukoencephalopathies & Leukodystrophies

• Approach to diagnosis

• Summary of common leukodystrophies

• Mimics of Leukodystrophies
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 Leukodystrophies
Greek word

Leuko = White
Dys = ill
Trophy = Growth

“Describes a set of diseases that affect the growth or

maintenance of the white matter (myelin)”

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 Myelin disorders : Definitions
• Delayed myelination
“Deposition of myelin is delayed but progressing . . .”

• Dysmyelination
“The process of myelination itself is disturbed leading to abnormal patchy & irregular
myelination” E.g. Aminoacidopathies

• Demyelination
“Primary & selective abnormality of either oligodendroglia / myelin membrane”

• Hypomyelination
“Conditions with significant permanent deficit in myelin deposit”
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 Leukodystrophies
• Includes a wide spectrum of disorders

• Data on incidence, disease burden & outcome measures- sparse

• Overall population incidence in a recent study: 1 in 7663 live births

• Almost half of the patients remain undiagnosed !!

• Poses problems in prognostication, genetic counseling & prenatal

diagnosis

Bonkowsky et al. Neurology 2010;75:718-725 9

 Myelin disorders:Definitions
Leukoencephalopathies

“All disorders that selectively or predominantly involve the white

matter of the CNS irrespective of the underlying pathophysiologic
mechanisms or histopathologic basis”

Leukodystrophies

“Group of genetically determined disorders with progressive

demyelination”
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 Myelin structure & Function

•Major component of the white matter

•Modified plasma membrane of

oligodendroglia

•One cell contributes to around 50 axons

•Wrapped in a spiral fashion around a

portion of an axon to form a sheath

NeuroDiscussion with Dr.Lakshmi Achar

 Myelination
• Myelination - Complex process

• Timing
• Begins ~ 2nd trimester.
• Adult pattern ~ 2 years age.
• Continues – Life long.

– Close interaction between

• oligodendrocytes,
• axons,
• astrocytes,
• many soluble factors.
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 Myelination Rules
• Myelination progresses from

– Caudal to rostral parts

– Central to peripheral part
– Anterior to posterior
– Sensory to motor

Tracts become myelinated at the time they become functional

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 Myelin disorders

• Myelin disorders may result from dysfunction of

– Oligodendrocyte
– Myelin membrane
– Neurons
– Astrocytes

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 Classification
• Lysosomal disorders

• Peroxisomal disorders

• Disorders of amino acids and organic acid metabolism

• Mitochondrial dysfunction with leukoencephalopathy

• Nuclear DNA repair defects

• Defects in gene encoding myelin proteins

• Miscellaneous
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• Metachromatic Leukodystrophy

• Krabbe's leukodystrophy

• Pelizeus Merzbacher disease

• Canavan's disease

• Alexander's disease

• Megalencephalic leukodystrophy with subcortical cysts

• Vanishing white matter disease 16