ASPNR Interesting Case Session

Case 1

Dr. Kling Chong

Team Gray Matter

Case 1

• 13 month old girl

• 4 day history of vomiting and fever

• Status epilepticus

Case 1 (Day of Admission)

Case 1 (Day of Admission)

PCASL Rel CBF

Case 1 (21 days later)

Findings

• Day of admission:

– GM and WM are involved;

– Hyperintensity on T2 and restricted diffusion involving left

temporal lobe and thalamus - pulvinar (due to seizure?) and

ventromedial

– Leptomeningeal enhancement

– MRA: hyperemia / engorgement

– SWI: Paucity of deoxyhemoglobin in veins on involved side –

less O2 extraction or compression?

Globular focus of susceptibility – artifactual?

– ASL CBF - increased

Findings

• Follow-up (21 days):

– Atrophy in cortex and WM of involved regions, and to a

lesser extent of the deep grey WM

– Marked rarefaction of the subcortical white matter

A. Hypoglycemia

B. Thrombo-embolic infarction

C. Herpes Simplex infection

D. MELAS

E. Hypoxic-ischemic brain injury

What is your diagnosis?

Differential “ - Hypoglycemia

15 month-old girl presenting with seizures

Congenital adrenal hyperplasia

Acute Brain Injury in Hypoglycemia

Chronic Brain Injury from

Hypoglycemia

9 year-old girl with history of insulinoma s/p resection, now with first time seizure

Differential ” - Thrombo-embolic

infarction

30 month old girl with right hemiplegia for 3 days

Sickle Cell Disease; acute, subacute and chronic arterial ischemic stroke

Chronic Injury from infarction

Meningitis with venous infarcts

Differential C – Herpes simplex infection

10 year old girl - H Simplex encephalitis; HSV by DNA in CSF on PCR

11 yo HSV

Differential D - MELAS

7 y.o. - Recent seizures, transient visual symptoms

Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes

Differential E – Hypoxic-ischemic

brain injury

12 month old girl - Cardiac arrest during induction for cardiac surgery;

23 mins down time; MRI day 5

HIE – Day 2 of life

Final Diagnosis

Herpes Simplex

Infection

HIE – @ 4 weeks 1 month old; premature 36 week;

parechovirus infection with cardiovascular collapse @ 4 weeks

Age 4 weeks Age 4 years

A. Hypoglycemia

B. Thrombo-embolic infarction

C. Herpes Simplex infection

D. MELAS

E. Hypoxic-ischemic brain injury

What is your diagnosis?

C. Herpes Simplex infection

Correct Diagnosis

Case 2

Dr. Arastoo Vossough

Team White Matter

• 21-month-old girl

• Acute, progressive strabismus

• N.E: muscle hypotonia, brisk tendon reflexes,

supported walking, ataxia

• Lab: transaminases, γGT

Case 2 (At Presentation) Provided by Andrea Rossi

MRI at 21 months

• 22 months: irritability, gait difficulties following acute

upper airway infection

• 26 months: strabismus, irritability, muscle hypotonia

and weakness with reduced tendon reflexes,

supported footdrop gait

• CSF: increased protein with normal cell count

Case 2 (Continued)

MRI at 26 months

• Intravenous immunoglobulin treatment with little

benefit

• 3 years: seizures, dysphagia, difficult speech, mental

deterioration, severe muscle hypotonia and weakness,

inability to stand and walk

Case 2 (Continued)

MRI at 36 months

Brain MRI at 36 months

What is your diagnosis? A. Charcot-Marie-Tooth disease

B. Guillain-Barrè (Miller –Fisher) syndrome

C. Lyme disease

D. Metachromatic leukodystrophy

E. Krabbe Disease

Findings

• MRI at 21 Months:

– Normal MRI (T2, FLAIR, diffusion)

– Normal MRS

• MRI at 26 Months:

– Cauda equina nerve root enhancement

• MRI at 36 Months:

– Cauda equina and cranial nerve root enhancement

– Cranial nerve root enhancement (CNV + CNVII-VIII)

– White matter signal abnormality with “tigroid” pattern and patchy areas of restricted diffusion

Charcot-Marie-Tooth Disease

Hereditary motor-sensory neuropathy (HMSN)

Heterogeneous group of clinically (9) and

genetically (~50) categorized disorders

One of most common inherited neurologic

diseases

AD, AR, X-linked types

T1WI C+: Enlargement and often enhancement

of nerves

Peripheral nerves ± intradural nerve roots

Distal extremity atrophy

Charcot-Marie-Tooth Disease

X-linked subtype can have

brain signal abnormalities

White matter T2

hyperintensities and restricted

diffusion

Guillain-Barrè Syndrome • Commonly an acute inflammatory demyelinating polyneuropathy (AIDP)

• Autoimmune process - often preceded by an infection and viral illness

• Primarily a clinical diagnosis

• Features required for diagnosis

– Progressive weakness in both arms and legs (might start with legs)

– Areflexia (or decreased tendon reflexes)

• Features that support diagnosis

– Progression over days to 4 weeks

– Relative symmetry of symptoms

– Mild sensory symptoms or signs

– Cranial nerve involvement

– Autonomic dysfunction

– Pain (often present)

– High concentration of protein in CSF

– Typical electrodiagnostic features

Miller Fisher variant of

Guillain-Barrè Syndrome

Rare variant of Guillain-Barre syndrome (<5% of cases)

Characterized by ataxia, areflexia, and ophthalamoplegia

Descending symptoms

Antiganglioside antibody (Anti-GQ1b) in 90%

Most common MRI finding is a normal MRI

May have enhancing nerves

Patchy T2 signal abnormalities and posterior column

abnormalities reported

Miller Fisher. An Unusual Variant of Acute Idiopathic Polyneuritis

(Syndrome of Ophthalmoplegia, Ataxia and Areflexia). N Engl J Med

1956; 255:57-65

Charles Miller Fisher (1913-2012)

Father of modern stroke neurology

First dedicated stroke service, at MGH

Contributions: Carotid disease and stroke

Atrial fibrillation and stroke

Use of aspirin and anticoagulants

Transient ischemic attacks (TIA)

Characterization of carotid and vertebral arterial

dissection and relationship to stroke

Lacunar infarcts

SAH and aneurysms – Fisher grading on CT

Metachromatic Leukodystrophy

Leukodystrophy due to arylsulfatase A deficiency

Confluent, "butterfly-shaped" central cerebral

hemispheric T2 hyperintensity

Relative sparing in perivenular areas (Tigroid

pattern)

Early sparing of subcortical U-fibers

Can have enhancement of the cranial nerves

Can have enhancement of the spinal nerve roots

Metachromatic Leukodystrophy Enhancement of the cranial nerves Enhancement of the spinal nerve roots

Lyme s Disease

• Tick-borne multisystem inflammatory

disease due to Borrelia species

• Rash, arthritis, eyes, nervous system

• 10-15% develop neuroborreliosis

• Imaging:

– White matter lesions (may enhance)

– Multiple enhancing cranial nerves (CN VII most

common)

– Meningeal enhancement

– Cauda equina enhancement

Lyme s Disease

Neuroborreliosis

Imaging: White matter lesions (may enhance)

Multiple enhancing cranial nerves

(CN VII most common)

Meningeal enhancement

Cauda equina enhancement

Krabbe Disease

Leukodystrophy caused galactocerebroside ß-

galactosidase deficiency

Irritability and depressed deep tendon reflexes

Faint hyperdensity in thalami

Patchy T2 hyperintensity in deep, periventricular

WM and cerebellum

Can have perivenular sparing (tigroid pattern)

Volume loss late in disease

Optic nerve enlargement

Can have cranial nerve enhancement

Final Diagnosis

• Metachromatic Leukodystrophy

A. Charcot-Marie-Tooth disease

B. Guillain-Barrè (Miller –Fisher) syndrome

C. Lyme disease

D. Metachromatic leukodystrophy

E. Krabbe Disease

What is your diagnosis?

D. Metachromatic Leukodystophy

Correct Diagnosis

Case 3

Dr. Bruno Soares

Team Gray Matter

Case 3

• Previously healthy 11 year old boy

• New onset sleep walking

• Headache

• Seizure

Case 3 (At Presentation)

Case 3 (Timeline)

Initial 1 month 5 years 4 months

Treatment with steroids

Findings

• T2 hyperintense signal and

expansion of the splenium

• Sparing of the cortex

• Patchy enhancement

• No significant reduced diffusion

Findings

Initial 1 month 5 years 4 months

Treatment with steroids

Absence of global atrophy suggests

patient did not receive RxT

A. Glioblastoma multiforme

B. Tumefactive demyelination

C. Lymphoma

D. Marchiafava-Bignami disease

E. PML

What is your diagnosis?

Differential “ - GBM

Differential “ - GBM

GBM in a 12 year-old boy.

Expansion of adjacent cortex.

Death 14 months after presentation.

Yiu E M et al. J Child Neurol 2013

Our case: 11 year-old boy.

Sparing of adjacent cortex.

Volume loss 5 years later.

VS

16 year-old girl presenting with right-sided weakness, visual disturbance over a week

Differential ” - Tumefactive

Demyelination

• Large lesions with little mass effect; sparing of the cortex

• Cavitation of affected white matter

• Leading edge, incomplete rim of enhancement and reduced diffusion

Differential ” - Tumefactive

Demyelination

• “Myelinoclastic diffuse sclerosis” Schilder’s disease

• 39 patients

– Seizures in 6 patients

– Frontal, parietal and callosum

– Open ring enhancement in 38%

Naggapa et al. Acta Neurol Scand 2013

Differential C - CNS Lymphoma

Differential C - CNS Lymphoma

Differential C - CNS Lymphoma

• Median age of onset: 60-65 years in

immunocompetent patients

• > 96% are Diffuse Large B-cell

• Dramatic initial response to steroids

– False negative biopsy

• Median survival with supportive care, including

steroids: 3 months

• Survival with chemo / RxT: nearly 70% in

patients younger than 60

• Spontaneous remission is exceedingly rare

Schafer et. Al, Expert Rev Neurother 2012

Differential D - Marchiafava-Bignami

Courtesy Dr. Seena Dehkharghani Emory University, Atlanta, GA

• Alcoholic or malnourished male patients

• Callosal demyelination and necrosis, mainly of central fibers

– May involve optic chiasm, AC, CSO and MCPs

– May have associated Wernicke or CPM findings

• Early vitamin B1 supplementation improves prognosis

Differential D - Marchiafava-Bignami

Differential E - PML

12 year-old girl, HIV+, JC virus in CSF

50 year-old male, HIV+, CD4 count 70; JC virus in CSF

Differential E - PML

Final Diagnosis

Tumefactive

Demyelination

A. Glioblastoma multiforme

B. Tumefactive demyelination

C. Lymphoma

D. Marchiafava-Bignami disease

E. PML

What is your diagnosis?

B. Tumefactive Demyelination

Correct Diagnosis

Case 4

Dr. Chen Hoffman

Team White Matter

Case 4

• 4 year old boy

• Progressive cerebral ischemic symptoms

Case 4

Findings

• Both internal carotid arteries are thin or

absent, both MC“ s are narrowed

• Rich collateral arterial network

• Early venous filling, suggestive of AVF

• Large arteries beyond the puff of smoke

• Abnormal signal in the white matter and

atrophy, suggestive of ischemic changes

A. Moyamoya vasculopathy

B. Proliferative angiopathy

C. Hemangioma related arteriopathy

D. Vasculitis

E. Takayasu arteritis

What is your diagnosis?

Moyamoya vasculopathy

• Narrowing of distal ICA and proximal

ACA and MCA

• Multi-infarct disease, in more than 1 essel

teritory

• puff of smoke - collateral arteries-

lenticulostriate and thalamoperforators

arteries

Moyamoya vasculopathy

• Peak incidence age 5 and 5th decade

• In syndromes: NF1, Down syndrome

• Treatment: ansthomosis between ECA and

meningeal arteries

Moyamoya vasculopathy

Proliferative angiopathy

• presumed diagnosis for a peculiar type of

large brain arteriovenous malformations

(AVMs)

• Stenosis of the peroximal arteries (distal

ICA and proximal ACA and MCA)

• Large nidus or fuzzy apperance of nidus

• One or more lobes are involved

Stroke. 2008 Mar;39(3):878-85. doi: 10.1161/STROKEAHA.107.493080. Epub 2008 Jan 31

Pierre L. Lasjaunias,

Proliferative angiopathy

Stroke. 2008 Mar;39(3):878-85. doi:

10.1161/STROKEAHA.107.493080. Epub 2008 Jan

31

Pierre L. Lasjaunias, et al

Hemangioma related

arteriopathy

• PHACE syndrome

• Hemangioma on the facial skin

• Asociated with stenosis of major cerebral

arteries, with Moyamoya vasculopathy

• Midline anomalies

• Occular annomalies

• Consensus Statement on Diagnostic Criteria for PHACE Syndrome

Denise Metry, MDa

2009 Pediatrics Vol. 124 No. 5 November 1, 2009

pp. 1447 -1456

Vasculitis

• Primary CNS vasculitis with abnormal

angiographic studies

• Areas if focal arterial stenosis or occlusion

• Progressive disease or monophasic

• In progressivw type more arteries are

involved in FU scans

• Monophasic scan 1 eposode of focal and in

one hemisphere arterial involment

Vasculitis

• Focal abnormal signal lesions in vascular

territories

• Diagnosis: angiography or MRA

• No AVF reported

Vasculitis

AJNR Am J Neuroradiol 20:75–85, January 1999

Martin G. et al

Takayasu arteritis

• Granulomatous arteritis peak age 2-3

decades, more in women

• Arteries involved- subclavian, carotid,

vertebral mainly in the neck

• Thickening of the arterial wall

• Intracranial involvement is rare

The limited role of MRI in long-term follow-up of patients with Takayasu's arteritis.

Eshet Y, Pauzner R, Goitein O, Langevitz P, Eshed I, Hoffmann C, Konen E.

Autoimmun Rev. 2011 Dec;11(2):132-6

Takayasu arteritis

AVF with arterial pathology

• Acta Clin Croat 2011; 50:115-120 Case Report MOYAMOYA SYNDROME

WITH ARTERIOVENOUS DURAL FISTULA AFTER HEAD TRAUMA

Marjan Zaletel1, Katarina Surlan-Popović2, Janja Pretnar-Oblak1 and

”ojana Žvan1

• A rare case of cerebral proliferative angiopathy with bihemispheric

morphology Jolandi Van Heerden, MBChB, FRANZCR, Andrew Cheung,

MBBS, FRANZCR and Constantine Chris Phatouros, MBBS, FRANZCR

• All 3 other DD poss. and correlation with AVF not found

Final Diagnosis

Proliferative angiopathy

A. Moyamoya vasculopathy

B. Proliferative angiopathy

C. Hemangioma related arteriopathy

D. Vasculitis

E. Takayasu arteritis

What is your diagnosis?

B. Proliferative Angiopathy

Correct Diagnosis

Case 5

Dr. Kling Chong

Team Gray Matter

• 4-year-old boy

• Slowly progressive spasticity, dystonia, ataxia

• Moderate cognitive deficit

Case 5 Provided by Andrea Rossi

Findings

• Diffuse abnormality of white matter signal (for aged 4)

– Subcortical, deep, periventricular and capsular WM involved

– More abnormal on T2w than on T1w

– Leukodystrophy with a ‘hypomyelination’ pattern

• Cerebellar atrophy / hypoplasia

• ? Thalamus hyperintense on T1

• Bilateral putaminal atrophy

• No enhancement

A. Pelizaeus-Merzbacher disease

B. 4H syndrome

C. HABC

D. Vanishing white matter disease

E. Ataxia-telangiectasia

What is your diagnosis?

Differential “ – Pelizaeus-Merzbacher

Disease • PLP1 gene: myelin specific proteolipid

protein 1 and isoform DM20

• Gene duplication (50-70%) or point

mutation (20%)

• Forms:

– Classic (X-linked recessive)

– Connatal (X-linked recessive or

autosomal recessive)

• Severity depends on type of mutation

and whether the proteins are trapped

in the endoplasmic reticulum

• Presentation: abnormal eye

movements, spasticity

• Imaging: Characteristic lack of

myelination

21 month old

Normal term newborn

Pelizaeus-Merzbacher disease 10 month old with nystagmus, hypotonia, dev delay- PMD with triple duplication

Differential ” – 4H syndrome Hypomyelination, hypogonadotropic hypogonadism and hypodontia

• a.k.a. Ataxia, hypodontia and

hypomyelination (AHH) and

Ataxia, delayed dentition and

hypomyelination (ADDH)

• Possible recessive inheritance,

POLR3A/B mutations

• Late walking, early & progressive

ataxia, dysarthria, later spasticity,

rarely seizures, myopia

• Delayed dentition, hypodontia,

molars erupt before incisors

• Absent or delayed puberty

Yang E & Prabhu SP. Imaging Manifestations of the

Leukodystrophies, Inherited Disorders of White Matter.

Radiol Clin N Am 52 (2014) 279–319

4H syndrome is distinguished

from PMD, PMLD, and

HCC by myelination of the

optic radiations and posterior

limb of the internal capsule

with cerebellar atrophy and

prominent T2 hypointensity

of the ventrolateral thalamus

Age 3 Months

Age 3 Years

Courtesy Dr A Siddiqui, St Thomas Hospital, London

4H syndrome

4 y.o. with hypotonia and motor delay

Age 3 Months

Age 3 Years

Courtesy Dr A Siddiqui, St Thomas Hospital, London

Differential C – H-ABC Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC).

• Progressive neurological disorder

with spasticity, dystonia, later

ataxia. Better mental than motor

function

• Sporadic cases, TUBB4A mutations

• Distinctive MRI findings:

hypomyelination pattern, variable

white matter atrophy, small

caudate and putamen, cerebellar

atrophy

M14y, H-ABC (not proven)

Differential D – Vanishing white matter disease

• ARecessive. EIF2B1-5 genes

implicated

• Variable clinical onset. Progressive

stepwise deterioration precipitated

by pyrexia or trauma. Motor and

vision involved +/- seizures, coma.

Ataxia and variable spasticity

• Distinctive MRI findings:

Diffuse hypomyelination with

subsequent cystic WM degeneration.

Normal WM volume.

• Cerebellar atrophy possible.

M3y, spastic quadriplegia;

presented at 9m with

spasticity and progressive

stepwise motor

deterioration

a.k.a. Childhood ataxia with central hypomyelination (CACH)

Differential D – Vanishing white matter disease

9yo boy, Strands of tissue on FLAI‘, no enhancement; no reduced diffusion

Differential E – Ataxia-Telangiectasia

F11y Gait disorder. Progressive clinical and

radiological cerebellar disease. • ARecessive inheritance. ATM gene

• Ataxia usually before aged 5, myoclonus, chorea, oculomotor apraxia

• Telangiectasia – skin and sclera; poor immunity, chronic lung disease

• Raised serum AFP, Impaired DNA repair, increased risk of leukemia, lymphoma, radiation sensitivity.

• MRI findings: Cerebellar atrophy in early stage.

• Later, white matter changes and telangiectasia.

Final Diagnosis

H-ABC

Hypomyelination with atrophy of the

basal ganglia and cerebellum

A. Pelizaeus-Merzbacher disease

B. 4H syndrome

C. HABC

D. Vanishing white matter disease

E. Ataxia-telangiectasia

What is your diagnosis?

C. HABC

Correct Diagnosis

Case 6

Dr. Arastoo Vossough

Team White Matter

Case 6

• 18 year old male

• 1 year history of right thumb numbness

• Abnormal EMG in myotomes of both

upper extremities from C5-T1

Case 6

A. Dural/Epidural AVM/AVF

B. Epidural lipomatosis

C. Epidural abscess

D. Hirayama disease

E. CLOVES syndrome

What is your diagnosis?

Findings

• MRI in flexion shows abnormal

low signal structures in the

posterior epidural space with

narrowing of thecal sac

• Asymmetric thinning/compression

of the cord – abnormal dark

structures in epidural space

Dural and Epidural AVF

Dural AVF: derive arterial blood from radiculomeningeal

branches of segmental spinal arteries, and the fistula is

usually located within the dural sleeve of an exiting nerve

root. The venous drainage is retrograde toward the spinal

cord through the radiculomedullary veins.

Rare in children

Rare in cervical spine

Exclusive Epidural AVF: fed by metameric (segmental)

branches and drain only into the epidural and paravertebral

venous plexuses with no reflux into dural and intradural

venous components.

Typically present with epidural hematoma

This type is extremely rare

Spinal Epidural Abscess

Hematogenous or direct spread

Etiologies:

Staph aureus most common

Mycobacterium TB 2nd most frequent

Others

Location:

Lower thoracic and lumbar > cervical and upper

thoracic

Imaging:

Peripherally enhancing necrotic abscess

Restricted diffusion

Spinal Epidural Lipomatosis

Etiologies:

Long term exogenous steroids most common

Excessive endogenous steroid production

Obesity

Idiopathic

Location:

Thoracic spine: ~60%%

Lumbar spine: ~40%

Cervical: rare

Uncommon in children compared to adults

Hirayama Disease Names:

Monomelic amyotrophy,

Juvenile asymmetric segmental spinal

muscular atrophy

Cervical myelopathy related to anterior

displacement of posterior cervical dura

with flexion

Imaging:

Asymmetric cord atrophy

Flexion study shows increased posterior

epidural space with ventral dural

displacement, cord compression

Enlarged posterior epidural space and

veins with flexion

Hirayama, K et al. Psychiatr Neurol Jpn 1959;61:2190 –2197

CLOVE(S) Syndrome

Congenital, Lipomatous, Overgrowth, Vascular Malformations, Epidermal Nevi and

Spinal/Skeletal Anomalies and/or Scoliosis

1. Sapp JC et al. 2007. AmJ Med Genet Part A 143A: 2944-2958.

2. Alomari AI. 2009. Clin Dysmorphol;18:1-7.

Final Diagnosis

• Hirayama Disease

A. Dural/Epidural AVM/AVF

B. Epidural lipomatosis

C. Epidural abscess

D. Hirayama disease

E. CLOVES syndrome

What is your diagnosis?

D. Hirayama Disease

Correct Diagnosis

Case 7

Dr. Bruno Soares

Team Gray Matter

Case 7

• 2 month old male

• Pierre-Robin sequence

– Micrognathia, glossoptosis, cleft palate

• New onset seizures

Case 7

A. Pelizaeus-Merzbacher disease

B. Maple syrup urine disease

C. Profound hypoxic-ischemic injury

D. Menke disease

E. Leigh disease

What is your diagnosis?

Findings

• T2 hypointense thalami (and putamina)

• Diffuse T2 hyperintensity WM

• Patent but tortuous arteries

• Lactate peak on MRS (TE 144 ms)

Differential “ – Pelizaeus-Merzbacher

Disease

• Lack of myelin formation

• Normal WM volume

21 month-old male with PMD Normal term newborn

Pelizaeus-Merzbacher disease 10 month old with nystagmus, hypotonia, dev delay- PMD with triple duplication

Differential ” - Maple Syrup Urine

Disease

• Leucine encephalopathy

• Defect in decarboxylation of

branched chain amino acids

• Variable clinical phenotype

• Requires lifelong dietary restriction

• MRI:

• Cytotoxic edema in myelinated WM

• Vasogenic edema in remainder of

supratentorial WM

3 week-old, alternating hypotonia and

opisthotonus, seizures

Branched chain amino

acids at 0.9ppm

Spectroscopy in MSUD

Differential C – Profound

HIE

Day 2 after injury: Reduced diffusion in posterior putamina,

ventrolateral thalami, corticospinal tracts

Profound HIE - Basal Ganglia pattern

Different baby – 8 days after injury

Differential D – Menkes

Disease • A.K.A. Trichopoliodystrophy

• Disorder of transmembrane copper

transport

• X-linked recessive (Xq13.3)

• ATP7A gene codes for MNK protein

• Diffusely abnormal WM

• Lactate on MRS

– Anaerobic glycolysis

– Not specific of mitochondrial disorders

• Rapid brain atrophy predisposing

to subdural hematomas

– DDx: Non-accidental trauma and

Glutaric Aciduria type I

Male, 5m

Seshadri R et al. Neurology 2013;81:e12-e13d

Male, 3yo

• Copper is a co-factor in:

• Mitochondrial enzymes

• CNS degeneration

• Basal ganglia involvement

• Elastin-collagen formation

• Fragile, tortuous vessels

• Predisposition to ischemia

• Labs:

• Copper deficiency in blood

• Low ceruloplasmin

• Oral / IV supplementation is not effective

Differential D – Menkes

Disease

Male, 11w, seizures

Follow up @ 2 years

• Born in Vienna

• Family migrated to Ireland in 1939

• MD at Johns Hopkins, 1952

• Internship at Boston Children s

• Established Pediatric Neurology

program at UCLA in 1966

• MSUD (while an intern!)

• Menkes Disease

John H. Menkes, MD (1928-2008)

Pediatrics. 1962 May;29:764-79.

A sex-linked recessive disorder with retardation of growth, peculiar hair,

and focal cerebral and cerebellar degeneration.

Differential E – Leigh Disease

Female, 7m, born at term. Failure to thrive, hypotonia

Final Diagnosis

Menkes

Disease

A. Pelizaeus-Merzbacher disease

B. Maple syrup urine disease

C. Profound hypoxic-ischemic injury

D. Menke disease

E. Leigh disease

What is your diagnosis?

D. Menke Disease

Correct Diagnosis

Case 6

Dr. Chen Hoffman

Team White Matter

Case 8

• 35 week gestation fetus

• Bilateral club feet

• Normal karyotype

• Abnormal fetal US

Case 8

Case 8 (DOL 1)

Case 8 (10 y.o.)

Findings (prenatal)

• Small posterior fossa, abnormal brain stem,

almost z shaped

• Abnormal vermis

• 4th ventricle is wide, cerebellar atrophy

• Abnormal 3rd ventricle, no hydrocephalus

• Abnormal sulcation with thick cortex

• Corpus callosum is not agenetic

Findings (postnatal)

• Cobble stone lissencephaly

• Small posterior fossa

• Atrophy of the brain stem and cerebellum

• Atrophy is more pronounced in the late

MR scan

• Corpus callosum is shown

Dandy-Walker malformation

• Posterior fossa is enlarged

• Vermian hypoplasia

• Counter clock wise rotation of the vermis

• Cystic dilatation of the 4th ventricle

• Associated anomalies: agenesis of corpus

callosum, hydrocephalus,

holoprosencephaly, encephalocele, cleft lip

and palate

Dandy-Walker malformation

X-linked lissencephaly

• Smooth brain

• Cortex is thick

• Callosal agenesis

• Ambiguous genitalia

X-linked lissencephaly

Ann Neurol 2002;51:340–349

Dominique Bonneau, MD et al

Walker-Warburg syndrome

• Thick cortex with few shallow sulci

• Ocular abnormalities

• Corpus callosum hypoplasia

• Hypomyelinatiom

• POMT1 and FCMD mutations

• Most patients die within 1st year of life

Walker-Warburg syndrome

Age of 1 week

Lobar holoprosencephaly

• Failure of differentiation and cleavage of

the brain

• Caused by teratogens and genetic factors

• Hypothalamic- pituitary dysfunction

• Interhemispheric fissure- lack of seperation

of the cerebral hemispheres

Lobar holoprosencephaly

Lobar holoprosencephaly

Final Diagnosis

• Walker-Warburg syndrome

A. Dandy-Walker malformation

B. X-linked lissencephaly

C. Walker-Warburg syndrome

D. Lobar holoprosencephaly

What is your diagnosis?

C. Walker-Warburg syndrome

Correct Diagnosis