Transcript Pathologies de la substance blanche chez l'enfant - UVT e-doc

Pathologies de la substance
blanche chez l’enfant
Dr. Kalthoum TLILI-GRAIESS
Master Neuroradiologie
FMS Avril 2008
Children WM Disorders
• Genetic disorders affecting WM in pediatric age
• Acquired pathologies : inflammatory, auto-immune, tumoral or
vascular diseases.
Although uncommon, aware of their occurence and able to recognize
MR appearances.
• MR imaging is highly sensitive in the detection of WM lesions
• Limited specificity with regards to the pathologic conditions
underlying WM signal abnormalities
• Correct diagnosis need multidisciplinar approach :
– clinical history Data
– Findings laboratory Data
Herpetic meningo-encephalitis
Cerebral Abscess
Childhood WM Disorders : MR approach
• Variable pathologic changes may underlie WM signal
abnormalities
– Hypomyelination
– dysmyelination
– Demyelination
– Gliosis
– Interstitial edema
– Myelin vacuolation
– Cystic WM degeneration
– Diffuse infitration by tumors cells (Gliomatosis)
• All types : lead to a non specifically
– increase signal intensity T2 WI,
– discrease signal intensity T1 WI
Childhood WM Disorders : MRI
• « Morphological » sequences
• « Functional » or parametric sequences and
techniques:
– Evaluation WM biochemistry: MRS
– Evaluation WM tissue microstructure: diffusion and
Magnetization transfer sequences
May provide new insights.
Children WM Disorders
• Demyelinating lesions
– Primary disorders : ADEM, MS
– Secondary disorders : Toxic, Viral….
• Hyo and dysmyelinating lesions: more common primary
disorders Classified according to causative enzyme defect
– Lysosomal storage diseases: metachromatic
leucodystrophy, Krabbe disease…
– Peroxisomal disorders: Zellweger syndrome , ADL X..
– Mitochondrial syndromes : leigh syndrome, Kearns – Sayre
syndrome, MELAS…
Genetic WM Disorders
• Well defined leucoencephalopathies
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Hypomyelinating disorders
Dysmyelinating disorders
Leucodystrophies
Disorders related to cystic degeneration of myelin
Disorders secondary to axonal damage
• Undefined leucoencephalopathies
– Up to 50 % of leucoencephalopathies in childhood
– Requiring multidisciplinar approach in order to define novel
homogenious subgroups of patients and therefore « new genetic
disorders »
Megalencephaly-leucoencephalopathy with sub cortical cysts (1995),
CACH Sydrome or Vanishing WM disease (1997) Van der Knaap
Leucoencephalopathy with high brain lactate.
Genetic WM Disorders
• Characteristic MR pattern : Metachromatic
leucodystrohy, ALDX, Canavan disorder…
• Role of MR techniques in the discrimination of
differents WM disorders: Parametic imaging.
Metachromatic leukodystrophy
Classic: Sparing of the subcortical U fibers
and periventricular WM. Tigroid pattern
Frequent involvement: CC,IC, corticospinal
tracts
Krabbe disease
Early-onset form: pyramidal tract,
periventricular WM, cerebellar WM,
and deep gray matter ,
The most often affected
Adrenoleucodystrophy, X linked ALD
Symmetric WM demyelination in peri-trigonal regions
Extendion across the corpus callosum splenium
Spread outward and cephalad
Symmetric abnormal signal internal capsule, deep cerebelar WM
and descending pyramidal tract
(1) Cheon JE et al, Radiographics 2002;22:461
TE 35
TE 144
TE 35
TE 144
Pelizaeus-Merzbacher Disease
Megalencephaly and abnormal WM
• Canavan disease
• L -2-hydroxyglutaric Aciduria
• Megalencephaly-leucoencephalopathy with sub cortical
cysts
• Alexander disease
Diagnosis relay on neuroimaging and biochemical findings
Canavan disease
TE 35
TE 144
Predominant subcortical WM and dentate nuclei lesions
Variable basal ganglia involvement
Typical brainstem involvement
L -2-hydroxyglutaric Aciduria
• Similarities with Canavan except
brainstem involvement
• SRM
Megalencephaly-leucoencephalopathy with sub cortical cysts.
Van der Knaap 1995
Mehdi 11years-old
and 3SD
Naim 13 years-old
and 4 SD
Syrine 7 years-old
and 2.5 SD
Mutation MLC1 gene although
variable phenotype
Megalencephaly-leucoencephalopathy with sub cortical cysts
Cerebral WM involvement in Mitochondrial
disorders
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Major findings : Alteration of basal ganglia and Brainstem
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Demonstrated that severe WM involvement is possible (1,2) and
even the only abnormal neurologic features (3) : 3 unrelated
families / 5
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Suggestive findings of mitochondria disease :
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Multiples small cyst-like lesions in the abnormal WM
Involvement of cerebral and cereberal WM
Combination of Leucoencephalopathy and bilateral basal ganglia lesions
MRS : may demonstrate lactate or succinate peak
(1) Valannel et al AJNR 1998 ; 19 : 369
(2) Nakai A et al Lancet 1994; 343 : 1397
(3) de Lonlay – Debeney P et al J Pediatric 2000 ; 136 : 209
Leigh disease
13 months-old. Complexe II deficiency
8 month-old child, Axial hypotonia
Mitochondrial disease
•16 months-old girl with one week respiratory distress
•At the age of 9 months progressive loss of normal developmental and motor
acquisitions with sudden alopecia and global hypotonia
•Mild optic atrophy
•Brain stem acoustic-evoked
potentials were deteriorated.
•lactic acidosis with high
concentration of lactate and
pyruvate in CSF and blood
Biotin responsive encephalopathy
5 month MRI follow-up
Pharmacologic doses of biotin
normal pattern of the spectrum
from right caudate et putamen
and no lactate is detected
Progression of myelination with resolution of WM and GM abnormalities except for the genu of
the corpus callosum which remains in high signal T2, low signal T1 and high ADC level, stigmate
of cystic degeneration.
Childhood WM Disorders and MR parametric
approach
• Prospective Study (1) of 41 patients with WM disorders of
known cause :
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12 hypomyelinating,
14 Demyelinating (10 Metachromatic and 4 Krabb),
5 disorders with myelin vacuolation
10 disorders with cystic degeneration
• Using MR parameters : MTR, ADC, FA and MRS
• Discrimination between different types of pathologic
conditions thar underlie signal intensity abnormatities in
the WM
• Linear discimination analysis showed
– The combination of tCr, Cho, MTR and ADC mesurements results in only 2
misclassification
– 95 % of patients were correctly classified.
(1) Van der Voorn JP et al , Radiology 2006; 241 : 510.
T2WI
ADC
FA
MTR
MRS
Healthy 5-year-old boy
2-year-old boy with
hypomyelination
6-year-old boy with
demyelination
11-year-old girl with
myelin vacuolation
3-year-old girl with
cystic degeneration
Oumaima, 8 years-old. Fever, Sudden onset Upper Limbs paresthesia
Treated as viral encephalitis
CT Day 7
MRI Day 8
3 Weeks later: Fever, headache and seizures. Cerebellar ataxia,
facial and brachial motor deficit
4 months
Acute disseminated Encephalomyelitis ADEM
– CNS demyelinating disease more frequently diagnosed (1) : 0,4 /
100000/year with incidence quadruple (98 – 2000 v/s 91-98) >>>
MRI and Flair in acute encephalopathy
– Usually following benign infection or vaccination in healthy young
person
– Acute neurologic symptoms with imaging evidence of
demyelination: MRI required, CT usually normal.
– Dilemna >> distinguish ADEM from MS: 4/42 (9.5%) initially
diagnosed with ADEM were MS cases after episodes of
demyelination (1).
(1) Leake JA et al Pediatr Infect Dis J 2004, 23 : 756.
ADEM
• Clinical impairement faster
than neuroradiological
deterioration
• Usually complete regression
of clinical and neuroradiological
symptoms
• Remaining deficit 10 – 20 %
J4
1 Week Later
3 Weeks Later
ADEM
Heterogenous disease with variable course and development
– Monophasic form
– RDEM : Relapses with sterotype symptoms and without new MRI lesions
– MDEM : reccurent pattern in long lengths of time (years) with new
symptoms and corresponding new MRI lesions
– AHEM : rare, hyperacute onset , monophasic course with fever and severe
neurologic dysfunction. Fulminant and often mortel outcome.
Spectrum of pathologies still imprecisely known
Most important pronostic factor for differential diagnosis with MS :
FOLLOW-UP
ADEM Differential diagnosis
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Lyme’s disease
Subacute Sclerosing Panencephalitis
Progressive multifocal leucoencephalopathy
Blood coagualtion diseases
Vasculitis
Leucodystrophies
Mitochondrial diseases
Haematologie disorders
Optic neuromyelitis – subform of ADEM
Schilder and Balo diseases (variant of MS)
MS ++
5Y
11 Y
Blindness
and
paraplegia
Pediatric MS
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4 reviews concerning MS in childhood and summarizing
published literature between 2005 – 2007.
2 Focusing on MRI features
All reviews state that children
• are more likely to have monosymptomatic illness
• Have typically fewer lesions than adults
• with lower propensity for lesions to enhance with gadolinium.
(1) Banwell B et al Neurology 2007; 68: 546
(2) Chabas D et al NeuroRX 2006; 3: 264
(3) Pena JA et al Invest Clin 2006; 47: 413
(4) Waldman A et al Ment Retard Dev Disabil Res Rev 2006; 12: 147
3 years-old, right hemiparesis with rapidly progressive onset
IRM J8
Extensive WM hypodensities : relapse
immediatly after TTT arrest
Corticotherapy: complete regression
of the symptoms and considerable
decrease in cerebral lesion
IRM at 6 years
Sequellea: R hemiparesis
Pediatric MS
• MRI criteria specific for pediatric onset MS and
criteria predictive of MS outcome in children
with first demyelinating event : challenged by the
over lap in MRI features between MS and ADEM
• Most important differentiel criteria : Follow-up.
Pediatric MS
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13 Y
Rare in childhood : less than 1 %
of MS cases begin in the first
decade (1)
Symptoms usually less severe
MRI lesions multiple
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Mainly in periventricular areas
Middle cerebellar peduncle
Sharper margins
Small with variable enhancement : Active
lesion coexisting with silent lesions
Tumefaction lesions > 20 mm.
(1) Dale RC et al, Brain 2000; 123 : 2047
5Y
Pediatric MS
• demonstrate several differences
– Initial presentation : frequently simulates ADEM or acute
metabolic encephalopathy.
– 5 : 1 female predominance in adolescence v/s 1.4 to 1.9 : 1 in
adults
– Cerebellar and brainstem plaques more frequent : 70 – 80 %
– Tumoral form : even if uncommon, mostly seen in children. Size
and enhancement >>> DD with abscess and tumor. MRS :
indistinguishable from tumor spectra.
• Incomplete rim enhancement and mild edema and mass effect.
10 years-old boy with intense headache and 01 week before:seizures
CT 2 years
later
Resolutive multiple relapses: visual loss, seizures, paraparesis
Sudden visual loss
Follow-up MRI
5 years later
17-year-old female, with tetraplegia , ataxia and urinary disturbance.
•Balo’s concentric sclerosis (BCS)
•Rare demyelinating disease: Balo in 1928 (post mortem)
•variant of MS
•typical concentric mass patterns on MRI
•characteristic alternating rings of demyelination
and spared myelin
Glomerulonephritis
CRF . Seizures and coma. Hypertension
Severe GNA hemodialysis
Posterior Reversible Encephalopathy
syndrom: PRES
• Relatively new clinical• 20 cases, most with severe
radiological entity : 1996 in
alterations in consciousness and
adults with renal insufficiency,
seizures
hypertension, immunosuppression
• Usually benign and reversible
• Age 1.9 to 18.3 years
• 10 (177) kidney transplant
• Hypertension and Calcineurin
recipients: 6 cyclosporine and 4
inhibitor administration: chief
Tacrolimus
risk factors. Characteristics of
PRES in pediatric patients remain • 5 (87) nephrotic syndrome
(cyclosporine)
obscure.
• AWARENESS of this syndrome • 5 acute post streptococcal
glomerulonephritis, diffuse
possibly traitable
mesangial sclerosis…
• Clinically :
– Generalized TC seizures: 60 %
Ishikura K et al, AJ Kidney disesases 2006, 48 : 235
– Hypertensive crises: 60 %
PRES in children
• Diagnosis improved with MRI – Flair > CT
Combination MRI – CT recommanded
• Abnormalities : edema in posterior WM regions, bilateral in
parieto-occipital
• 17/20 abnormalities (1) extented
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GM
Frontal and temporal
cerebellum (16/20).
Lower ADC value indicate cystotoxic edema with ischemic infarct
• Differential diagnosis:
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Ischemic stroke
Cerebral venous thrombosis
Vascularitis
Progressive multifocal leucoencephalopathy
Adrenaleucodystrohy…
(1) Ishikura K et al, AJ Kidney disesases 2006, 48 : 235
PRES in children
• Key points
– Should be suspected with any sudden episode of
neuroradiological symptoms in patients with Kidney diseases
– Should be considered event when imaging findings are not
restricted to subcortical WM in parieto occipital regions
– Significant effect of early management on prognosis :
rigourous and meticulous control of BP is Mandatory
(antihypertensive therapy, hemodialysis). Reversible is
inaccurate >>> Importance of DWI for differentiation
cytotoxic v/s non cytotoxic edema.
10-year-old girl with ALL who presented with
posterior headaches and seizures
CNS Manifestations in 49 Patients with
Oncohematologic Disease
CNS Manifestation
No. Of Patients
Manifestations of primary disease
(n 11)
Hemorrhage 1
CNS involvement
Meningeal infiltration 2
Parenchymal infiltration 1
Bone marrow infiltration 2
Orbital infiltration 3
Spinal infiltration 2
Effects of therapeutic methods
38)
Reversible posterior leukoencephalopathy
Dural Venous Thrombosis
(n
Effects of radiation therapy
White matter disease 3
Mineralizing microangiopathy 3
Parenchymal volume loss 12
Radiation-induced cryptic
Malformations 2
Second neoplasms 2
Effects of chemotherapy and bone
marrow transplantation
Hemorrhage 3
Dural venous thrombosis 3
White matter disease 2
Reversible posterior encephalopathy 4
Effects of immunosuppressive states
Infectious processes 4
V’azquez E et al, RadioGraphics 2002; 22:1411–1428
Phacomatosis NF1
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Hyperintense lesions are highly prevalent and
characteristic in patients with NF1
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MRI contributed to a definitive diagnosis of
NF1 in 53 % of suspected cases
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Follow up studies are necessary in the
evaluation of suspected NF1 even if the 1st
examination is negative (1,2)
(1) Menor F e al, Eur J Radiol 1998, 26 : 121
(2) Balestri P, Child Nerr syst 1993, 9 : 448
Phacomatosis
• Neurofibromatosis type1 NF1
– 72 NF1 in recent review with follow-up
(1)
– T2 high signal lesions UBOS dectected in :
• Basal ganglia, cerebellum
• Globus pallidus
– 45 follow up with 3 years mean interval
– WM lesions cerebellum and brainstem
• Decreased in size 40 %
• Involutional tendency occured in children
older > 10 years.
(1) Menor F e al, Eur J Radiol 1998, 26 : 121
WM lesions in TS :
• Noted in all cases
• Supratentorial localization.
• Most commonly:
– Isointense or hypointense to
normal WM on T1 SE
– Hyperintense on T2 SE and
FLAIR.
– Superiority of MT-T1WI over
Flair is demonstrated.
• MR pattern
• linear and radial
• nodular
• Cyst-like: 8/18 patients (1) iso
intense to CSF
(1) Van Tassel P et al, AJNR 1997 ; 18 : 1367
Conclusion
• MR Imaging highly sensitive in the detection of WM lesions
• Integrated description of clinical, neuroimaging and
pathophysiological features is crucial for categorizing myelin
disorders.
• MR, primary imaging modality in patients with leukodystrophy:
important role in the identification, localization, and
characterization of underlying WM abnormalities.
• MR serve to redefine and broaden the disease spectrum of
reported WM abnormalities in children
• Quantitative MR techniques : may HELP to CLASSIFY
unknown WM lesions in subgroups