2015 asnr aspnr interesting case session (1)

www.aspnr.org ASPNR@The _ASPNR
ASPNR
INTERESTING
CASE SESSION
2015
ASNR 53rd
ANNUAL
MEETING
April 25-30, 2015
Chicago, IL

Pediatrics case conference
ASPNR/ASNR 2015 Chicago
• Theme: Beat the Presidents

Case conference “designers”
Thierry A. Huisman and Andrea Poretti

• Theme: Beat the Presidents
• Participants:
– Presidents: Cally Robson and Dennis Shaw
– Challengers: Aylin Tekes and Asim Choudhri
– Helpers: The audience
– Referees: Thierry Huisman and Susan Palasis

Case 1 >>> Asim
• 9-month-old girl presenting with fever, cough
and rhinorrhea since 4 days
• Sudden onset of body stiffening, inability to
fixate or follow, right facial droop
• Previous Hx: born at 36 weeks

Brain MRI (same day at 02:00 pm)
T2w

T1 C+

Trace of diffusion
ADC

Brain MRA (same day at 02:00 pm)
3D TOF MRA

Neuroimaging findings
• Head CT (8:10 am):
– Poor definition of the deep gray nuclei without mass
effect
• Brain MRI (2:00 pm):
– Bilateral symmetric, patchy increased T2 signal and
mild swelling in the deep gray nuclei, periventricular
white matter, right precentral gyrus, dorsal
mesencephalon, and cerebellar white matter

• MRI (2:00 pm—continued)
– Mild T1 hypointensity in the region of T2 signal
abnormalities. ? Subtle contrast enhancement in the
region of T2/diffusion abnormalities, although pre-
contrast T1 weighted images are not available. No
leptomeningeal enhancement!
– Patchy restricted diffusion in the above mentioned
areas plus mesial temporal lobes.
• MRA (2:00 pm)
– Mild irregularity of the MCA distal branches (M2 and
M3)

Differential Diagnosis
• Bacterial meningitis with vasospasm
• Venous sinus thrombosis
• Acute Necrotizing Encephalitis
• Wernicke’s encephalopathy
• Demyelinating disease (ADEM)

Differential – Meningitis with vasospasm
• Signal abnormality typically
either along surface of brain,
or related to vasospasm
• Vasospasm will not typically
be symmetric

Differential – Meningitis with vasospasm
• Signal abnormality typically
either along surface of brain,
or related to vasospasm
• Vasospasm will not typically
be symmetric
• Symmetric findings and
involvement of brainstem
favor against this diagnosis

Differential – Venous thrombosis
• Deep venous thrombosis can
lead to central areas of venous
congestion/venous infarctions
in medial thalami
• T2 flow voids in internal
cerebral veins and vein of
Galen favor agianst this
• Brainstem involvement in
unknown case more than
typically seen in venous
thrombosis

Differential – Wernicke’s
encephalopathy
• Medial thalamic, peri-
aqueductal gray and
mamillary body abnormalities
• Duration of symptom onset
and supratentorial findings in
unknown case does not fit
with Wernicke’s
• No stated risk factor for
thiamine deficiency

Differential – ADEM
• Involvement of white matter
(including brainstem) and
heavily myelinated gray
matter areas (in particular
thalami)
• Typically no significant
diffusion restriction

Differential – Acute necrotizing
encephalitis
• Bilateral thalamic and
tegmental involvement
• Relative cortical sparing
• Diffusion abnormalities
• Acute onset
• Fits with unknown case!

Asim’s differential diagnosis
1. Bacterial meningitis with vasospasm
2. Venous sinus thrombosis
3. Acute Necrotizing Encephalitis
4. Wernicke’s encephalopathy
5. Demyelinating disease (ADEM)

Asim’s final diagnosis
• Acute Necrotizing Encephalitis

Correct answer
• Acute necrotising encephalitis (ANE)
• Brain teaser: Identification
of the disorder at the time
of neuroimaging study is
the most important
determinant of outcome
Okumura A et al, Brain Dev, 2009

Case 2 >>> Dennis
• 15-month-old boy with intractable seizures
despite several antiepileptic drugs, global
developmental delay, and gastroesophageal reflux
• Previous Hx: born at 35 weeks of gestation
• Laboratory: slightly low vitamin D level in blood
• Genetic analysis: small deletion on chromosome
2q32.1
• MRI one year before: mild global cerebral volume
loss

MRI
• Bilateral symmetric GP (not striatum), Thalamus,
pontine tegmentum/CTT
-T2 prolongation
-diffusion restriction
• Delayed myelination
• Inc extra-axial CSF (no cysts, cerebellar folia nl)
• BG/Thalamic/BS findings new: not reported on
MRI at 3 months

Bilateral symmetric GP: increased T2
• Symmetric: (metabolic/ immunologic pattern )
• Selective vulnerability GP (metabolic/immunologic)
• Metabolic
-Respiratory chain: Toxicity (CO), Mitochondrial dis.
-Other metabolic inborn errors: SSADH, MMA, GA
• Injury/stress: HII, Venous thrombosis, hypoglycemia,
osmotic demyelination, chronic kernicterus (born
@35wks)
• Immunologic: ADEM

Bilateral symmetric GP: increased T2,
with Diffusion Restriction
• Cytotoxic edema (vs vaculolating myelopathy)
• Acute phase:
-Respiratory chain: Toxicity (CO), Mitochondrial dis.
-Other metabolic in born errors: MMA, SSADH, GA
• [not kernicterus ]

Methylmalonic acidemia (MMA)
GP diffusion restriction
Michels; Ped Rad 2004

Methylmalonic acidemia (MMA)
• Heterogeneous group of AR metabolic disorders
• Inability to convert methylmalonate-CoA to
succinyl-CoA
• Characteristic: acute metabolic decompensation
• Characteristic: pallidum (occ w/o crisis reported)
• Delayed myelination/sulcation
• Tegmental, cerebellar lesions also reported
• [No reported thalamic involvement]

GA-I: GP diffusion restriction

GA-I: imaging
• GCDH (glutaryl-CoA dehydrogenase)
mitochondrial matrix enzyme involved in
degrading lysine, hydroxylysine , tryptophan
• Inc SA spaces/cysts: ant temp, sylvian [bat wing].
• Macrocephaly common
• Cerebral WM abn/ Delayed myelination.
• Striatum, GP, Thal, Sub Nigra, Dentate Nuc, CTT.
• Findings often develop encephalopathic crisis
(usual occurring 6-18 months).
• (GP injury can be seen w/o such episode).

Mitochondrial Disease: 1 y.o.- Intractable epil. DD:
Abnormal complex IV function- nuclear defect

Leigh Syndrome with COX Deficiency and SURF1
Gene Mutations: MR Imaging Findings
Rossi et al: AJNR 2003

Leigh Synd. SURF1 COX-
Savioardo; Ann. Neurology 2001
• 8 pts LS SURF1 associated with COX (complex 4)
deficiency
• All had lesions at different levels of the brainstem
(medulla, pontine tegmentum, periaqueductal)
• All symmetrical lesions in subthalamic nuclei.

53 week old with infantile spasms:
Vigabatrin

Vigabatrin
• Irreversibly inhibits GABA transaminase =>
inhibits catabolism of GABA .
• Also inhibits (ABAT) an enzyme that converts
dNDP to dNTP in the mitochondrial nucleoside
salvage pathway => mitochondrial depletion.

Dennis’ differential diagnosis
1. Methylmalonic acidemia (MMA)
2. Glutaric aciduria type I
3. Mitochondrial disorder
4. Vigabatrin induced

Dennis final diagnosis
• Vigabatrin (Mitochondrial)

Correct answer:
• Magnetic resonance imaging abnormalities
associated with vigabatrin
• Brain teaser: In a child with medication, think
always about medication neurotoxicity
Guleria S et al, Neurographics, 2012

Case 3 >>> Aylin
• 8-year-old girl with developmental delay, ataxia,
and teeth abnormalities
• Wearing glasses because of myopia; she also has
nystagmus
• Short toenails
• Previous Hx: born at 33 weeks as one of triplets

T2w
Small cerebellum with enlarged cerebellar fissures => cerebellar atrophy
↑ AP diameter of the globe due to myopia
Normal pituitary gland
T1w

T1w
↑ T1 and ↑T2 signal of the supratentorial white matter => hypomyelination
Dark spot on posterior limp of the internal capsule
Myelinated optic radiations
Normal basal ganglia
T2w

DD-list
1. 4H (Hypomyelination, Hypodontia and
Hypogonadotropic Hypogonadism)
2. H-ABC (Hypomyelination and Atrophy of the
Basal Ganglia and Cerebellum)
1. Gotta love diseases that are named after their imaging
findings!
3. Pelizaeus-Merzbacher disease (PMD)
4. Salla disease

Age 2y 8mo
Age 8y 2mo
Hypomyelination, cerebellar atrophy, basal ganglia atrophy
H-ABC
T2w
T2w
T1w
T1w

H-ABC
Pros
• Cerebellar atrophy
• Hypomyelination
• Developmental delay
Cons
• Basal ganglia atrophy
• Teeth abnormalities

Pelizaeus-Merzbacher disease
1 do
T2w
7 mo
Hypomyelination
T2w

Pros
• Hypomyelination
• Ataxia
• Nystagmus
Cons
• Normal cerebellar volume
• No dark spot on IC
Pelizaeus-Merzbacher disease

Salla Disease
Hypomyelination, rather normal cerebellum
T2w
T2w

Salla Disease
Pros
• Hypomyelination
Cons
• Rather normal cerebellum
• No dark spot in the IC

Aylin’s differential diagnosis
1. 4H (Hypomyelination, Hypodontia and
2. H-ABC (Hypomyelination and Atrophy of the
Basal Ganglia and Cerebellum)
1. Gotta love diseases that are named after their imaging
findings!
3. Pelizaeus-Merzbacher disease (PMD)
4. Salla disease

Aylin’s final diagnosis
4H (Hypomyelination, Hypodontia and

Correct answer
• Hypomyelination, hypodontia and hypogonado-
tropic hypogonadism (4H syndrome) due to
mutations in the POLR3A gene
• Brain teaser: The combination of neuroimaging
(hypomyelination and cerebellar atrophy) and
clinical (hypodontia) findings is often the clue for
a correct diagnosis

Case 4 >>> Cally
• 15-month-old girl with global developmental delay
and epileptic seizures
• No craniofacial dysmorphic features
• Increased patellar tendon reflex bilaterally
• Family Hx: 7-year-old brother with benign
Rolandic epilepsy

Summary of findings
• Pontine hypoplasia and clefting
• Abnormal pontine DTI
• Cerebellar malformation
• Inferior vermian hypoplasia
• Thinned corpus callosum
• Absent/hypoplastic anterior commissure
• Dysmorphic basal ganglia
• Asymmetric cortical malformation
• Hippocampal dysmorphism

Differential diagnosis
Pontine malformation
• Horizontal gaze palsy and progressive scoliosis (HGPPS)
– ROBO3 mutation (axonal guidance defect)
• Pontine tegmental cap dysplasia (PTCD)
– Axonal guidance defect
• Tubulinopathy
– TUBA1A mutation

Tubulinopathies
• Tubulin genes encode for tubulin proteins
• Tubulin proteins form the microtubule
cytoskeleton
• Essential in all stage of brain development
neuronal differentiation, migration & axon
guidance & maintenance

Phenotypic spectrum of tubulin-
related disorders
• TUBA1A
• TUBA8
• TUBB2B
• TUBB3
Cortical malformations
Defects in commisural fiber tracts
Degeneration of motor and sensory axons
Basal ganglia dysmorphisms

Description of a novel TUBAlA mutation in Arg-390
associated with asymmetrical polymicrogyria and
mid-hindbrain dysgenesis
Ginevra Zannia, Giovanna S. Colafatib, Sabina Barresi a,
Francesco Randisi b, Lorenzo Figa Talamanca b, Elisabetta Genovesec,
Emanuele Bellacchiod, Andrea Bartuli e, Bruno Bernardi b, Enrico Bertinia,•

Table 1
Summ ary of the phenotypic spec1rum of the tub ulin-related d isorders.
LIS = llssencephaly; MCD mallormations or cortical developm e n PMG = polymicrogyria:CFEOM3 = congenllal fibrosis orthe extraocular m uscle
type 3.
Current Opinionin Genetics & Development 2011, 21:28lh294
Tubulln lsotype TUBAlA TUBB2B TUBB3 (a) TUBB3 (b)
Number or reported mutations 25 Missense Five missense Six mlssense 8ght mlssense
Phenotyplc spectrum
Clinical disorder Severe LIS to MCD PMG MCD Axon guidance
disorder,CFEOM3
nte ectualand social Genera y severe Generaly severe Mild to severe Normalto rroderale,
disablty mutation dependent
Head clrcumlerence Most mlcrocephalc Microcephalc
1<3-50"I Generally normal,
mutation dependent
Epilepsy Can be present Can be presert Canbe presert Absent
Strabisrrus Corn ant to absert Notindcated Corrltant Ir:> absent lncorritant (CFEOM3) to
rarely absent,
mutation dependent
Degenerative peripheral No No No Yes,mutation
neuropathy dependent
Felr:>psy and/or MRI nell"Oimaglng data
Published relopsy Yes Yes Yes No
Cortex Complete agyria Ir:> Biateral to assymetric Ussencephaly Ir:> Generally normal
mild gyral maWormation polymicrogyria gyraldisorganization
Major cortical location Diffuse,posterior, Frontal,parietal,and Perisylvlan to NA
perisylvian,or frontal temporal lobes rronloparletal
Corpus callosum Agenesls lo mild Agenesis to mild Agenesls to normal Agenesis to normal;
dysgenesis,probst dysgenesis probst bundles
bundles reported reported
Evidence or primary axon Possibly No Yes Yes
guidance defect
Basal ganglia appearance Dysmorphic to normal Dysmorphic to normal Dysmorphlc to normal Dysmorphlc to
normal
Cerebellum Vermis > generalized Vermis > generalized Vermls > generalized Mild dysplasia
hypoplasla,occasionally hypoplasia hypoplasla to normal
normal
Gross bralnstem Hypoplasla to normal Hypoplasia to normal Hypoplasla to normal Normal
appearance

Cally’s differential diagnosis
1. Horizontal gaze palsy and progressive scoliosis
(HGPPS)
ROBO3 mutation (axonal guidance defect)
2. Pontine tegmental cap dysplasia (PTCD)
Axonal guidance defect
3. Tubulinopathy
TUBA1A mutation

Cally’ s final
diagnosis
Tubulinopathy (TUBA1A mutation)

Correct answer
• Tubulinopathy due to TUBA1A mutation
• Brain teaser:
Amron D et al, Clin Genet, 2014

Case 5 >> Asim
• 2.5-year-old girl with global developmental delay
• Hyperopia and astigmatism
• No obvious craniofacial dysmorphic features
• Lead level in blood: 6 mcg/dL (normal <5)
• Previous Hx: ventriculomegaly on prenatal
ultrasound
• Family Hx: paternal uncle and cousin with
Duchenne's muscular dystrophy

• Midline continuity of posterior frontal lobes
– Continuity of gray and white matter
• Absent septum pellucidum
• Abnormal Sylvian fissures
• Normal deep gray nuclei, including diencephalic
structures (thalami, hypothalamus)
• Partial dysgenesis of the corpus callosum
– Body dysplastic/absent
– Genu, rostrum and splenium present

Differential Diagnosis
• Syntelencephaly
• Holoprosencephaly
• Schizencephaly
• Bilateral Perisylvian polymicrogyria

Differential - Holoprosencephaly
• Incomplete hemispheric
separation
– Holo = one
– Prosencephalon = forebrain

Differential - Holoprosencephaly
• Incomplete hemispheric
separation
– Holo = one
– Prosencephalon = forebrain
• Prosencephalon later
differentiates into
– Diencephalon (thalamus, etc)
– Telencephalon (cerebral
hemispheres)

Differential – Schizencephaly
• Schizencephaly = cleft
– Schism = separation
• Abnormal white matter, deep
sulci, and corpus callosum in
unknown case, but no visible
cleft

Differential – Perisylvian polymicrogyria
• Abnormal perisylvian region,
but no polymicrogyria in the
unknown case

Differential – Syntelencephaly
• Syn = together (as in synapse)
• Telencephalon =
prosencephalon (cerebral
hemispheres) without
diencephalon (thalami, etc)
• Vertically oriented sylvian
fissures
• Fits with unknown case!

Asim’s differential diagnosis
1. Syntelencephaly
2. Holoprosencephaly
3. Schizencephaly
4. Bilateral Perisylvian polymicrogyria

Asim’s final diagnosis
Syntelencephaly

Correct answer
• Syntelencephaly or middle interhemispheric
variant of holoprosencephaly
• Brain teaser: The corpus callosum does not
develop from the front to the back, but the
different components develop independently
and fuse at a later embryological stage

Case 6 >>> Dennis
• 9-year-old girl with progressive hearing and vision
impairment
• Microcephaly, short stature, and failure to thrive
• No dysmorphic feature, normal skin, intention
tremor
• Previous Hx: “flu-like” symptoms of the mother
during almost the entire second and third
trimester of her pregnancy, eosinophilic
esophagitis

ADC
Trace of diffusion
chilblain-like lesions

Summary of findings/history
• Basal Ganglia Ca+
• White matter disease
• Volume loss/Atrophy
• Normal MRA
• 9y F: FTT, short stature, microcephaly
• Progressive hearing, vision loss
• History of ‘flu like’ illness during pregnancy
• No skin lesions, not dysmorphic

Cerebral WM
abnormality/Leukodystrophy and
Basal Ganglia Ca++
• Congential infection: TORCH [CMV]
• Aicardi-Goutières syndrome (AGS)
• Cockayne syndrome (CS)

Congenital CMV:
• Intracranial Ca+ (34-70%)
• WM abn (≈20%)
• Cortical migration abn: PMG
• Atrophy/Microcephaly (≈¼)
• Cerebellar volume loss
• SNHL (Progressive 50%)
• Chorioretinitis, optic atrophy
• DD

Congenital CMV:
Periventricular Ca+ most common

Congenital CMV: Cortex
Cortical malformation: PMG

Congenital CMV: WM disease
-Variety of patterns: focal, patchy or confluent-
posterior and frontal predominate reported:.
-Delayed/dysmyelination, WM disease
[WM abn may be the only abnormality]

Congenital CMV: WM disease
• Cysts, anterior temporal
• Periventricular cysts are also
reported

Aicardi-Goutières syndrome – (TREX1)
GE

Aicardi-Goutières syndrome (AGS)
• Auto inflammatory disorder mimicking in
utero viral infection of the brain
• Chronic and inappropriate innate immune
response
• Autosomal recessive inheritance: 5 genes
identified to date

• Intracranial Ca+; Basal Ganglia, Peri/para
ventricular, Dentate Nuclei
• Leukodystrophy: esp frontal-temporal (temporal
cysts in some)
• Cerebral, cerebellar and brain stem atrophy
reported

• DD, FTT (20% present with neurologic abn at birth;
majority present later sub-acute encephalopathic
phase- then stable)
• Visual function: varies- normal to cortical blindness
• Hearing almost always normal
• Skin: chilblain-like lesions (40%)

9 year old: Cockayne Syndrome
Courtesy of Samantha Marin, MD

Cockayne Syndrome: clinical findings
• Mutations in CSA or CSB proteins; involved in
nucleotide excision repair (actively transcribing genes
targeted)
• 4 overlapping clinical subgroups (decreasing severity):
COFS, CS II, CS I, and CS III
• Microcephaly, FTT, short stature
• DD/ intellectual disability, progressive neurological
dysfunction
• Progressive SNHL and atypical retinitis pigmentosa
• [Cutaneous photosensitivity]

Neuroimaging In Cockayne Syndrome
Kooba et al AJNR 2010
• Reviewed 19 cases (2 COFS, 6 CS II, 8 CS I, 3 CS III)
• Basal ganglia Ca+ (16/18): putamen most common-
either isolated or with cortex, dentate, caudate,
pallidum, more rarely, the white matter, thalami
• WM disease (hypoattenuation 10/19) centrum
semiovale, periventricular; mainly frontal
• Atrophy (19/19) mild-severe: supratent correlated
with WM disease; brainstem, cerebellum- variable,
usually moderate-severe

• CMV [incidence 0.2% to 2.2% all live births; 8000
infants/year in US with CMV-related neurologic
deficits].
• Cockayne Syndrome [≈200 reported cases]

Dennis’ differential diagnosis
1. Congential infection: TORCH [CMV]
2. Aicardi-Goutières syndrome (AGS)
3. Cockayne syndrome (CS)

Dennis’ final diagnosis
Cockayne syndrome

Correct answer
• Cockayne syndrome due to homozygous
mutations in the ERCC8 gene
• Brain teaser: SWI is a gradient-echo MRI
sequence with a high sensitivity for blood, blood
products, nonheme iron, and calcifications within
the brain; it may be used instead of a CT  in
children think about ALARA!
Bosemani T et al, J Magn Reson Imaging, 2014

Case 7 >> Aylin
• 13-year-old male with progressive weakness and
difficulty to walk
• First symptoms started at the age of 2 years
• Frontal bossing, abnormal dentition, abnormal feet
• Global weakness (legs>arms), weak tendon reflexes
• Previous Hx: ectodermal dysplasia
• Family Hx: mother had breast cancer

T2w T1 C+ T2w
Diffuse uniform thickening/hypertrophy and contrast enhancement of the
cauda equina nerve roots filling the thecal sac

Diffuse uniform thickening/hypertrophy and contrast enhancement of the
exiting cervical nerve roots and occipital nerves.
(-) leptomeningeal enhancement
Cyst in the right sphenoid wing, ? incidental
T2w T2w T1 C+

DD-list
1. Guillan Barre/CIPD
2. Charcot-Marie-Tooth
(Hereditary Motor and Sensory Neuropathy)
3. Leptomeningeal carcinomatosis
4. Lyme disease

Guillan Barre/CIDP
T2w T1 C+ T2w
T1 C+
T1 C+
Smooth mild thickening and enhancement of the cauda equina
Leptomeningeal enhancement
Cranial nerve (V) enhancement

Guillan Barre/CIDP
Pros
• Nerve thickening and
enhancement
Cons
• Cranial nerve involvement
• Leptomeningeal
enhancement
• Acute onset
– Ascending paralysis which typically
improves
• Abnormal dentition
• Abnormal feet

Leptomeningeal Carcinomatosis
T2w T1 C+ T2w
T1 C+
T1 C+
Irregular thickening/clumping and enhancement of the cauda equina nerve roots.
Leptomeningeal thickening and enhancement
Pineoblastoma

Leptomeningeal Carcinomatosis
Pros
enhancement
Cons
• Irregular nerve
thickening/clumping
• Leptomeningeal
enhancement
• Pineal tumor
• Abnormal feet

Lyme Disease
T2w T1 C+
T2w
T1 C+
T1 C+
Smooth mild thickening and enhancement of the cauda equina
Cranial nerve (V, VII, VIII) enhancement

Lyme Disease
Pros
enhancement
Cons
• Smooth, mild thickening
and enhancement of the
cauda equina
• Cranial nerve (V, VII, VIII)
enhancement
• Abnormal feet

Aylin’s differential diagnosis
1. Guillan Barre/CIPD
2. Charcot-Marie-Tooth
3. Leptomeningeal carcinomatosis
4. Lyme disease

Aylin’s final diagnosis
Charcot-Marie-Tooth

Correct answer
• Charcot-Marie-Tooth disease (genetically proven)
• Brain teaser: Multiple nerves involved, multiple
physicians involved

Case 8 >>> Cally
• 2-year-old male with therapy refractory seizures
and global developmental delay
• Disconjugate eye movements, weakness of the
right arm compared to left arm
• Linear areas of hyperpigmentation on the neck
and right arm, large areas of alopecia
• Previous Hx: infantile spasms and placement of a
gastrostomy tube
• Family Hx: 12-year-old sister with NF1

Findings
• Multiple lipomas
– Frontotemporal
– Scalp: ? Nevus psiloliparus
– Intraspinal
• Cerebral asymmetry
• Prominent PF CSF space & cerebellar asymmetry
• Abnormal WM signal Lt frontal ? Lt temporal

Differential diagnosis
• Encephalocraniocutaneous lipomatosis (Haberland
syndrome) (ECCL)
• Oculoectodermal syndrome (? ECCL variant)
• Oculocerebrocutaneous (Delleman) syndrome
• PHACES
• Proteus syndrome (AKT1)
• PIK3CA-related overgrowth spectrum
– CLOVES syndrome
– Fibroadipose hyperplasia/overgrowth
– Hemihyperplasia multiple lipomatosis
– Megalencephaly syndromes

Pl3K-AKT Signaling Pathway
PIP3 PDK1
P13 l
AKT
I Thr308
..........
P/K3CA-Related
Overgrowth Spectrum
(PROS)
• Macrodactyty
• Hemihyperplasia
Multiple Lipomatosis (HHML)
• Fibroadipose overgrowth (FAO)
• Muscle Hemihypertrophy
• Facial lnfilitrating Lipomatosis
· CLOVES
•Megalencephaly -
Capillary Malformation (MCAP)
• Skin disorders:
Epidermal nevi,
Seborrheic keratoses,
Benign lichenoid keratoses
PIP3 · Proteus Syndrome (AKT1)
• Lipodystrophy syndrome - Hypoglycemia (AKT2)
· Hemimegalencephaly and
Megalencephaly-polymicrosyria-
polydactyly-hydrocephalus (MPPH) (AKT3)i Ser473t
mTOR2 mTOR1
Bannayan - Riley - Ruvalcaba
and Cowden and Type II
Segmental Cowden syndrome
Lhermitte-Duclos disease
mTOR r .J( T' _ /
j ( !SC! } (TSCVl t
" '
• Hemimegalencephaly
Cell cycle/apoptosis regulation, metabolism, angiogenesis

Proteus
• Cerebriform connective tissue nevus
• Epidermal nevus
• Calvarial hyperostosis
• Dysregulation of adipose
– Lipoma
– Lipohypoplasia
– Fatty overgrowth
– Localized fat deposits/partial lipohyperplasia
• Vascular malformations

CLOVE Syndrome
Congenital Lipomatous nevi
Overgrowth
Vascular malformations
Epidermal nevi

Epidermal nevus syndrome
• Epidermal nevi following lines of Blaschko
• Choristoma, coloboma
• Hemimegalencephaly
• Gyral malformations
• Porencaphaly, Ca++
• Intracranial & intraspinal lipomas

ECCL
• Focal alopecia
• Nevus psiloliparus
• Frontotemporal/zygomatic lipomas
• Orbital choristoma, ocular anomalies
• Cicatricial upper eyelid retraction
• Café au lait spots or hyperpigmentation
• Porencephaly, unilateral VM, atrophy
• Arachnoid cysts
• CNS lipomas, Ca++
• Abnormal leptomeningeal vessels
• Jaw tumors, lytic bone lesions

Cally’s differential diagnosis
1. Encephalocraniocutaneous lipomatosis (Haberland
syndrome) (ECCL)
2. Oculocerebrocutaneous (Delleman) syndrome
3. PHACES
4. Proteus syndrome (AKT1)
5. CLOVES syndrome

Correct diagnosis
• Encephalocraniocutaneous lipomatosis
• Brain teaser: The combination of cerebral and
spinal neuroimaging findings may be the clue for
a correct diagnosis

2015 asnr aspnr interesting case session (1)

Recommended

Recommended

More Related Content

Recently uploaded

Recently uploaded (20)

Featured

Featured (20)

2015 asnr aspnr interesting case session (1)