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 Hamouda - PowerPoint PPT PresentationTRANSCRIPT
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
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
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.
• 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
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
8/9
7/9
Results
• 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
0
2
4
6
8
10
12
Typical signs
Atypical signs
Results
Examination
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
T2 hyperintensity of the supratentorial white matter, and displaying the radial stripes pattern
U fibers spared U fibers involved
T2 hyperintensity of the posterior limb of the internal capsule
and the pyramidal tract within the crus cerebriT2 hyperintensity of the cerebellar white matter,
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
Corpus callosum involvement
genu T2 hyperintensitysplenium T2 hyperintensity
atrophy
Results
• CSF analysis : hyperproteinorachia: 9/9
• NCV Studies: demyelinating neuropathy: 9/9
• Arylsulfatase A activity : very low : 8/8
Investigations
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
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
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.
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
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
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
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
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
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
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