1. No category

Congenital cranial dysinnervation
disorders (CCDDs)
Cranial Nerve Imaging
in Genetic Disorders:
Dysinnervation and
Deficiency Syndromes
Congenital eye movement disorders
• Abnormal development cranial motor
nuclei & cranial nerves (CNs)
• Failure of target muscle innervation
• Muscle fibrosis (e.g. CFEOM)
Caroline D. Robson, MBChB
Department of Radiology
Division of Neuroradiology
Boston Children’s Hospital
Harvard Medical School
Disclosures and
Acknowledgements
No disclosures pertinent to this presentation
Elizabeth C. Engle, MD
Professor of Neurology and Ophthalmology
Howard Hughes Medical Institute Investigator
FM Kirby Neurobiology Center & the Program in Genomics
Boston Children’s Hospital
Harvard Medical Center
Objectives
• Cranial dysinnervation disorders
• Congenital eye movement disorders
Clinical presentation
Genetic mutations
Imaging features
• Cranial nerve (CN) imaging protocols
• Normal & abnormal CN anatomy
Summary of disorders with defined genetic basis
Non-syndromic Duane
retraction syndrome
(DRS)
Familial DS
CHN1
AD
Type 1 or 3 DS &/or vertical
motility anomalies
Abn CN VI & III
± SOM
hypoplasia
Syndromic DRS
Duane radial ray (Okihiro)
Acro-renal-ocular syn
Townes-Brock syn
SALL4
SALL4
SALL1
AD
AD
AD
DS, radial ray ± HL
DS, radial ray, kidney defects
Imperf anus, HL, thumb malf ±
DS
Hypoplastic/abs
CN VI, aberrant
innerv LRM
HOX mutations
Bosley-Salih-Alorainy syn
Athabascan brain dysgen
HoxB1
HOXA1
HOXA1
HOXB1
AR
AR
AR
Nl EOM, hypo
DS, SNHL, cardiac malf, autism
CN VI, hypo/abs
Horiz gaze restr, SNHL, facial wk ICA, dup VA
Esotropia, CN VII palsy, HL
Absent CN VII
Horizontal gaze palsy w
progressive scoliosis
HGPPS
ROBO3
AR
Horizontal gaze limitation,
scoliosis
Flattened pons
w midline cleft
CFEOM
CFEOM1
KIF21A
AD
CFEOM2
PHOX2A
AR
CFEOM3
TUBB3
AD
Restrictive ophthalmoplegia,
blepharoptosis
Ptosis, restr ophth, exotropia,
poorly reactive pupils
Variable uni/bi bleph,
ophthalmoplegia
Hypo CN III> VI
Hypo LPS, SRM
Hypo EOM,
large LRM abs
CN III & IV
The Congenital Cranial Dysinnervation Disorders (CCDD)
Mendelian
Syndrome
Genetic Locus
Gene & protein function
Oculomotor
Ptosis
CFEOM1
CFEOM3
PTOS1 1p34-p32
FEOM1 12cen
FEOM3 16gter
KIF2A (axon guidance)
TUBB3 (axon guidance)
Trochlear
CFEOM2
FEOM2 11q13
PHOX2A (transcription factor)
Duane
DURS1
DURS2
DRRS
HGPPS
Nucleus
Abducens
DRRS
HGPPS
ABDS/BSAS
8q13
2q31
20q13
11q23
ABDS/BSAS 7p15
CHN1
(axon guidance)
SALL4 (transcription factor)
ROBO3 (axon guidance)
HOXA1 (transcription factor)
From: http://www.childrenshospital.org/research-and-innovation/research/labs/engle-laboratory/neurogenetics-research
1
Congenital eye movement disorders
Abducens defects
Oculomotor, trochlear and abducens nuclei
and nerves
• Duane syndrome
• Horizontal gaze palsy
Oculomotor
Trochlear
Clinical distinction not always possible
Same genetic mutation can cause both
Abducens
Imaging algorithm
Duane syndrome
3T preferred, 32 channel head coil
• Brain screen
Sag T1, Ax T2, FLAIR, DTI
• Orbital imaging (≤ 2 mm, hi res)
Axial T1
Coronal vs quasi coronal T1
•
•
•
•
•
•
•
• Cranial nerve imaging
e.g. esotropia, exotropia, orthophoria
Hi res, small FOV, < 0.5 mm
T2 SPACE vs CISS, etc
Horizontal gaze palsy
•
•
Disorders of abducens development
Lateral rectus
Lateral rectus
Most common of CCDDs
< 5% all strabismus cases, most are sporadic
Limited abduction; variably limited adduction
Globe retraction on attempted adduction
± Additional aberrant eye movements
Types 1 – 3 depending on gaze limitation
Primary gaze deviation
Abducens
Limited abduction and/or adduction
NO globe retraction
Isolated (non-syndromic) DS
•
•
•
•
DS isolated finding ~ 70% cases
Hereditary forms 5 – 10%
Bilateral DS AD
May also affect CN IV & sup div CN III
→ vertical motility deviations
• CHN1 gain of function
Hyperactivates α2-chimaerin → disrupts growth or
guidance of cranial axons destined to innervate
extraocular muscles during development
2
Duane syndrome (type I), left eye
Primary position:
normal
Primary position:
normal
Left abduction:
limited
Left adduction:
globe
retraction
Left adduction:
fissure narrowing
upshoot
Adapted from G.K. von Noorden, Atlas of Strabismus, 1983
3T MR
Abducens nerve
Duane syndrome neuropathology
Hotchkiss et al 80, Miller et al 82
Absence of abducens motor neurons and axons
Aberrant innervation of the lateral rectus by oculomotor nerve
LR (cut)
Abducens
3
Syndromic DS
Duane radial ray (Okihiro)
Acro-renal-ocular syn
Townes-Brock syn
Syndromic DS
SALL4
SALL4
SALL1
AD
AD
AD
• ~ 30% DS + characteristic systemic findings
• AD; loss of function SALL4 mutations
DS, radial ray ± HL
DS, radial ray, kidney defects
Imperf anus, HL, thumb malf ±
DS
Hypoplastic/abs
CN VI, aberrant
innerv LRM
Radial limb anomalies
Hypoplasia thenar eminence to absent forearm
Facial asymmetry
Hearing deficits & ear anomalies
Anal stenosis
Cardiac and renal abnormalities
• HFM occurs in 3% DS patients 22q11.2 del
Syndromic DS
Wildervanck syndrome
HFM (Goldenhar)
Oculoacoustic syndrome
Holt-Oram syndrome
Horizontal gaze palsy
Duane radial ray syndrome
Congenital eye movement disorder
Mutations or deletions in SALL4
Limited primarily to abducens
Oculomotor
Trochlear
•
•
Limited abduction and/or adduction
NO globe retraction
HOX mutations
Bosley-Salih-Alorainy syn
Athabascan brain dysgen
HoxB1
HOXA1
HOXA1
HOXB1
AR
AR
AR
Nl EOM, hypo
DS, SNHL, cardiac malf, autism
CN VI, hypo/abs
Horiz gaze restr, SNHL, facial wk ICA, dup VA
Esotropia, CN VII palsy, HL
Absent CN VII
Horizontal gaze palsy w
progressive scoliosis
HGPPS
ROBO3
AR
Horizontal gaze limitation,
scoliosis
Flattened pons
w midline cleft
HOXA1 syndromes
• DRS/HGP, deafness, vascular anomalies
Right gaze
Left gaze
Middle East (BSAS)
Austism, cardiac defects
American Southwest (ABDS)
Facial weakness, hypoventilation,
intellectual disability
• Autosomal recessive: consanguineous families
• HOXA1 mutation
Encodes transcription factor
Loss of function mutations: absent HOXA1 protein
Tischfield et al, Nature Genetics 2005
4
HGPPS
BSAS & ABDS
Hindbrain patterning
HOXA1
Lateral
Rectus (cut)
• Autosomal recessive
• ROBO3 mutation
• Encodes ROBO3 axon guidance
receptor
• Loss of function mutations
• Absent ROBO3 protein
Abducens
Jen et al, Science 2004
HGPPS
BSAS
ROBO3 mutation
enlarged posterior
communicating arteries
absent internal
carotid arteries
enlarged basilar
artery
ant.
post.
1yo
Horizontal gaze palsy and progressive
scoliosis (HGPPS)
Congenital eye movement disorder
Axonal guidance disorders
Normal 16 yo
HGPPS
HGPPS
Midline crossing of hindbrain axons
ROBO3 - autosomal recessive
Abducens
Remember to monitor for scoliosis in patients with HGP
5
Pontine tegmental cap dysplasia
Oculomotor
nucleus & nerve
Normal
Trochlear nucleus & nerve
Congenital fibrosis of the extraocular muscles
CFEOM
•
•
•
•
Didorders of oculomotor nerve innervation
Oculomotor
Levator (mixed)
Superior rectus (contralateral)
Medial rectus
Congenital, non-progressive
Ophthalmoplegia & ptosis
Neurogenic basis
Three phenotypes: CFEOM 1, 2 & 3
Hypo CN III > VI
AD Restrictive ophthalmoplegia, blepharoptosis Hypo LPS, SR
Eyes infraducted in resting position
Misinnervation LR
Limitation of vertical movements
↓ mean ON size
CFEOM1
KIF21A
Rarely *
CFEOM2
PHOX2A AR Ptosis, restrictive ophthalmoplegia,
exotropia, poorly reactive pupils
CFEOM3
TUBB3 *
AD Variable phenotype: uni/bi blepharoptosis &
ophthalmoplegia, some limitation of vertical
movements
Large LR, hypoplasia
other EOM,
Absent CN III & IV
Variable hypoplasia
SR, MR, LPS & IO
Hypoplasia CN III &
dysinnervation
Congenital fibrosis of the extraocular muscles
CFEOM
•
•
•
•
Congenital, non-progressive
Ophthalmoplegia & ptosis
Neurogenic basis
Three phenotypes: CFEOM 1, 2 & 3
Inferior rectus
Inferior oblique
Clinical: restricted vertical movement or ptosis
6
CFEOM1
Absence of superior division of oculomotor mn / nerve
thin oculomotor nerve
+/- thin abducens nerve
Superior branch oculomotor nerve
CFEOM3
Oculomotor
CFEOM3
CFEOM 1
•
•
•
•
2 yo boy, bilateral congenital ptosis
Pronounced chin up posture
Limited elevation & abduction
Convergence on attempted upgaze
•
•
•
Previously a clinical diagnosis, now genetic
Autosomal dominant
TUBB3 gene mutation (rarely TUBB2B)
Encodes CNS specific beta-tubulin isoform
Special mutations alter microtubule behavior
•
•
Associated findings are mutation dependent
Can be indistinguishable from CFEOM1, however:
Globes infraducted or straight (unlikely to be supraducted)
Ptosis bilateral, unilateral, or absent
Some can elevate above midline
Horizontal position straight to exo - rarely esotropic
Residual eye movements frequently aberrant
Tischfield et al, Cell 2010
Absent CN III & VI
CFEOM3 vs Moebius variant
TUBB 3 mutation
7
Aplasia/hypoplasia CN I, III & VII
Moebius
TUBB3 mutation
Absent CN VII & III
CN IV
• Anisocoria
• Bilateral ptosis, rt exotropia impaired
eye movements
• Facial diplegia
Moebius
Conclusion
• Neurogenic etiology of CCDDS
• Several well-characterized gene
mutations
• Affect development of ocular cranial
motor nuclei and axon guidance to
target muscles
• Illustrated key imaging features that
are characteristic of some of these
disorders
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4/15/2015
Modern Imaging Evaluation of
Visual Loss
Tabby A. Kennedy, MD
University of Wisconsin Department of Radiology
Disclosures
• I have no financial disclosures
Acknowledgements:
Dr. Judy Chen, Ophthalmologist ,UW-Madison
– Visual Field Images
– Funduscopic Images
1
4/15/2015
Objectives
By the end of the presentation, participants
should be able to:
1. Understand the anatomy of the visual
pathway
2. Have a systematic approach to analyzing
images in patients presenting with visual
loss based on clinical history
Visual Pathways
• Complex
choreographed
sensation
• Organization
preserved along the
visual pathway from
the globe to the visual
cortex
hospitalitat.net
2
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Visual Input
http://www.nature.com/nrn/journal
/v8/n4/box/nrn2094_BX1.html
3
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4
4/15/2015
On the retina, image is
flipped & inverted
5
4/15/2015
Visual Pathways
Hofer et al. Front. Neuroanat., 13 April 2010
6
4/15/2015
Making the Diagnosis
Age
Acuity of
Symptoms
Visual Field
Deficit
Clinical
History
Clinical Differential
Diagnosis
Appropriate
Imaging
Make the Diagnosis
ACR Recommendations: Visual Loss
http://www.acr.org
7
4/15/2015
Imaging Protocols: MR Orbit
Pre contrast
T1
PD
T1
T2
T2 FIESTA
Prop DWI
T1
Imaging Protocols: MR Orbit
Pre contrast
T1
PD
T2
T2 FIESTA
T1
T1
T1 Post contrast
8
4/15/2015
Imaging Protocols: MR Brain
T1
T2
DWI
Pre contrast
Post contrast
T1 +C
CUBE FLAIR + C
Cases
9
4/15/2015
Visual Deficits: Defining the Terms
Scotoma: Decrease in visual field
Normal
Macular Degeneration
Cataract
Glaucoma
Diabetic Retinopathy
Visual Deficits and Anatomy
R
L
R
L
Unilateral
Visual Loss
Right
Left
10
4/15/2015
Visual Deficits and Anatomy
Differential Diagnosis
Ocular
Children
• Retinal
Detachment
• Retinoblastoma
• Coats Disease
Adults
•
•
Retinal
Detachment
Mass Lesion
• Melanoma
• Mets
11 yo with Developmental Delay
Retinal Detachment
11
4/15/2015
55 yo with endometrial cancer
T2
CUBE FLAIR
Metastatic Endometrial
Cancer
FIESTA
CUBE FLAIR +C
Visual Deficits and Anatomy
Differential Diagnosis
Optic Nerve
Children
Adults
Congenital
Infection
ON Glioma
Skull Base-mass effect
- Neuroblastoma
- Ewings Sarcoma
- EG
- Fibrous Dysplasia
• Trauma
• Optic Neuritis
• Dura:
Meningioma
• Ischemic Optic
Neuropathy
• Trauma
•
•
•
•
12
4/15/2015
Which Side is Abnormal?
FIESTA
T2
Congenital Optic Nerve
Hypoplasia on the Right
4 Different Patients with Acute
Unilateral Visual Loss
T1 Post contrast
13
4/15/2015
22 yo F with Decreased
Right Monocular Vison
T2
T1 +C
FIESTA
Diffusion
22 yo F with Decreased
Right Monocular Vison
T2
T1 +C
FIESTA
T1 +C
Diffusion
14
4/15/2015
22 yo F with Decreased
Right Monocular Vison
CUBE FLAIR + C
CUBE FLAIR + C
Optic Neuritis
• Visual recovery good
• 48-70% with isolated ON will
have brain lesions consistent
with demyelination
• 56% patients with 1 or more
lesions developed MS vs 22%
with a normal MR
Index Patient
Multiple
Sclerosis
15
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Optic Neuritis
Multiple
Index Patient
Sclerosis
Lumbar Puncture
Sarcoid
Ulcerative
Colitis
Acute Myelogenous Leukemia
(Granulocytic Sarcoma)
22 yo with AML
Presentation
3 Weeks Later
16
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30 yo F with Decrease Monocular vision
in Right Eye over Past 2 days
Right
Left
30 yo F with Decrease Monocular vision
in Right Eye over Past 2 days
R
L
17
4/15/2015
30 yo F with Decrease Monocular vision
in Right Eye over Past 2 days
T2
FLAIR+C
T1 +C
FLAIR+C
FLAIR+C
T1 +C
Multiple Sclerosis
2 yo with Intermittent Esotropia,
Visual Loss
T1 + C
FIESTA
T1 + C
T2
18
4/15/2015
2 yo with Intermittent Esotropia,
Visual Loss
T1 + C
FIESTA
Optic Nerve Glioma, NF1
T1 + C
T2
2 year old with CN 6 palsy and
progressive visual loss
Non Contrast Head CT
19
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2 year old with CN 6 palsy and
progressive visual loss
3D T2
T1 + C
FIESTA
T2
ADC
2 year old with CN 6 palsy and
progressive visual loss
3D T2
FIESTA
Differential Diagnosis
T1 + C
T2
Met Neuroblastoma
Rhabdomyosarcoma
Ewings Sarcoma
EG
Fibrous Dysplasia
20
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2 year old with CN 6 palsy and
progressive visual loss
3D T2
FIESTA
Differential Diagnosis
T1 + C
T2
Met Neuroblastoma
Rhabdomyosarcoma
Ewings Sarcoma
EG
Fibrous Dysplasia
Progressive Right Unilateral Visual
loss; + Optocilliary Shunting
Optic Nerve Sheath Meningioma
21
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Companion Case
Optic Nerve Sheath Meningioma
Visual Deficits and Anatomy
R
L
R
L
Bitemporal
Hemianopia
Right
Left
22
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Visual Deficits and Anatomy
Differential Diagnosis
Chiasm
Children
Adults
• Optic Nerve
• Optic Neuritis
Glioma
• Mass effect
• Mass Effect
• Pituitary/Sella
• Pituitary/Sella
• Meningioma
• Hypothalamus
• Aneurysm
• Third Ventricle
55 year old with decreased vision x 1
year, rapidly progressed over 2 days
Right
Left
23
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55 yo with Bitemporal Hemianopia
Hemorrhagic Macroadenoma
24
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Visual Deficits and Anatomy
R
L
R
L
Homonymous
Hemianopia
Right
Left
Visual Deficits and Anatomy
R
L
R
L
Right
Left
Homonymous
Quadrantopia
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Visual Deficits and Anatomy
Differential Diagnosis
Tract/Radiations
Children and Adults
Stroke
Tumor
Abscess
Demyelinating Disease
(MS/ADEM)
• PRES
• Trauma
•
•
•
•
62 yo with Acute Onset of Complete
Left Homonymous Hemianopia
Right
Left
26
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62 yo with Acute Onset of Complete
Left Homonymous Hemianopia
Acute Right PCA Distribution Infarction
81 yo with visual hallucination,
Right Inferior Quadrantanopia
Right
Left
27
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81 yo with visual hallucination,
Right Inferior Quadrantanopia
Same Patient, 1 month later
Acute Superimposed on Evolved
Subacute Infarction
28
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30 yo Male with Right
Homonymous Hemianopia
Right
Left
30 yo Male with Right
Homonymous Hemianopia
Arteriovenous
Malformation
29
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54 yo with Right
Homonymous Hemianopia
Meningioma
Visual Deficits and Anatomy
R
L
R
L
Right
Left
30
4/15/2015
Objectives
By the end of the presentation, participants
should be able to:
1. Understand the anatomy of the visual
pathway
2. Have a systematic approach to analyzing
images in patients presenting with visual
loss based on clinical history
Modern Imaging Evaluation of
Visual Loss
Tabby A. Kennedy, MD
University of Wisconsin Department of Radiology
I have no disclosures
31
ASNR 2015 Diplopia
Claudia Kirsch M.D.
Associate Professor of Neuroradiology and Otolaryngology
Section Chief of Head and Neck Imaging
Department Radiology Director for Lead, Serve, Inspire Curriculum
Director Radiology Medical Student Teaching
The Wexner Medical Center
The Ohio State University Medical Center
Claudia.Kirsch@osumc.edu
cfekirsch@gmail.com
Diplopia, which means “double vision” comes from the Greek terms, “diplous”
that means “double” and “ops” meaning eye. These symptoms can be distressing to
the patient, and because of the myriad of etiologies and large differential, this can
lead to distress for the diagnosis physician. An ophthalmologist or neurologist
initially sees many patients with diplopia. Importantly, the first distinction is
whether the diplopia is “Monocular” or “Binocular”. In monocular diplopia, the
patient sees double with only one eye open, and the second image often appears as a
ghost, both the patient and physicians can usually breath a sigh of relief, as in
monocular diplopia, the problem is within the eye itself, and may be treated by the
ophthalmologist and the etiologies include refractive problems, wrong glasses, dry
eyes, a warped cornea, or uveitis. (1) However, in “binocular” diplopia the cause
may be life threatening and RED FLAGS should be raised. In these cases the ability
of the neuroradiologist to help determine the cause of binocular diplopia may be
critical for diagnosis and treatment of the patient. (2) Therefore, it is important for
the neuroradiologist to understand the critical anatomy and pathology that can
cause binocular double vision. To this end it is helpful to for neuroradiologist to be
aware of 6 major RED FLAGS –under the mnemonic VISION
V - FIRST RED FLAG - In a patient with a drooping eyelid (ptosis) with a large and
poorly reactive pupil the neuroradiologist is critical in excluding a “Vascular
etiology – i.e. posterior communicating artery, posterior cerebral or superior
cerebellar artery aneurysm. Although elderly patients, diabetics and hypertensive
patients, may present with these findings secondary to vascular ischemic events, in
a patient under 50, a good rule to follow is “A new ptosis is a PCOM, PCA or SCA
aneurysm til proven otherwise”, in elderly patients clinical judgment is necessary,
however an MRA may be easy obtain with the MRA, and help exclude the diagnosis,
the MRI may also help to find strokes, or additional lesions. (1, 2, 3)
I - SECOND RED FLAG- Involvement of more than just diplopia in patients with
diplopia having problems with the eye movement, lid and the pupil (1,2,3), The
neuroradiologist should be on high alert for both a Vascular etiology if there are
these findings with a ptosis and small pupil (miosis) – or Horner syndrome –
looking carefully for a carotid dissection and for Inflammatory etiologies such as
Guillain-Barre or Miller Fisher variants, all of which can be life threatening, or
inflammatory change from demyelination. A good rule of thumb for the
neuroradiologist – if ptosis is combined with other deficits, it’s like a dangerous bag
of potato chips – you can’t have just one - the neuroradiologist should be looking
carefully if there is involvement of other ocular findings with the diplopia. (3)
S - THIRD RED FLAG – Several cranial nerves are involved i.e. CN III, IV and VI in
the diplopia, suggestive of a cavernous sinus lesion, or any adjacent nerves including
the V1 and V2 divisions of the trigeminal nerve, or checking the pons and Skull base
if the Seventh CN (CN VII) is involved. (3) In addition S – stands for Skull base or
Sphenoid near the Superior Orbital fissure fractures - a fracture along the
course skull base, may affect CN VI which is close to the floor of the posterior cranial
fossa, fractures involving the sphenoid or superior orbital fissure may affect all of
the nerves extending through including CN III, CN IV, CN IV or V1. (2)
I –FOURTH RED FLAG – Infection – especially severe sinus infections, that may lead
to cavernous sinus involvement, or infections leading to a meningitis, these patients
should be imaged and assessed carefully. In addition an important I – the
neuroradiologist should be on the lookout for is Increased Intracranial Pressure –
CN VI palsy may occur from the nerve being compressed along the petrous temporal
ridge, or CN III with a blown pupil. (1, 2,3,4,)
O – FIFTH RED FLAG - Onset of new headache, i.e. worst headache of life, for
subarachnoid hemorrhage or new headache with scalp tenderness or pain with
chewing, these findings can be seen with Giant cell arteritis, which if the
neuroradiologists looks carefully for along the superficial temporal artery, may help
in aiding in the diagnosis. (1,2,3)
N – SIXTH RED FLAG – Neoplasm, patients with history of tumors that may be
either primary in neurofibromatosis with schwannomas along the nerve, or
metastatic with leptomeningeal disease, or skull base invasion, these patients also
need to be imaged with careful attention to the course of the cranial nerves CN IIIVII. Neoplasms in the region of the fourth ventricle can also compress CN VI, often
this occurs in conjunction with its neighbor CN VI, resulting both in a diplopia with
paralysis of lateral gaze and an ipsilateral paralysis of the muscles of facial
expression. (1,2,3)
To better understand the causes of binocular diplopia, the neuroradiologist
should be aware of the anatomy and pathology that can lead to this disorder. This
includes understanding the course of the cranial nerves, (CN) CN III, CN iV, and CN
VI, as well as important contributions from the neighboring CNs II, V and VII, and
the imaging features of pathology than disrupt these nerves leading to double vision,
at either the level of the brain stem, subarachnoid space, cavernous sinus, superior
orbital fissure and orbit. Lastly, the control of eye movements by the upper motor
neurons coordinates the eye movements and these combinations are briefly
reviewed at the end. (5)
The first cranial nerve reviewed is CN III – or the oculomotor nerve.
The oculomotor nerve is both a somatic motor nerve with efferent fibers supplying
the levator palpebrae superioris, superior, inferior, medial and lateral rectus and
inferior oblique muscles of the orbit, and a visceral motor efferent with
parasympathetic supply to constrict the pupil and ciliary muscles, via the ciliary
ganglion. (3)
The CN III nucleus somatic motor component is “V” shaped and is located in
the midbrain at the level of the superior colliculus, just anterior to the cerebral
aqueduct, with the medial longitudinal fasiculus as its neighbor laterally and
inferiorly. In the brainstem, the oculomotor complex is composed of Lateral
subnuclei with the dorsal component supplying the ipsilateral inferior rectus, the
intermediate nucleus the inferior oblique, and ventral nuclei supplying the medial
rectus muscles. The Medial subnucleus gives supply to the contralateral superior
rectus, and the Central subnucleus gives supply to the bilateral levator palpebrae
superiorus muscles, with the Edinger-Westphal (visceral motor) nucleus located
posteriorly, which gives rise to the parasympathetic fibers. The somatic motor
fibers and parasympathetic fibers form the CN III Oculomotor nerve.
The CN III axons for the lower motor neurons go anteriorly through midbrain
tegmentum, through the red nucleus and emerging in the medial interpeduncular
cistern where the pons and midbrain merge. CN III runs between the superior
cerebellar artery and posterior cerebral artery, just below the posterior
communicating artery. CN III then goes through the dura into the cavernous sinus,
running along the superior lateral wall above the trochlear nerve. The nerve exits
via the superior orbital fissure, into the tendinous ring, and upon entering the orbit
divides into superior and inferior components. The superior nerve of CN III goes
superiorly and lateral to the optic nerve supplying the superior rectus and levator
palpebrae. The inferior CN III splits into 3 parts, supplying the inferior rectus, and
medial rectus muscles along the medial ocular margin and the inferior oblique along
the back posterior margin of the muscle. (3)
The Edinger-Westphal visceral motor neurons course along with the somatic
motor axons, from the middle cranial fossa, cavernous sinus and superior orbital
fissure. The nerves separate from the nerve supplying the inferior oblique muscle
and end up in the ciliary ganglion located near the apex of the orbital cone. Exiting
from the ciliary ganglion are short ciliary nerves that join with sympathetic fibers
from the ICA, these enter into the globe at the posterior margin near the optic nerve.
These nerves that control the constrictor pupillae muscles and ciliary muscles, run
in between the sclera and choroid of the eye ending up in the ciliary body and iris of
the globe. Thus these fibers control pupil size and lens shape.
Critical anatomic sites that can lead to diplopia starting along the course of
the nerve include a stroke of the basal midbrain, this diplopia is usually associated
with other symptoms including a contralateral hemiplegia due to the adjacent
corticospinal tract fibers, or if in the red nucleus and ipsilateral ophthalmoplegia
and contralateral intentional tremor. (3)
As the nerve cross from the midbrain to the cavernous sinus, an aneurysm
from either the Posterior communicating artery, Posterior cerebral artery or
Superior Cerebellar Artery and cause a ptosis by denervation of the levator
palpebrae superiorus and continued action of cranial nerve VII on the orbicularis
oculi. In addition if there is any inflammatory or leptomeningeal process this can
affect the nerve, and temporal lobe uncal herniation will displace the cerebral
peduncle to the contralateral side, displacing and distorting CNIII along the tentorial
notch. As the nerve extends through the cavernous sinus, pathological conditions
in this region may also affect the nerve, with the neuroradiologist paying attention
to the etiologies listed under the VISION RED FLAGS.
CN IV, the trochlear nerve is smallest cranial nerve, with the largest
intracranial course, and is a somatic motor nerve that only innervates the superior
oblique muscle, with the nucleus located in the midbrain tegmentum below CN III, in
the inferior colliculus. Most motor neurons are located medially as is the nucleus,
which is also just ventral to the cerebral aqueduct. The course is unique as it is the
only nerve that exits from the back (dorsal) part of the brain stem, and then crosses
to the opposite side, therefore the superior oblique is innervated by the trochlear
nucleus located in the contralateral brainstem. CN IV runs with CN III between the
PCA and SCA arteries, along the margin of the free and attached margin of the
tentorium cerebelli, the nerve runs below CN III in the cavernous sinus, and through
the superior orbital fissure crossing diagonally across the levator palpebrae and
superior rectus muscle to the superior oblique muscle. The nerve can be affected by
all of the same etiologies as CN VII, discussed earlier. When the CN IV is notfunctioning the CN III and CN VI take over the globe, which is rotated outwardly by
abduction from CN VI and inferiorly from unopposed action of the muscles
innervated by CN III. (3)
CN VI, the abducens nerve is also a somatic efferent nerve to the lateral
rectus muscle whose nucleus is located in the pontine tegmentum, and like the
additional somatic motor nuclei it is located closer to the midline just anterior to the
fourth ventricle, as the seventh nerve circles over the sixth nerve it creates a little
hill “colliculus” along the fourth ventricular floor. The CN VI emerges where the
pons and medullary pyramid meet, and extends through the prepontine cistern
entering the dura lateral to the dorsum sella, within this region it travels through
Dorello’s canal over the apex of the petrous portion of the temporal bone. After
taking this turn CN VI extends into the cavernous sinus, the most medial of the
cranial nerves, next to the internal carotid artery, and then extends into the superior
orbital fissure. In patients who have a lower motor neuronal lesion, the lateral
rectus muscle is denervated and the patient cannot abduct the globe laterally, and
the globe is pulled medially due to the unopposed action of CN III on the medial
rectus muscle. Again, as in the VISION mnemonic, the neuroradiologist should be on
the lookout for a Vascular aneurysm looking also at the basilar and posterior
inferior cerebellar arteries or abnormal increased attenuation within the basilar
artery (thrombus) that may occlude the pontine branches resulting in a pontine
infarct. Inflammatory changes along the nerve may also affect the nerve and result
in diplopia. (3)
The complex coordination of vision is controlled by several key centers;
briefly these include the Paramedian pontine reticular formation (PPRF)
coordinating CN III and CN VI via ascending fibers of the medical longitudinal
fasiculus (MLF) for Lateral Gaze. Pontine infarcts, can affect this region, resulting in
paralysis of conjugate lateral gaze. Lesions along the MLF can result also in a
problem with lateral gaze and a nystagmus because of vestibule-oculomotor fibers.
(5)
Neurons projecting between CN III in the oculomotor subnuclei and CN IV
control Vertical Gaze. Tumors in the pineal region can extend to the superior
colliculus to the Vertical Gaze center and cause a paralysis of upward gaze or
Perinaud syndrome. (1)
REFERENCES:
1. Evaluation of Diplopia: An Anatomic and Systematic Approach. Pelak S. V,
Hospital Physician, March 2004. P. 16-24
2. Deciphering Diplopia: Eyenet. Karmel M. Nov.-Dec.-2009, p. 31-34
3. Sandoz Course: Cranial Nerves, Anatomy and Clinical Comments, Wilson –
Pauwels, Akesson, Stewart. Mosby & Co. 1988.
4. Neuroimaging and Acute Ocular Moto Mononeuropathies: A Prospective Study,
Murchison AP, Gilbert ME, Savino PJ, Archives of Ophthalmology Vol. 129: 3, March
2011, p, 301 – 305
5. Brainstem Pathways for Horizontal Eye Movement: Pathologic Correlation with
MR Imaging .Bae YJ, Kim H, Choi BS, et al. Radiographics 2013; 33:47-59.