More Than Just Three Pairs of Stalks:
Comprehensive Interactive Case Review of
Bilateral Cerebellar Peduncle
Abnormalities
Yin Jie Chen1, Andreas Rauschecker1, Arastoo
Vossough2, Laurie A. Loevner1, Suyash Mohan1
1.
2.
Department of Radiology, Hospital of the University of Pennsylvania
Department of Radiology, Children’s Hospital of Philadelphia
Control #: 1252
eEdE-02-7538
Disclosure Statement
• No relevant disclosures
Goals & Objectives
• Goals
– Review neurologic diseases exhibiting bilateral superior,
middle, and/or inferior cerebellar peduncle abnormalities
– Illustrate important imaging and clinical features that help
narrow the relevant differential diagnoses
• Objectives
– Review the anatomy of cerebellar peduncles & associated
fiber tracts
– Offer approach to narrow differential diagnoses for
bilateral cerebellar peduncle abnormalities
– Present an interactive case series to improve diagnostic
accuracy
Cerebellar Peduncles*#
• Anatomy, Blood Supply, and Associated Fiber
Tracts
• Interactive Case Series By Age Group
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–
–
–
–
Congenital & Genetic Etiologies
Neurodegenerative Etiologies
Metabolic Etiologies
Infectious & Inflammatory Etiologies
Neoplastic Etiologies
* A stalk bearing a flower or flower cluster or a fructification
# Root in New Latin - pedunculus, diminutive of Latin ped-, pes, first known use, 1702
- Merriam-Webster Dictionary, 2015
MCP
ICP
SCP
SCP
PS
MCP
MCP
ICP
SCP
MCP
ICP
PS
PS
PS
T1 MPRAGE MRI depicting cerebellar peduncles and pons. SCP – superior cerebellar peduncle,
MCP – middle cerebellar peduncle, ICP – inferior cerebellar peduncle, PS – pons.
SCP
SCA
MCP
AICA
ICP
PICA
T1 MPRAGE MRI images depicting vascular territories: basilar artery, superior cerebellar artery
(SCA), anterior inferior cerebellar artery (AICA), & posterior inferior cerebellar artery (PICA).
T
H
SCP
MCP
ICP
A
T
H
P
S
R
F
O
N
P
S
R
F
O
N
SCP
MCP
D
C
ICP
T
H
T
H
R
N
R
N
SCP
SCP
MCP
MCP
ICP
ICP
D
C
B
Main afferent (A) and efferent (B) fiber tracts between cerebral cortex and cerebellum
through cerebellar peduncles. Olivary nucleus – ON, thalamus – TH, red nucleus – RN,
deep cerebellar nucleus – DC, corticopontocerebellar tract, cerebro-olivocerebellar tract,
cerebroreticulocerebellar tract, globose-emboliform-rubral tract, dentothalamic tract.
Important Fiber Tracts
• Corticopontocerebellar tract
– Conveys information on planning
and initiation of movement
– From cerebral cortex to
contralateral cerebellum
• Cerebro-olivocerebellar tract
– Conveys control from cerebral
cortex to cerebellar cortex via
inferior olivary nuclei and climbing
fibers
– Terminate directly on Purkinje cells
• Cerebroreticulocerebellar tract
– Involved in regulation of voluntary
movement
– In particular adjustment of muscle
activity as result of cortical input
– Input primarily from sensorimotor
areas
• Globose-emboliform-rubral tract
– Controls ipsilateral motor activity
– Connection from globose and
emboliform nuclei to contralateral
red nucleus, then crossing via
rubrospinal tract to ipsilateral
motor neurons in spinal cord
• Dentothalamic tract
– Affects ipsilateral motor activity
– Connection from dentate nucleus
to contralateral ventrolateral
nucleus of the thalamus, in turn
connecting to contralateral
cerebral motor cortex
INTERACTIVE CASE SERIES
PEDIATRIC POPULATION
15 M boy with developmental delay, hypotonia, abnormal
breathing patterns, and polydactyly
T1-Pre
T2
T1-Pre
Axial T1 MPRAGE pre-contrast and axial T2 images show “molar tooth” sign with deep
interpeduncular fossa and thick straight SCPs, as well as hypoplastic vermis.
Dx: Joubert Syndrome
Joubert Syndrome
•
Clinical features
–
–
–
–
–
–
–
Autosomal recessive
1 of 13 mutations
in >75%
Patient pos
with
Syndrome
DefectsJoubert
in primary
cilium
Facial dysmorphism
Polydactyly
Most children reach adulthood
Outcome not related to severity of
imaging findings
– Spectrum of abnormalities
•
Diagnostic pearls
– "Molar tooth" sign
• Deep interpeduncular fossa
Patient
•Normal
Thick, straight
SCP
• Hypoplastic vermis
– Absence of fiber decussation
– Joubert Syndrome-related Disorders
• “Molar tooth” sign plus other signs
• Cerebello-oculo-renal syndrome
• COACH syndrome (Coloboma,
oligophrenia, ataxia, cerebellar vermis
hypoplasia, hepatic fibrosis)
• Developmental delay / mental
retardation
• Differential considerations
• Hypotonia
– Dandy-Walker continuum
• Respiratory difficulties
• "Molar tooth" sign not a feature
• Seizures
Diffusion tensor imaging shows absence
decussation
of fibers
– of
Chiari
malformation
• Occulomotor, oral-motor, and speech
(transversely oriented fibers in red) at the
of SCPs
in magna
• level
Obliteration
of cisterna
problems
patient with Joubert Syndrome, compared
to cisterna
normalmagna
patient
– Mega
• No associated malformation
16 Y/M with developmental delay now with progressive gait
abnormality & palatal myoclonus
FLAIR
T1-Pre
T1-Pre
T1-Post
Axial T1 pre-contrast image show intrinsic T1 hyperintensities in the supratentorial deep
white matter. Axial T1 pre and post images demonstrate faint enhancement in deep
cerebellar structures. Axial FLAIR images show supratentorial and infratentorial FLAIR
hyperintensities, with sparing of the deep gray structures and subcortical white matter.
Dx: Alexander Disease
Alexander Disease
• Diagnosed by genetic testing
– GFAP gene (D360H missense mutation for
this patient)
– Autosomal dominant
– Infantile (birth – 2 y/o), juvenile (2-12 y/o),
adult (> 12 y/o) forms
– Accumulation of Rosenthal fibers (RFs) in
astrocytes & hypo-/demyelination
– Diagnostic pearls
• Enhancement in brainstem and cerebellar
peduncles typically exist early in disease course
(non-infantile forms)
• Infantile form more localized abnormalities in
bifrontal white matter
• Rostral-caudal gradient less pronounced in
juvenile/adult forms
Infantile Alexander
Disease with bifrontal
white matter
abnormalities
6 Y/F with severe dystonia, chorea, and slow motor
deterioration over 4 years
T1-Pre
T1-Pre
T1-Pre
T1-Pre
Patient had very elevated manganese levels that responded to
chelation for short periods of time, without any identifiable
exposure source. Therefore she was given the presumed
diagnoses of congenital hypermanganesemia, although no
specific genetic mutation has been able to be identified so far.
Axial T1 pre-contrast images show intrinsic T1 hyperintensities in the basal ganglia,
midbrain, SCP, and cerebellar hemispheres. No signal alterations on other sequences.
Dx: Congenital Hypermanganesemia
Other Congenital & Genetic Etiologies
• Other leukodystrophies
– Krabbe Disease
– X-linked adrenoleukodystrophy
– Mitochondrial leukodystrophy
• Pontine tegmental cap
dysplasia (PTCD)
• Maple syrup urine disease
(MSUD)
Restricted diffusion in
bilateral MCP and
Hypoplasia
of pons and
posterior internal
MCPsininneonate
newbornwith
with
capsule
feeding
difficulty who
MSUD
was diagnosed with
PTCD
INTERACTIVE CASE SERIES
GERIATRIC POPULATION
81 Y/M with progressive gait abnormalities, urinary
incontinence, & cognitive decline
T2
T2
T1-Pre
http://www.sugarspunmarketing.com/wpcontent/uploads/2013/10/hummingbird.jpg
Axial T2 image demonstrates bilateral MCP hyperintensities. Coronal T2 image depicts
diffuse supratentorial and infratentorial volume loss. Sagittal T1 image shows midbrain
atrophy, so called “hummingbird” sign.
Dx: Progressive Supranuclear Palsy
Progressive Supranuclear Palsy (PSP)
• Part of Parkinson-plus syndromes
• Mean age 65 yrs
• Clinical presentation
– Gait instability
– Supranuclear ophthalmoplegia
• Diagnostic pearl – severe midbrain atrophy
• Differential consideration
– Multiple system atrophy (MSA), cerebellar
subtype (MSA-C)
• Also known as, sporadic olivopontocerebellar
atrophy
• Gait ataxia, limb akinetic ataxia, dysarthria,
cerebellar oculomotor disturbance
– Diagnostic pearls
• Atrophy isolated to pons & cerebellum
• “Hot cross bun” sign
62 Y/O M with MSA-C
noting “hot cross bun” sign
Other Neurodegenerative Etiologies
• Spinocerebellar ataxia
• Creutzfeldt-Jakob
disease
• Fragile X-associated
Tremor/Ataxia
Syndrome
• Autosomal recessive
spastic ataxia of
Charlevoix- Saguenay
• Wolfram syndrome
68 Y/O M with gait
instability and
presumed diagnosis of
Fragile X
INTERACTIVE CASE SERIES
ALL AGES
60 Y/F with long history of alcohol abuse present with
headache, speech disturbance, & tremors
Six Months Later
T1-Pre
FLAIR
FLAIR
Axial T1 image shows intrinsic T1 hyperintensity in basal ganglia bilaterally. Axial FLAIR
image demonstrates FLAIR hyperintensity in MCP bilaterally. After receiving proper
treatment, axial FLAIR image from six months later depicts decreased hyperintensity in MCP
bilaterally.
Dx: Hepatic Encephalopathy
Hepatic Encephalopathy
•
•
•
Occurs in severe liver dysfunction
Occurs in more than 50% cirrhotic
patients
Clinical presentation
– Altered mental status
– Motor abnormalities (e.g., tremor, ataxia,
etc)
– Fetor hepaticus
•
Diagnostic pearls
– Liver dysfunction, most commonly caused
by alcohol
– T1 hyperintensity in basal ganglia
•
•
Thought to be secondary to manganese
deposition
Similar to congenital hypermanganesemia
– FLAIR hyperintensity within hemispheric
white matter and corticospinal tract
Companion Case:
31 Y/M with alcohol abuse , tremors, &
Wernicke's encephalopathy (symptoms
improved with thiamine & folate). T2
hyperintensities within bilateral mammillary
bodies and MCP.
Other Metabolic Etiologies
• Wilson disease
• Extra-pontine
myelinolysis
• Hypoglycemia
• Toluene toxicity
23 Y/F with Wilson’s Disease,
noting T1 hyperintensity in
basal ganglia and bilateral MCP
T2 hyperintensity
56 Y/F with AML admitted for acute renal failure presented
with abnormal eye movements
DWI
FLAIR
FLAIR
FLAIR
ADC
Dx: Posterior Reversible Encephalopathy
Syndrome
Axial FLAIR images demonstrate FLAIR hyperintensities in bilateral posterior internal
capsule, right occipital lobe, and MCP. Axial DWI and ADC images depict a focus of restricted
diffusion in right MCP.
Posterior Reversible Encephalopathy
Syndrome (PRES)
• Most commonly seen in acute /
malignant hypertension
– Disruption of auto-regulation
and blood brain barrier
– Several other causes including
drug toxicity
• Diagnostic pearls
– Patchy foci of T1 hypo- and T2
hyper-intensities in posterior
circulation
– Usually only vasogenic edema,
but can have foci of cytotoxic
edema
Companion Case:
Cyclosporine toxicity with FLAIR hyperintensity in
thalami, pons, parieto-occipital white matter &
cerebellum. Note: vasogenic edema
Other Cerebrovascular Etiologies
•• Bilateral
Unknown
anterior
Case One
•Wallerian
Unknown
Case Two
degeneration
POP• QUIZ
inferior
cerebellar
pontocerebellar
What
is the
arterial bloodof
supply
to the MCP?tracts
arteries (AICA) infarct
A. Superior cerebellar artery
B. Anterior inferior cerebellar artery
C. Posterior inferior cerebellar artery
D. Basilar artery
43 Y/F status post TEVAR,
noting bilateral restricted
diffusion in AICA territory
61 Y/M with recent pontine
infarct due to basilar artery
stenosis now with bilateral
MCP FLAIR hyperintensities
60 Y/M with fever, lethargy, nausea, vomiting and difficulty with
micturition; returned from a safari in Tanzania 3 weeks ago
FLAIR
FLAIR
FLAIR images of the brain and spine demonstrate FLAIR hyperintensities in the subcortical /
deep white matter, midbrain, MCP, and spine cord. CSF studies showed 8 RBC, 385 WBC (86%
lymphocytes), Glu 62, Protein 223, and negative Gram stain and culture.
Dx: Acute Disseminated Encephalomyelitis
Acute Disseminated Encephalomyelitis
(ADEM)
• Autoimmune-mediated acute
demyelination
• Prodromal phase (fever, malaise,
myalgia), followed by symptoms
such as headache and drowsiness,
with progression to lethargy or
even coma
• Diagnostic pearls
– Multifocal T2/FLAIR white matter
hyperintensities,
– Possibly also deep grey structures
– Following recent infection, often
viral (can be post-vaccination)
Companion Case:
51 Y/M with AML s/p SCT
with acute encephalopathy
FLAIR hyperintensities in
periventricular WM,
midbrain, and cerebellar
peduncles (bilateral SCP, MCP,
and ICP, top to bottom)
Dx: Immune-mediated Demylination
(Presumed to be related to SCT)
37 Y/F with stiffness in the mornings and leg twitches in the
evenings
Three years ago
T2
Current Study
T2
MRI from three years ago shows scatter periventricular T2 hyperintensities. Current study
shows new T2 hyperintensities involving both ICPS, in addition to the periventricular lesions.
Dx: Multiple Sclerosis
Multiple Sclerosis
•
Demographics
–
–
–
–
Age: 20-40 years
Prevalence: F > M
Caucasian most common
Variable symptoms
•
•
•
•
Weak, numb, tingling, gait disturbance,
Optic neuritis, other cranial nerve palsies
Spinal cord involved in 80%
Diagnostic pearls
– Multiple periventricular/perivenular T2
hyperintensities
•
“Dawson fingers”
– Infratentorial in 10%
– Acutely demyelinating lesions can enhance
(nodular or ring)
– Polyphasic
•
•
•
•
Relapsing-remitting – most common (>80%)
Secondary-progressive
Primary-progressive
Progressive-replapsing – rare
Companion Case:
MS patient with scattered FLAIR
hyperintensities in periventricular white
matter and bilateral MCP
Other Infectious &
Inflammatory Etiologies
•• Neurosarcoidosis
History of sarcoidosis
•• Progressive
multifocal
History of HIV/AIDS
leukoencephalopathy
(PML)
FLAIR hyperintensities and small foci of
enhancement in bilateral MCP in this patient
with transbronchial biopsy proven sarcoidosis
FLAIR hyperintensities in bilateral MCP in this
patient with HIV/AIDS
60 Y/M with renal cell carcinoma present with horizontal
diplopia suspicious for sixth and seventh nerve palsies
T1-Pre
T1-Post
FLAIR
CBV
Short TE MRS
Axial T1 pre and post contrast images shows a heterogeneously enhancing mass centered in
the pons, associated with surrounding FLAIR hyperintensities extending into bilateral MCP,
as well increased relative cerebral blood volume. Short TE MR spectroscopy demonstrates
elevation of lipid-lactate peaks.
Dx: Metastatic RCC
Metastatic RCC
•
•
Stereotactic biopsy - clear cell carcinoma consistent
with renal origin
Diagnostic pearls
– Known primary malignancy, especially with known
metastases elsewhere
– Mass with aggressive features on perfusion and
spectroscopy studies
•
Differential consideration
– Glioma
•
•
Enhancement pattern varies depending on type
Often less surrounding vasogenic edema than metastases
– Lymphoma
•
•
More homogenous enhancement
Usually hyperdense on CT and can show restricted diffusion
– Radiation changes / necrosis
•
•
Expect to decrease over time
Necrosis
–
–
Most often 12-24 months post radiation
Expect very low NAA, Cho, and Cr peaks on MR spectroscopy
FLAIR hyperintensity in
bilateral MCP from
radiation change related to
prior treatment of left
temporal lobe astrocytoma
15 Y/M with tectal pilocytic astrocytoma s/p resection &
proton therapy, now with refusal to speak
Pre-Operative
T1-Pre
Current Exam
T1-Pre
FLAIR
FLAIR
T1-Post
T1-Post
Pre-operative T1-MPRAGE pre-/post-contrast images show avidly enhancing tectal mass.
Post-treatment MRI (when patient presented with mutism) show no residual enhancing
tumor and increased FLAIR signal in the both SCPs.
Dx: Cerebellar Mutism Syndrome
Cerebellar Mutism Syndrome
• Also called posterior fossa
syndrome
• Typically occur after resection
of posterior fossa tumors
• Incidence post midline
posterior fossa tumor
resection as high as 40%
• Clinical symptoms
– Transient mutism (days to
weeks)
– Cognitive & behavioral issues
– Emotional liability
– Persistent ataxia and motor
coordination issues can occur
• Attributed to damage of
bilateral dentate nuclei or
cerebellar output pathways
(SCPs)
• SCPs vulnerable during
resection due to their close
relationship to the 4th ventricle
• Ojemann JG, et al., showed
that diffusion tensor imaging
of SCPs can identify patients
who did and did not develop
cerebellar mutism syndrome
in a small sized patient
population
Conclusions
• SCP, MCP, and ICP are vital to proper communication
between cerebral cortex and cerebellum
• Bilateral cerebellar peduncle abnormalities can be
seen in many disease processes
• Considering image findings in the appropriate clinical
settings is vital in narrowing differential diagnoses
• Diagnostic considerations
– Congenital & genetic causes common in pediatric
population
– Neurodegenerative causes common in geriatric population
– Most other causes can be seen in all age groups
Conclusions
• Disease specific diagnostic pearls
– Congenital & Genetic
• Joubert Syndrome – “Molar tooth” sign
• Alexander Disease - enhancement in brainstem and cerebellar
peduncles early in disease course (non-infantile forms)
• Congenital hypermanganesemia – abnormal heavy metal labs
• Pontine tegmental cap dysplasia – newborn with hypoplasia of
pons and cerebellar peduncles
– Neurodegenerative
• PSP - severe midbrain atrophy, “Hummingbird” sign
• MSA – pons atrophy, “hot cross bun” sign
Conclusions
• Disease specific diagnostic pearls, continued
– Metabolic
• Hepatic encephalopathy – alcohol most common causative agent
• Wilson disease - T1 hyperintensity in basal ganglia
– Cerebrovascular
• PRES – HTN or drug toxicity, posterior circulation abnormalities
• Stroke – AICA territory, rare to have bilateral
• Wallerian degeneration of pontocerebellar tracts – prior pontine
insult
– Infectious & inflammatory
• ADEM – most commonly follow viral infection, monophasic
• MS – multiple lesions separate in space and time
Conclusions
• Disease specific diagnostic pearls, continued
– Neoplastic
•
•
•
•
•
Metastases - Known primary malignancy
Glioma – less surrouding vasogenic edema
Lymphoma – more homogenous enhancement
Radiation changes / necrosis – within radiation portal
Cerebellar mutism syndrome – post-resection of
posterior fossa tumor, abnormal signal in SCPs
References
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Thank You Very Much For
Reviewing Our Exhibit
Yin.Chen@uphs.upenn.edu
Suyash.Mohan@uphs.upenn.edu