Pathologies de la substance blanche chez

l’enfant

Dr. Kalthoum TLILI-GRAIESSMaster 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.

• 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…

Children WM Disorders

Genetic WM Disorders

• Well defined leucoencephalopathies – 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.

• Characteristic MR pattern : Metachromatic leucodystrohy, ALDX, Canavan disorder…

• Role of MR techniques in the discrimination of differents WM disorders: Parametic imaging.

Genetic WM Disorders

Classic: Sparing of the subcortical U fibersand periventricular WM. Tigroid patternFrequent involvement: CC,IC, corticospinaltracts

Metachromatic leukodystrophyKrabbe disease

Early-onset form: pyramidal tract, periventricular WM, cerebellar WM,and deep gray matter ,The most often affected

Adrenoleucodystrophy, X linked ALD

(1) Cheon JE et al, Radiographics 2002;22:461

Symmetric abnormal signal internal capsule, deep cerebelar WM and descending pyramidal tract

Symmetric WM demyelination in peri-trigonal regions Extendion across the corpus callosum spleniumSpread outward and cephalad

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 lesionsVariable basal ganglia involvementTypical 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

Megalencephaly-leucoencephalopathy with sub cortical cysts

Mutation MLC1 gene although variable phenotype

Cerebral WM involvement in Mitochondrial disorders

• Major findings : Alteration of basal ganglia and Brainstem

• Demonstrated that severe WM involvement is possible (1,2) and even the only abnormal neurologic features (3) : 3 unrelated families / 5

• Suggestive findings of mitochondria disease :– 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

13 months-old. Complexe II deficiency

Leigh disease

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

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.

normal pattern of the spectrum from right caudate et putamen and no lactate is detected

Childhood WM Disorders and MR parametric approach

• Prospective Study (1) of 41 patients with WM disorders of known cause : – 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.

Healthy 5-year-old boy

ADCT2WI FA MTR MRS

2-year-old boy with hypomyelination

3-year-old girl with cystic degeneration

6-year-old boy with demyelination

11-year-old girl with myelin vacuolation

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 knownMost important pronostic factor for differential diagnosis with

MS : FOLLOW-UP

ADEM Differential diagnosis

– 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 ++

5 Y

11 Y

Blindness and paraplegia

Pediatric MS

– 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

IRM J8

Extensive WM hypodensities :

relapse immediatly after TTT arrest

3 years-old, right hemiparesis with rapidly progressive onset

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.

– Rare in childhood : less than 1 % of MS cases begin in the first decade (1)

– Symptoms usually less severe– MRI lesions multiple

• 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

Pediatric MS 13 Y

5 Y

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

Sudden visual loss

CT 2 years later

Follow-up MRI 5 years later

Resolutive multiple relapses: visual loss, seizures, paraparesis

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-radiological entity : 1996 in adults with renal insufficiency, hypertension, immunosuppression

• Usually benign and reversible

• Hypertension and Calcineurin inhibitor administration: chief risk factors. Characteristics of PRES in pediatric patients remain obscure.

• AWARENESS of this syndrome possibly traitable

• Clinically : – Generalized TC seizures: 60 %– Hypertensive crises: 60 %

• 20 cases, most with severe alterations in consciousness and seizures

• Age 1.9 to 18.3 years

• 10 (177) kidney transplant recipients: 6 cyclosporine and 4 Tacrolimus

• 5 (87) nephrotic syndrome (cyclosporine)

• 5 acute post streptococcal glomerulonephritis, diffuse mesangial sclerosis…

Ishikura K et al, AJ Kidney disesases 2006, 48 : 235

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 – GM – Frontal and temporal– cerebellum (16/20).– Lower ADC value indicate cystotoxic edema with ischemic infarct

• Differential diagnosis:– 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

Reversible posterior leukoencephalopathy

Dural Venous Thrombosis

CNS Manifestations in 49 Patients withOncohematologic DiseaseCNS Manifestation No. Of Patients

Manifestations of primary disease (n 11)

Hemorrhage 1CNS involvement

Meningeal infiltration 2Parenchymal infiltration 1Bone marrow infiltration 2Orbital infiltration 3Spinal infiltration 2

Effects of therapeutic methods (n 38)

Effects of radiation therapyWhite matter disease 3Mineralizing microangiopathy 3Parenchymal volume loss 12Radiation-induced crypticMalformations 2Second neoplasms 2

Effects of chemotherapy and bonemarrow transplantation

Hemorrhage 3Dural venous thrombosis 3White matter disease 2Reversible posterior encephalopathy 4

Effects of immunosuppressive statesInfectious processes 4V’azquez E et al, RadioGraphics 2002; 22:1411–1428

• Hyperintense lesions are highly prevalent and characteristic in patients with NF1

• MRI contributed to a definitive diagnosis of NF1 in 53 % of suspected cases

• 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 NF1

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

• 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

ConclusionConclusion