Neuroradiology,holoprosencephaly

1. IMAGING IN
HOLOPROSENCEPHALY AND
RELATED DISORDERS
Presented by:
MD KHALAF
SABA
JR1,RD

2. OVERVIEW
Introduction
Embryology
Epidemiology & Etiology
Severity Scale
Types and its imaging features
•CLASSIC
•VARIANT
•MIMICS
When can the diagnosis be established

3. INTRODUCTION
Holoprosencephaly literally means a single (“holo”) ventricle involving the
embryonic
prosencephalon (“pros”) of the brain (“encephaly”).
They are classified as abnormalities of ventral prosencephalon
development.
Fetal brain fails to bifurcate into two cerebral hemispheres.
DE MYER classified HPE in 2 types
 Classic –
1. Alobar
2. Semilobar
3. lobar
 Variant
1. Middle interhemispheric variant

4. EMBRYOLOGY
Normally the development of brain
starts in 3rd week in utero.
After the completion of primary
neurulation ,the cephalic end of neural
tube forms three primary vesicles
1. Prosencephalon
2. Mesencephalon
3. Rhombencephalon
At around 5 weeks gestation
,prosencephalon cleaves into 2
secondary vesicles
 Telencephalon anteriorly-cerebral
hemispheres, putamen and caudate
nucleus
 Diencephalon posteriorly-thalamus,

5. The prosencephalon develops by the process of ventral induction
which consists of 3 closely interconnected events.
Formation - Aprosencephaly/Atelencephaly
Cleavage - Holoprosencephaly
Midline development - Corpus Callosum agenesis, septo-optic dysplasia, absence of
septum Pellucidum

6. EPIDEMIOLOGY & ETIOLOGY
Considered the most common malformation of the brain and face in
humans.
Prevalence-1 in 10,000 in live and still births
50 per 10,000 in aborted fetuses.
Syndromic HPE:-associated with syndromes like Pallister Hall.
Non syndromic HPE:-Environmental teratogens(e.g-retinoic acid,
alcohol)
Maternal factors –pre pregnancy diabetes, smoking and substance
abuse.

7. Trisomy 13
Trisomy 18
Chromosome 7q deletion
Chromosome 2q deletion
Congenital renal anomalies
Congenital cardiac anomalies
Diabetic embryopathy
Facial anomalies
oAt least 12 regions on 11 separate chromosomes have been identified as playing a role
in familial HPE.
oMutations in 4 main HPE genes (SHH,ZIC2,SIX3,TGIF) are identified in 25% of cases.
Recognised associations include:-

8. SPECTRUM OF SEVERITY
ANENCEPHALY AP/AT
HOLOPROSENCEPHALY
ALOBAR SEMILOBAR LOBAR

9. ANENCEPHALY
Most severe form of cranial neural tube defects .
Characterized by absence of cortical tissue(brain stem and cerebellum may be
variably present) as well as the cranial vault.
Results from failure of closure of the antral end of the neural tube which normally
occurs around 24th day of embryonal life.
Morphological appearance vary from holocrania(most severe) to
merocrania(mildest form).
No parenchymal tissue is seen above the orbits and calvarium is absent.
o“Frog eye” or “mickey mouse” appearance may be seen when seen in coronal plane
due to absent cranial bone,brain and bulging orbits.
oCan be diagnosed on usg as early as 11 weeks.
oBy 14 weeks accuracy approaches to upto 100%.
IMAGING

11. ALOBAR HOLOPROSENCEPHALY
oMost severe form of HPE.
oAbsent interhemispheric fissure with fused
cerebral hemispheres (poorly developed)
oFalx is absent and so are the olfactory bulbs
and tracts.
oOptic nerves –normal ,fused or absent.
oBasal ganglia ,hypothalamic and thalamic nuclei
are typically fused.
oHas a high intrauterine lethality and still birth
rate.
oWith severe facial deformities such as cyclopia
and proboscis , survival is often less than a
week, prognosis of surviving infants is poor.

12. o A CSF filled horse shoe shaped single
mono ventricle continuing posteriorly
with a dorsal cyst.
oThe septum pellucidum,falx cerebri
,interhemispheric fissure and third
ventricle are absent.
oThalami are fused.
oBrain stem and cerebellum appears
relatively normal.
oSingle primitive ventricle and fused
thalami are perhaps the most valuable
US clues for Alobar HPE.
IMAGING
FEATURES

13. SNAKE UNDER THE SKULL
Vascular anomaly seen in
holoprosencephaly.
Occurs due to forward
displacement of anterior
cerebral artery by the
abnormally fused cortical
tissue of 2 frontal lobes.

15. Can have various
configurations
PAN CAKE CUP
BALL

16. DIFFERENTIAL DIAGNOSIS
Major differential of alobar type of HPE is Hydranencephaly.
In hydranencephaly most of the cerebral tissue has been destroyed in
intrauterine life due to some insult /infection.
Face is normal.
Falx is present.

17. SEMI-LOBAR HOLOPROSENCEPHALY
Intermediate in severity between alobar HPE and Lobar HPE.
Most severe SHPE shows a rudimentary interhemispheric fissure and
incomplete falx.
Temporal and occipital horns of the lateral ventricle are partially formed.
Septum pellucidum is absent.
Dorsal cyst is often present.

18. oMost of the interhemispheric fissure appears formed.
oDeep nuclei exihibit various degree of separation.
oBasal ganglia and hypothalami are still largely fused.
oCaudate nuclei appear continuous across the midline.
oA rudimentary third ventricle ,partially separated thalami.
oSplenium of corpus callosum is present but body and genu are absent.
IMAGING FEATURES

19. CT

20. MRI

24. LOBAR HOLOPROSENCEPHALY
Most well differentiated type of HPE.
Interhemispheric fissure and falx are clearly developed,although their most
anterior aspects are shallow and dysplastic.
Third ventricle and lateral ventricle are well formed
Septum pellucidum is absent
Frontal horns are almost always dysmorphic

25. oCerebral hemispheres including thalami and most of the basal ganglia-mostly
separated.
oSome of the most rostral and ventral portions of frontal lobes appear continuous
across midline.
oCaudate head may remain fused.
oFrontal horns of lateral ventricle are present but dysplastic.
oTemporal and occipital horns are better defined.
oThird ventricle appears normal.
oThere is no septum pellucidum.
oCorpus callosum-normal/incomplete/hypoplastic.
oWalls of hypothalamus remains fused and optic chiasm is often smaller .
IMAGING

28. DIFFERENTIAL DIAGNOSIS
Syntelencephaly {middle interhemispheric variant}
Body of corpus callosum is missing and posterior frontal lobes are
continuous across midline.
Septo optic dysplasia
Frontal horns are well formed in SOD.
Arrhinencephaly
Optic bulbs are usually present in lobar HPE.

29. HOLOPROSENCEPHALY VARIANTS

30. SYNTELENCEPHALY
•Also known as Middle interhemispheric variant.
•Anterior and posterior hemispheres are separated by falx and interhemispheric
fissure,mid sections appear fused across midline.
•In contrast to classic HPE,ventral aspects of basal forebrain largely spared ,so basal
ganglia and olfactory sulci appears normal.
•Imaging findings are diagnostic in MIV.
 Corpus callosum splenium and genu present but body is absent.
 Posterior frontal lobes continuous across midline.
 Lateral ventricle bodies appears narrow and fused.

33. SEPTO-PREOPTIC HOLOPROSENCEPHALY
Mild form of HPE.
Failure of hemispheric separation is restricted to subcallosal and/or
preoptic regions.
Patient presents with mild midline cranio facial abnormalities.
Variants include:-
1.Solitary median maxillary central incisor(SMMCI)
2.Congenital nasal pyriform aperture stenosis(CNPAS)

34. SOLITARY MEDIAN MAXILLARY CENTRAL INCISOR SYNDROME
(SMMCI)
•Rare, can have multiple midline abnormalities
•Patient generally present with breathing difficulties.
•Neurodevelopmental delay with hormonal disturbances .
oIsolated dental abnormalities with a single maxillary incisor and v shaped
palate with complex abnormalities involving the brain.
oAnomalies of fornix,septum pellucidum and anterior corpus callosum are
often present.
oAzygous anterior cerebral artery and pituitary stalk hypoplasia often
present.
IMAGING

35. CONGENITAL NASAL PYRIFORM APERTURE STENOSIS
•Can exist as an isolated abnormality.
•Choanal atresia, mid nasal stenosis or aperture stenosis.
•CNPAS can co exist with SMMCI.
•It is associated with hypothalamic pituitary adrenal axis dysfunction.

37. SEPTO OPTIC DYSPLASIA
Well differentiated form of lobar HPE.
Also known as de’morsier syndrome.
Two cardinal pathologic features
 Absence of septum pellucidum
 Optic nerve hypoplasia.
SOD with other anomalies like schizencephaly or callosal dysgenesis syndrome
called as SOD plus.
Mostly sporadic,in some cases mutation of homeobox HESX1 gene is noted.
Most common clinical feature –visual impairment,
Endocrine abnormalities(hypoglycemia,DI),Growth retardation.

39. oThe optic chiasm and one or both optic nerves appear small in about half of the
cases.
oCoronal images show absent or hypoplastic septum pellucidum.
oFrontal horns appear squared off or box like with inferior pointing
IMAGING

40. Saggital images shows absent septum pellucidum, low lying fornix
giving the lateral ventricles an empty appearance.

41. ARRHINENCEPHALY
•Olfactory bulb and tracts are absent.
•Most cases occur with other midline facial anomalies like cleft lip ,cleft palate,
nasal and other ocular abnormalities.
•Olfacory aplasia /hypoplasia associated with hypogonadotrophic hypogonadism-
kallman syndrome.
•Olfactory agenesis occurs in 25% cases of CHARGE syndrome.

42. HOLOPROSENCEPHALY MIMICS

43. HYDRANENCEPHALY
•Severe brain destruction in utero.
•Water without the brain.
•In rare instances,only one hemisphere is involved referred as hemi
hydranencephaly.
•As a result of vascular accident,internal carotid artery circulation gets
compromised before 16th week of gestation followed by liquefactive
necrosis of the cerebrum.
•Most of the cerebral hemisphere is replaced by thin csf filled sac
filling most of the supratentorial space.

44. General features- normal or large head with fluid filled cranial vault (“water bag
brain”) with small remnants of brain parenchyma with normal falx and posterior
fossa.
IMAGING

45. DIFFERENTIAL DIAGNOSIS
ALOBAR HPE
 Falx and interhemispheric fissure is absent and basal ganglia remains fused.
SEVERE OBSTRUCTIVE HYDROCEPHALUS
 A thin cortex can be seen compressed against the dura.
SEVERE CYSTIC ENCEPHALOMALACIA
 Large ventricles with multiple csf filled cavities within the brain.

46. WHEN CAN THE DIAGNOSIS BE ESTABLISHED
•Diagnosis of HPE spectrum can be made prenatally even before 10 weeks of
gestation.
•Commonly it is made between 10-14 weeks on the basis of abnormal
facial morphology and the absence of BUTTERFLY SIGN.
•By the second trimester the diagnosis is made on the basis of features of
HPE as described earlier. (most important-absence of cavum septum
pellucidum.)

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