C. Drissi, I. Kraoua *, I. Rebaï *, S. Nagi , N. Gouider - Khouja *, M. Ben Hamouda
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Transcript of C. Drissi, I. Kraoua *, I. Rebaï *, S. Nagi , N. Gouider - Khouja *, M. Ben Hamouda
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Imaging and clinical features of metachromatic leukodystrophy:
a study in 9 Tunisian children
C. Drissi, I. Kraoua*, I. Rebaï*, S. Nagi, N. Gouider-Khouja*, M. Ben HamoudaNeuroradiology and * * Pediatric Neurology Departments –National Institute of Neurology – Tunis – Tunisia PEDIATRICS : PD 19
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Introduction
• Metachromatic leucodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by deficiency of arylsulfatase A activity resulting in demyelination within the central and peripheral nervous system.
• 3 clinical forms: – Late-infantile (<3 years)– Juvenile (<16 years)– Adult (>16 ans)
Costello et al ,2009
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Objective
• The aim of this study is to describe the imaging and clinical features of MLD in 9 Tunisian children.
• The results are analyzed and discussed with a literature review.
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• Retrospective study (2005-2011)• 9 children from 8 families with confirmed MLD • Followed in the department of Pediatric Neurology at
the National Institute of Neurology of Tunis • Brain MRI was performed in all cases• Imaging and Clinical data are analyzed
Patients and methods
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Results
• 9 children : 2 / 7 ♂ ♀
• Mean age: 32 months (17 months – 6 years)
• 8 patients with late infantile MLD with a mean age at onset of 16 months
• One patient with a juvenile form with age at onset of 4 years
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8/9
7/9
Results
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• Psychomotor regression: 8/9• Irritability : 8/9• Epilepsy : 3/9 (uncontrolled in one case)• Learning disabilities and gait disturbance: 1 case
(juvenile form)
Results
Clinical presentation
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Typical signs
Atypical signs
Results
Examination
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Results
• Brain MRI showed bilateral symmetric areas of T2 hyperintensity involving supra-tentorial deep white matter in 8 cases, sparing U fibers in most cases (6/8).
• In all of these 8 cases, a pattern of radial stripes was seen.
• In 2 cases, it also involved cerebellar white matter, the posterior limb of the internal capsule and the pyramidal tract within the crus cerebri.
MRI
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T2 hyperintensity of the supratentorial white matter, and displaying the radial stripes pattern
U fibers spared U fibers involved
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T2 hyperintensity of the posterior limb of the internal capsule
and the pyramidal tract within the crus cerebriT2 hyperintensity of the cerebellar white matter,
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Results
• Corpus callosum was involved in all cases, atrophic in one case and presenting with a hyperintensity in all other 8 cases.
• The hyperintensity involved the splenium in 5 cases, the genu in 1 case and the entire corpus callosum in 1 case.
• Severe cortical atrophy was seen in one case.
MRI
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Corpus callosum involvement
genu T2 hyperintensitysplenium T2 hyperintensity
atrophy
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Results
• CSF analysis : hyperproteinorachia: 9/9
• NCV Studies: demyelinating neuropathy: 9/9
• Arylsulfatase A activity : very low : 8/8
Investigations
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Metachromatic leukodystrophy MLD
• Incidence 0.6 – 1.85 / 100.000 live birth
• Pathophysiology3-O-sulfogalactosylceramide galactosylceramide
• Sulfatides accumulation and oligodendrocytes death• Demyelination of central and peripheral nervous system
Arylsulfatase A (ASA)
X(sulfatide)
Arvan et al, 2011
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MLD
3 clinical forms
Clinical form Late infantile Juvenile Adult
Age at onsetyeras
2nd year(< 3 )
3 – 16 > 16
Presentation Psychomotor regression, irritability
Learning disabilities, behavior disorders
Dementia« schizophrenia »
Examination Pyramidal signs, hypertonia, abolished deep tendon reflexes, optic atrophy
Pyramidal signs, ataxia dementia
Outcome death
2 – 6 years 10 – 20 years 30 ans
Arvan et al, 2011
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MLD
MRI• Periventricular WM abnormalities,with a more or
less symmetrical distribution. • The white matter lesions are highly confluent.• In later onset cases involvement is often
predominantly frontal, whereas in early-onset cases occipital predominance can be observed.
• The arcuate fibers are relatively spared, but become involved in the later stages.
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MLD
MRI
Typically a pattern of radiating stripes– lysosomal storage disorders
(Krabbe, GM1)– relative myelin sparing?– lipid storage?
Van der Voorn et al, AJNR, 2005
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MLD
• Probably the first abnormalities to be noted on MRI are in the corpus callosum (CC).
• CC is always affected, connecting the lesions from both sides.
MRI
T2 hyperintensity of the splenium of the CC in the unique case without involvement of WM
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MLD
MRI
• Cerebral WM atrophy occurs in advanced stages. • Some patients show bilateral involvement of :– the posterior limb of the internal capsule,– the cerebellar white matter,– pyramidal tracts in the brain stem, especially in the more
advanced cases. • No contrast enhancement is seen.• A MR severity scoring method has been proposed by
Eichler et al.Eichler F et al, AJNR, 2009
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MLD
MRI
• Diffusion weighted-imaging :– Hyperintensity with low ADC values
in deep white matter• MR-Spectroscopy:– decreased choline peak– Myoinositol peak– Lactates
Sener RN,AJNR, 2002Sener RN, Acta Radiologica 2003
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MLD
CSF : hyperproteinorachia
NCV studies : demyelinating neuropathy
Biochemical diagnosis : ASA activity+++
Molecular diagnosis: 22q13.3-qter, ARSA gene > 100 mutations Genotype / phenotype correlation
Diagnosis
Groeschel et al, 2011
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MLD
• Symptomatic forms: symptomatic treatment
• Presymptomatic forms:
Hematopoietic stem cell transplantation
Clinical research: gene therapy, enzyme replacement therapy
• Genetic counselling
Treatment
Batzios et al, 2012; Biffi et al, 2011Gieselmann et al, 2011
Arvan et al, 2011
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Conclusions
• Imaging features in MLD are non specific but can be highly suggestive in children presenting with psychomotor regression
• The diagnosis, confirmed by specific biological tests, allows genetic counseling