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 What is your diagnosis? A. Hypoglycemia
B. Thrombo-embolic infarction
C. Herpes Simplex infection
D. MELAS
E. Hypoxic-ischemic brain injury
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 Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes
7 y.o. - Recent seizures, transient visual symptoms
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 What is your diagnosis? A. Hypoglycemia
B. Thrombo-embolic infarction
C. Herpes Simplex infection
D. MELAS
E. Hypoxic-ischemic brain injury
Correct Diagnosis
C. Herpes Simplex infection
Case 2 Dr. Arastoo Vossough Team White Matter Case 2 (At Presentation) Provided by Andrea Rossi
• 21-month-old girl
• Acute, progressive strabismus
• N.E: muscle hypotonia, brisk tendon reflexes, supported walking, ataxia
• Lab: transaminases, γGT MRI at 21 months Case 2 (Continued)
• 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 MRI at 26 months Case 2 (Continued)
• Intravenous immunoglobulin treatment with little benefit
• 3 years: seizures, dysphagia, difficult speech, mental deterioration, severe muscle hypotonia and weakness, inability to stand and walk 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 What is your diagnosis? A. Charcot-Marie-Tooth disease
B. Guillain-Barrè (Miller –Fisher) syndrome C. Lyme disease
D. Metachromatic leukodystrophy
E. Krabbe Disease
Correct Diagnosis
D. Metachromatic Leukodystophy
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 4 months 5 years
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 4 months 5 years
Treatment with steroids Absence of global atrophy suggests patient did not receive RxT
What is your diagnosis? A. Glioblastoma multiforme
B. Tumefactive demyelination
C. Lymphoma
D. Marchiafava-Bignami disease
E. PML
Differential “ - GBM Differential “ - GBM
VS
GBM in a 12 year-old boy. Our case: 11 year-old boy. Expansion of adjacent cortex. Sparing of adjacent cortex. Death 14 months after presentation. Volume loss 5 years later.
Yiu E M et al. J Child Neurol 2013 Differential ” - Tumefactive Demyelination
16 year-old girl presenting with right-sided weakness, visual disturbance over a week
• 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
• 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 Courtesy Dr. Seena Dehkharghani Emory University, Atlanta, GA
Differential D - Marchiafava-Bignami Differential E - PML
12 year-old girl, HIV+, JC virus in CSF Differential E - PML
50 year-old male, HIV+, CD4 count 70; JC virus in CSF Final Diagnosis
Tumefactive Demyelination What is your diagnosis? A. Glioblastoma multiforme
B. Tumefactive demyelination
C. Lymphoma
D. Marchiafava-Bignami disease
E. PML
Correct Diagnosis
B. Tumefactive Demyelination
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 What is your diagnosis? A. Moyamoya vasculopathy
B. Proliferative angiopathy
C. Hemangioma related arteriopathy
D. Vasculitis
E. Takayasu arteritis
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
What is your diagnosis? A. Moyamoya vasculopathy
B. Proliferative angiopathy
C. Hemangioma related arteriopathy
D. Vasculitis
E. Takayasu arteritis
Correct Diagnosis
B. Proliferative Angiopathy
Case 5 Dr. Kling Chong Team Gray Matter Case 5 Provided by Andrea Rossi
• 4-year-old boy
• Slowly progressive spasticity, dystonia, ataxia
• Moderate cognitive deficit
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 What is your diagnosis?
A. Pelizaeus-Merzbacher disease
B. 4H syndrome
C. HABC
D. Vanishing white matter disease
E. Ataxia-telangiectasia
Differential “ – Pelizaeus-Merzbacher
Disease 21 month old • 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 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, 4H syndrome is distinguished molars erupt before incisors from PMD, PMLD, and HCC by myelination of the Absent or delayed puberty • optic radiations and posterior limb of the internal capsule with cerebellar atrophy and Yang E & Prabhu SP. Imaging Manifestations of the prominent T2 hypointensity Leukodystrophies, Inherited Disorders of White Matter. of the ventrolateral thalamus Radiol Clin N Am 52 (2014) 279–319 4H syndrome Age 3 Months
Age 3 Years 4 y.o. with hypotonia and motor delay Courtesy Dr A Siddiqui, St Thomas Hospital, London 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 a.k.a. Childhood ataxia with central hypomyelination (CACH)
• 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. M3y, spastic quadriplegia; Normal WM volume. presented at 9m with spasticity and progressive • Cerebellar atrophy possible. stepwise motor deterioration 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 • ARecessive inheritance. ATM gene radiological cerebellar disease. • 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 What is your diagnosis?
A. Pelizaeus-Merzbacher disease
B. 4H syndrome
C. HABC
D. Vanishing white matter disease
E. Ataxia-telangiectasia
Correct Diagnosis
C. HABC
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 What is your diagnosis? A. Dural/Epidural AVM/AVF
B. Epidural lipomatosis
C. Epidural abscess
D. Hirayama disease
E. CLOVES syndrome
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 What is your diagnosis? A. Dural/Epidural AVM/AVF
B. Epidural lipomatosis
C. Epidural abscess
D. Hirayama disease
E. CLOVES syndrome
Correct Diagnosis
D. Hirayama Disease
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 What is your diagnosis? A. Pelizaeus-Merzbacher disease
B. Maple syrup urine disease
C. Profound hypoxic-ischemic injury
D. Menke disease
E. Leigh disease
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 Spectroscopy in MSUD
Branched chain amino acids at 0.9ppm 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 Male, 5m • Lactate on MRS – Anaerobic glycolysis – Not specific of mitochondrial disorders • Rapid brain atrophy predisposing Seshadri R et al. Neurology 2013;81:e12-e13d to subdural hematomas – DDx: Non-accidental trauma and Glutaric Aciduria type I
Differential D – Menkes Disease • 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
Male, 3yo
Male, 11w, seizures Follow up @ 2 years John H. Menkes, MD (1928-2008)
• 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 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 What is your diagnosis? A. Pelizaeus-Merzbacher disease
B. Maple syrup urine disease
C. Profound hypoxic-ischemic injury
D. Menke disease
E. Leigh disease
Correct Diagnosis
D. Menke Disease
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
What is your diagnosis?
A. Dandy-Walker malformation
B. X-linked lissencephaly
C. Walker-Warburg syndrome
D. Lobar holoprosencephaly
Correct Diagnosis
C. Walker-Warburg syndrome