2014 asnr aspnr interesting case session

1. ASPNR
INTERESTING
CASE SESSION
2014
ASNR 52nd
ANNUAL
MEETING
May 17-22, 2014
Montreal,
Quebec, Canada

2. ASPNR Interesting Case Session
Dr. Kling Chong
Dr. Arastoo Vossough
Dr. Bruno Soares
Dr. Chen Hoffman

3. Case 1
Dr. Kling Chong
Team “Gray Matter”

4. Case 1
• 13 month old girl
• 4 day history of vomiting and fever
• Status epilepticus

5. Case 1 (Day of Admission)

6. Case 1 (Day of Admission)
PCASL Rel CBF

7. Case 1 (21 days later)

8. 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

9. 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

10. A. Hypoglycemia
B. Thrombo-embolic infarction
C. Herpes Simplex infection
D. MELAS
E. Hypoxic-ischemic brain injury
What is your diagnosis?

11. Differential ‘A’ - Hypoglycemia
15 month-old girl presenting with seizures
Congenital adrenal hyperplasia

12. Acute Brain Injury in Hypoglycemia

13. Chronic Brain Injury from Hypoglycemia
9 year-old girl with history of insulinoma s/p resection, now with first time seizure

14. Differential ‘B’ - Thrombo-embolic
infarction
30 month old girl with right hemiplegia for 3 days
Sickle Cell Disease; acute, subacute and chronic arterial ischemic stroke

15. Chronic Injury from infarction
Meningitis with venous infarcts

16. Differential ‘C’ – Herpes simplex infection
10 year old girl - H Simplex encephalitis; HSV by DNA in CSF on PCR

17. 11 yo HSV

18. Differential ‘D’ - MELAS
7 y.o. - Recent seizures, transient visual symptoms
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes

20. Differential ‘E’ – Hypoxic-ischemic
brain injury
12 month old girl - Cardiac arrest during induction for cardiac surgery;
23 mins down time; MRI day 5

21. HIE – Day 2 of life

22. Final Diagnosis
Herpes Simplex
Infection

23. HIE – @ 4 weeks
1 month old; premature 36 week;
parechovirus infection with cardiovascular collapse @ 4 weeks
Age 4 weeks Age 4 years

24. A. Hypoglycemia
B. Thrombo-embolic infarction
C. Herpes Simplex infection
D. MELAS
E. Hypoxic-ischemic brain injury
What is your diagnosis?

25. C. Herpes Simplex infection
Correct Diagnosis

26. Case 2
Dr. Arastoo Vossough
Team “White Matter”

27. • 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

28. MRI at 21 months

29. • 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)

30. MRI at 26 months

31. • 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)

32. MRI at 36 months

33. Brain MRI at 36 months

34. What is your diagnosis?
A. Charcot-Marie-Tooth disease
B. Guillain-Barrè (Miller –Fisher) syndrome
C. Lyme disease
D. Metachromatic leukodystrophy
E. Krabbe Disease

35. 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

36. 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

37. Charcot-Marie-Tooth Disease
X-linked subtype can have
brain signal abnormalities
White matter T2
hyperintensities and restricted
diffusion

38. 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

39. 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

40. 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

41. 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

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

43. 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

44. Lyme’s Disease
Neuroborreliosis
Imaging:
White matter lesions (may enhance)
Multiple enhancing cranial nerves
(CN VII most common)
Meningeal enhancement
Cauda equina enhancement

45. 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

46. Final Diagnosis
• Metachromatic Leukodystrophy

47. A. Charcot-Marie-Tooth disease
B. Guillain-Barrè (Miller –Fisher) syndrome
C. Lyme disease
D. Metachromatic leukodystrophy
E. Krabbe Disease
What is your diagnosis?

48. D. Metachromatic Leukodystophy
Correct Diagnosis

49. Case 3
Dr. Bruno Soares
Team “Gray Matter”

50. Case 3
• Previously healthy 11 year old boy
• New onset sleep walking
• Headache
• Seizure

51. Case 3 (At Presentation)

52. Case 3 (Timeline)
Initial 1 month 5 years4 months
Treatment with steroids

53. Findings
• T2 hyperintense signal and
expansion of the splenium
• Sparing of the cortex
• Patchy enhancement
• No significant reduced diffusion

54. Findings
Initial 1 month 5 years4 months
Treatment with steroids
Absence of global atrophy suggests
patient did not receive RxT

55. A. Glioblastoma multiforme
B. Tumefactive demyelination
C. Lymphoma
D. Marchiafava-Bignami disease
E. PML
What is your diagnosis?

56. Differential ‘A’- GBM

57. Differential ‘A’- 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

58. 16 year-old girl presenting with right-sided weakness, visual disturbance over a week
Differential ‘B’- 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

59. Differential ‘B’- 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

60. Differential ‘C’- CNS Lymphoma

61. Differential ‘C’- CNS Lymphoma

62. 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

63. 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

64. Differential ‘D’- Marchiafava-Bignami

65. Differential ‘E’- PML
12 year-old girl, HIV+, JC virus in CSF

66. 50 year-old male, HIV+, CD4 count 70; JC virus in CSF
Differential ‘E’- PML

67. Final Diagnosis
Tumefactive
Demyelination

68. A. Glioblastoma multiforme
B. Tumefactive demyelination
C. Lymphoma
D. Marchiafava-Bignami disease
E. PML
What is your diagnosis?

69. B. Tumefactive Demyelination
Correct Diagnosis

70. Case 4
Dr. Chen Hoffman
Team “White Matter”

71. Case 4
• 4 year old boy
• Progressive cerebral ischemic symptoms

72. Case 4

73. Findings
• Both internal carotid arteries are thin or
absent, both MCA’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

74. A. Moyamoya vasculopathy
B. Proliferative angiopathy
C. Hemangioma related arteriopathy
D. Vasculitis
E. Takayasu arteritis
What is your diagnosis?

75. 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

76. Moyamoya vasculopathy
• Peak incidence age 5 and 5th
decade
• In syndromes: NF1, Down syndrome
• Treatment: ansthomosis between ECA and
meningeal arteries

77. Moyamoya vasculopathy

78. 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,

79. Proliferative angiopathy
Stroke. 2008 Mar;39(3):878-85. doi:
10.1161/STROKEAHA.107.493080. Epub 2008 Jan
31
Pierre L. Lasjaunias, et al

80. 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

81. 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

82. Vasculitis
• Focal abnormal signal lesions in vascular
territories
• Diagnosis: angiography or MRA
• No AVF reported

83. Vasculitis
AJNR Am J Neuroradiol 20:75–85, January 1999
Martin G. et al

84. 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

85. Takayasu arteritis

86. 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
Bojana 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

87. Final Diagnosis
Proliferative angiopathy

88. A. Moyamoya vasculopathy
B. Proliferative angiopathy
C. Hemangioma related arteriopathy
D. Vasculitis
E. Takayasu arteritis
What is your diagnosis?

89. B. Proliferative Angiopathy
Correct Diagnosis

90. Case 5
Dr. Kling Chong
Team “Gray Matter”

91. • 4-year-old boy
• Slowly progressive spasticity, dystonia,
ataxia
• Moderate cognitive deficit
Case 5
Provided by Andrea Rossi

93. 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

94. A. Pelizaeus-Merzbacher disease
B. 4H syndrome
C. HABC
D. Vanishing white matter disease
E. Ataxia-telangiectasia
What is your diagnosis?

95. Differential ‘A’ – 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

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

97. Differential ‘B’ – 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

98. Age 3 Months
Age 3 Years
Courtesy Dr A Siddiqui, St Thomas Hospital, London
4H syndrome
4 y.o. with hypotonia and motor delay

99. Age 3 Months
Age 3 Years
Courtesy Dr A Siddiqui, St Thomas Hospital, London

100. 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)

101. 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)

102. Differential ‘D’ – Vanishing white matter disease
9yo boy, ‘Strands’ of tissue on FLAIR,
no enhancement; no reduced diffusion

103. 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.

104. Final Diagnosis
H-ABC
Hypomyelination with atrophy of the
basal ganglia and cerebellum

105. A. Pelizaeus-Merzbacher disease
B. 4H syndrome
C. HABC
D. Vanishing white matter disease
E. Ataxia-telangiectasia
What is your diagnosis?

106. C. HABC
Correct Diagnosis

107. Case 6
Dr. Arastoo Vossough
Team “White Matter”

108. Case 6
• 18 year old male
• 1 year history of right thumb numbness
• Abnormal EMG in myotomes of both
upper extremities from C5-T1

109. Case 6

110. A. Dural/Epidural AVM/AVF
B. Epidural lipomatosis
C. Epidural abscess
D. Hirayama disease
E. CLOVES syndrome
What is your diagnosis?

111. 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

112. 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

113. 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

114. 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

115. 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

116. 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.

117. Final Diagnosis
• Hirayama Disease

118. A. Dural/Epidural AVM/AVF
B. Epidural lipomatosis
C. Epidural abscess
D. Hirayama disease
E. CLOVES syndrome
What is your diagnosis?

119. D. Hirayama Disease
Correct Diagnosis

120. Case 7
Dr. Bruno Soares
Team “Gray Matter”

121. Case 7
• 2 month old male
• Pierre-Robin sequence
– Micrognathia, glossoptosis, cleft palate
• New onset seizures

122. Case 7

123. A. Pelizaeus-Merzbacher disease
B. Maple syrup urine disease
C. Profound hypoxic-ischemic injury
D. Menke disease
E. Leigh disease
What is your diagnosis?

124. Findings
• T2 hypointense thalami (and putamina)
• Diffuse T2 hyperintensity WM
• Patent but tortuous arteries
• Lactate peak on MRS (TE 144 ms)

125. Differential ‘A’ – Pelizaeus-Merzbacher
Disease
• Lack of myelin formation
• Normal WM volume
21 month-old male with PMD Normal term newborn

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

127. Differential ‘B’- 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

128. Branched chain amino
acids at 0.9ppm
Spectroscopy in MSUD

129. Differential ‘C’ – Profound
HIE
Day 2 after injury: Reduced diffusion in posterior putamina,
ventrolateral thalami, corticospinal tracts

130. Profound HIE - Basal Ganglia pattern
Different baby – 8 days after injury

131. 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

132. 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

133. Male, 11w, seizures

134. Follow up @ 2 years

135. • 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.

136. Differential ‘E’ – Leigh Disease
Female, 7m, born at term. Failure to thrive, hypotonia

137. Final Diagnosis
Menkes
Disease

138. A. Pelizaeus-Merzbacher disease
B. Maple syrup urine disease
C. Profound hypoxic-ischemic injury
D. Menke disease
E. Leigh disease
What is your diagnosis?

139. D. Menke Disease
Correct Diagnosis

140. Case 6
Dr. Chen Hoffman
Team “White Matter”

141. Case 8
• 35 week gestation fetus
• Bilateral club feet
• Normal karyotype
• Abnormal fetal US

142. Case 8

143. Case 8 (DOL 1)

144. Case 8 (10 y.o.)

145. 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

146. 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

147. 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

148. Dandy-Walker malformation

149. X-linked lissencephaly
• Smooth brain
• Cortex is thick
• Callosal agenesis
• Ambiguous genitalia

150. X-linked lissencephaly
Ann Neurol 2002;51:340–349
Dominique Bonneau, MD et al

151. 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

152. Walker-Warburg syndrome
Age of 1 week

153. 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

154. Lobar holoprosencephaly

155. Lobar holoprosencephaly

156. Final Diagnosis
• Walker-Warburg syndrome

157. A. Dandy-Walker malformation
B. X-linked lissencephaly
C. Walker-Warburg syndrome
D. Lobar holoprosencephaly
What is your diagnosis?

158. C. Walker-Warburg syndrome
Correct Diagnosis