- Holoprosencephaly is a rare brain malformation caused by incomplete separation of the brain hemispheres. It can range from mild to severe forms depending on the degree of separation, and is classified as alobar, semilobar, or lobar. Related disorders include septo-optic dysplasia, syntelencephaly, and arhinencephaly. Hydranencephaly, where most of the brain is replaced by cerebrospinal fluid, is an important mimic. Prenatal diagnosis is possible as early as 6 weeks and involves looking for abnormal facial features and absence of the cavum septum pellucidum.
Description of various ultrasound features of benign and suspicious thyroid nodules with multiple ultrasound systems for risk stratification of malignancy.
FETAL CENTRAL NERVOUS SYSTEM ANAOMALIES PRESENTATIONkumarramalakshmi
various fetal cns anamolies described with ante nantal and postnatal imaging features of ultrasound, barium study CT and MRI in each entity with representative iamges
Description of various ultrasound features of benign and suspicious thyroid nodules with multiple ultrasound systems for risk stratification of malignancy.
FETAL CENTRAL NERVOUS SYSTEM ANAOMALIES PRESENTATIONkumarramalakshmi
various fetal cns anamolies described with ante nantal and postnatal imaging features of ultrasound, barium study CT and MRI in each entity with representative iamges
It's about HYDROCEPHALUS
TO EXPLAIN ANATOMY OF HUMAN BRAIN
TO INTRODUCE HYDROCEPHALUS
TO DEFINE HYDROCEPHALUS
TO EXPLAIN INCIDENCE OF HYDROCEPHALUS
TO EXPLAIN ETIOLOGY OF HYDROCEPHALUS
TO EXPLAIN PATHOPHYSIOLOGY OF HYDROCEPHALUS
TO EXPLAIN CLINICAL MANIFESTATION OF HYDROCEPHALUS
TO ENLIST DIAGNOSIS & DIAGNOSTIC EVALUATION FOR HYDROCEPHALUS
TO DESCRIBE MANAGEMENT OF HYDROCEPHALUS
TO EXPLAIN COMPLICATION & PROGNOSIS OF HYDROCEPHALUS
Error of Dorsal Induction
Results in defect of closure of neural tube which leads to various anomalies like anencephaly, encephalocoele, spinal dysraphism and chiari malformations.
The blood supply to the central nervous system (CNS), including the brain and spinal cord, is crucial for maintaining the metabolic needs of neural tissues.
Neurosurgical interventions related to the blood supply of the CNS are often aimed at addressing vascular abnormalities, preventing strokes, and managing conditions affecting blood vessels in the brain.
Cavernous Sinus Thrombosis.
Artficial Intelligence in Health universities(JSS) Vikram Patil
Artificial intelligence (AI) is a growing phenomenon
Will soon facilitate wide-scale changes in Health education and Healthcare delivery.
Students and Educators need to have the knowledge of AI in relation to learning and research
They need to know extent to which it will impact on education and healthcare delivery
The ppt is useful to understand the role of Universities in the era of AI
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
5. CLASSIC
• Alobar HPE.
• Semilobar HPE.
• Lobar HPE.
• The distinction between these 3 forms is
based primarily on the presence or absence of
a midline fissure separating the hemispheres.
6. ALOBAR HPE
• Most severe.
• No midline fissure, no identifiable lobes.
• Fused basal ganglia.
• Agyric /disordered gyri /shallow sulci.
• Single crescent monoventricle - opening dorsally into
a large CSF filled dorsal cyst.
7. ALOBAR HPE
Small rim of cortex surrounds "horseshoe"
central monoventricle. Thalami are fused.
More cephalad scan in the same patient shows
a large dorsal cyst and central monoventricle
with thin rim of surrounding brain.
8. SEMILOBAR HPE
• Intermediate form.
• Primitive ventricular horns, third ventricle.
• Fused basal ganglia&hypothalami, thalami often separated.
• Rudimentary falx, posterior IHF.
• Posterior CC forms while anterior aspects are absent.
9. SEMILOBAR HPE
H-shaped central ventricle with primitive-
appearing temporal horns, fused basal ganglia,
and rudimentary interhemispheric fissure.
Axial T2WI - Rudimentary posterior
interhemispheric fissure, primitive
ventricular horns, and
anterior midline fusion.
10. SEMILOBAR HPE
Sagittal T1WI shows sHPE with
partial differentiation of third
ventricle, occipital horns.
Axial T2WI in the same patient-
Rudimentary temporal and
occipital horns. The third ventricle
is partially formed. The thalami are
separated, but the hypothalamus
remains fused.
11. SEMILOBAR HPE
More cephalad T2WI in the same patient shows
fused basal ganglia, rudimentary posterior
interhemispheric fissure, and absence of
anterior interhemispheric fissure with the brain
fused across the midline.
More cephalad scan shows the
upper aspect of a poorly
differentiated central monoventricle
12. LOBAR HPE
• Best-differentiated.
• IHF & Falx are clearly developed, with shallow and
dysplastic-appearing anterior aspects.
• Third & lateral ventricles – well formed.
• Cavum septum pellucidum is always absent.
• Rudimentary frontal horns are typical , and only the most
inferior portions of the frontal lobes are fused.
13. LOBAR HPE
Sagittal T2WI of lobar HPE
shows well-differentiated
brain, nearly normal-appearing
third ventricle & azygous ACA
Axial T2WI shows well-
developed occipital horns,
third ventricle, and
minimal anterior midline
fusion.
Coronal T2WI shows that the
anteroinferior frontal cortex is
fused across the midline.
14. VARIANTS
• Syntelencephaly aka middle interhemispheric
variant of HPE.
• Septopreoptic HPE
- Solitary median maxillary central incisor syndrome.
- Congenital nasal pyriform aperture stenosis.
15. SYNTELENCEPHALY
• CC genu, splenium present, middle absent.
(Only brain malformation with that morphology)
• Mid-sections of falx, interhemispheric fissure
absent.
• Posterior frontal gray/white matter fused across
midline.
16. SYNTELENCEPHALY
Axial graphic-Absent midsection of the IHF,
upward extension of an anomalous sylvian
fissure across the midline and foci of both gray
& white matter that bridge the hemispheres.
Axial NECT- Midportions of
the hemispheres appear fused
across the midline with bridges
of both white and gray matter.
17. SYNTELENCEPHALY
Corpus callosum genu and splenium are
present without an intervening body.
Note dysplastic gray matter deforming
the lateral ventricle.
Coronal T2- fused,"notched" lateral
ventricles with a nodule of gray
matter perched on top of the fused
lateral ventricle.
18. SOLITARY MEDIAN MAXILLARY
CENTRAL INCISOR SYNDROME.
• Single midline incisor.
• Often coexists with nasal anomalies.
• Brain anomalies of fornix, septi pellucidi, CC.
common.
19. SMMCI
Axial bone CT in a 3d infant with
breathing difficulty shows a single
midline maxillary incisor.
Coronal bone CT in the same patient
shows the central incisor and
narrowed pyriform aperture stenosis.
20. SMMCI
Axial T2WI in the same patient at age 7
months shows lobar HPE with mild
hypotelorism and fusion across the
ventral frontal lobes.
More cephalad scan shows absent
septi pellucidi and thickened
dysplastic-appearing fused fornices.
23. RELATED MIDLINE DISORDERS
• Septooptic dysplasia.
- SOD plus – associated with other
anomalies ( Schizencephaly / callosal agenesis)
• Arrhinencephaly.
24. SEPTOOPTIC DYSPLASIA
• Aka De Morsier syndrome.
• Absence of septi pellucidi.
- Squared-off frontal horns, pointed
inferiorly on coronal T2WI
• Hypoplastic optic nerves, chiasm.
• Look for
○ Malformations of cortical development
○ Thin stalk, small gland, ectopic posterior pituitary
25. SEPTOOPTIC DYSPLASIA
Absent cavum septi pellucidi
with flat-roofed anterior
horns and small optic chiasm.
Cavum septi pellucidi are
absent ; boxlike lateral
ventricles with inferiorly
pointed frontal horns.
Coronal T2WI in newborn-
absent cavum septi pellucidi,
schizencephaly,extensive
polymicrogyria, fused
fornices.
26. SEPTOOPTIC DYSPLASIA
Empty-appearing lateral ventricle with
low-lying fornix. The optic chiasm
appears small.
Hypoplastic optic chiasm, absent septi
pellucidi & the peculiar box-like or squared-
off" appearance of the frontal horns.
27. SEPTOOPTIC DYSPLASIA
Extreme hypoplasia of the optic chiasm,
small pituitary gland with inapparent stalk,
and low-lying fornices that give a striking
"empty“ appearance to the lateral ventricle.
Coronal IR in the same case- unilateral
schizencephaly with dysplastic gray
matter lining the cleft. Note contralateral
polymicrogyria.
28. ARRHINENCEPHALY
• Absent olfactory bulb and tracts.
• Often seen in association with other midline
facial abnormalities (cleft lip/palate,…)
• Kallman syndrome.
• CHARGE syndrome – in 25% with olfactory
agenesis.
30. MIMICS
• HYDRANENCEPHALY
- Consequence of severe brain destruction in utero.
- “Water bag" brain.
- Small nubbins of remnant brain with a normal falx
cerebri and posterior fossa.
- Hemihydranencephaly.
31. HYDRANENCEPHALY
Large head with striking
transillumination indicating that most
of the cranium is water-filled.
The hemispheres are absent ("water-bag
brain"), and only the basal ganglia are
present. Note separation.
32. HYDRANENCEPHALY
A falx cerebri and tentorium are
present, as are the separated basal
ganglia. The hemispheres are absent.
Both hemispheres are replaced
by CSF. BG/thalami are separated,
falx is present. No brain is visible
over CSF-filled cavities.
33. HYDRANENCEPHALY
Sagittal T1WI - hydranencephaly
with macrocephaly; CSF fills virtually
all of the supratentorial spaces.
Coronal T1WI in the same case-
expanded, CSF-filled cranial vault, only
tiny remnants of brain. A falx is present.
34. D/D
• Severe obstructive hydrocephalus (OH)
Sagittal T1–massively enlarged lateral ventricles
& tectal dysplasia causing aqueductal stenosis.
Thin rim of compressed but normally formed
cortex and subcortical WM lying under the
calvarium.
35. D/D
• Alobar holoprosencephaly
Almost the entire calvarium is occupied by the
CSF-filled monoventricle covered by a very thin
rim of featureless brain.
The basal ganglia are fused. Note
absent falx, thin rim of smooth
dysplastic appearing brain.
36. D/D
• Severe bilateral "open lip" schizencephaly
Axial T2WI- Severe "open lip"
schizencephaly, another cause of
"water-bag brain" appearance.
Coronal T2WI- falx and tentorium are normal.
The massive "open lip" schizencephalic clefts
are lined by dysplastic-appearing gray matter.
37. PRENATAL DIAGNOSIS
• As early as 6 weeks from the LMP.
• 10 - 14 weeks -- abnormal facial morphology
and absence of the “butterfly” sign.
• Early closure of the metopic suture.
• Absence of the cavum septum pellucidum –
Hallmark.
38. BUTTERFLY SIGN
• Normal appearance of the choroid plexuses
on axial imaging of the normal first-trimester
brain.
39. SUMMARY
• Incomplete separation of the two hemispheres.
• Types - Classic – Alobar, Semilobar, Lobar.
D/D – Hydranencephaly.
D/D – Alobar/ Lobar HPE,
depending on severity of sHPE.
D/D - SOD,Arrhinencephaly ,
Syntelencephaly
43. CONCLUSION
• HPE is not uniformly lethal, as is commonly
thought.
• Survival depends on the severity of the brain
and facial malformations, the presence of
chromosomal abnormalities, the involvement
of other organs, and the presence of a
multiple anomaly syndrome.
44. REFERENCES
• Osborn’s Brain Imaging, Pathology, and
anatomy – Second edition.
• Holoprosencephaly: A Survey of the Entity,
with Embryology and Fetal Imaging - Thomas
C. Winter , Anne M. Kennedy, Paula J.
Woodward.
• Holoprosencephaly: A Guide to Diagnosis and
Clinical Management - Manu S Raam,
Benjamin D Solomon and Maximilian Muenke.
In the earliest stages, bilateral outpouchings from the neural tube initially form a single central fluidfilled
cavity (“monoventricle”) that will eventually develop into the lateral and third ventricles (see Chapter 34).
The separation into two hemispheres is normally completed by the fifth gestational week.
The embryonic ventricular system is a series of interconnected fluid-filled chambers that arise as expansions from
the central cavity of the embryonic neural tube. As the developing brain bends and expands, it forms fore-brain,
midbrain, and hindbrain vesicles. The forebrain cavity divides into two lateral ventricles, which develop as
outpouchings from the rostral third ventricle and are connected to it by the interventricular foramen (foramen of
Monro) (34-1).
The cerebral aqueduct develops from the midbrain vesicle. The fourth ventricle develops from the hindbrain cavity
and merges proximally with the aqueduct and caudally with the central canal of the spinal cord
The holoprosencephalies are characterized by failure of normal dorsal-ventral induction and lack of rostral
forebrain cleavage. In the most severe forms, diencephalic-derived structures such as the basal ganglia also remain
fused in the midline. As ventral induction is closely related to facial development, HPE is also associated with a
number of characteristic facial anomalies.
The eye field begins as a single midline structure. Under the signaling influence of the prechordal plate, the eye field in vertebrates splits into separate left and right eyes. If this developmental process is not completed correctly, the result is cyclopia
Probst- presence or absence of a dorsal sac and cleavage of basal structures are used to categorize the process in children
“minimal” HPE, which is associated with subtle craniofacial malformations and mild developmental delay; and microform HPE, which by definition excludes brain involvement.
(a) synophthalmia and a proboscis in a patient with alobar holoprosencephaly; (b) severe hypotelorism, flat nasal bridge, bilateral colobomas, and midline cleft lip and palate in a patient with alobar holoprosencephaly; (c) hypotelorism, flat nasal bridge, and closely spaced nostrils in a patient with lobar holoprosencephaly; (d) hypotelorism, sharp nasal bridge, and single maxillary central incisor in an individual with a microform of holoprosencephaly
The most severe facial malformations are seen in association with alobar HPE.
The presence of a dorsal cyst strongly correlates with thalamic fusion, hence the high frequency with alobar HPE. It is thought that the flow of cerebrospinal fluid out of the third ventricle is obstructed by fusion of the thalami, and, as a result, the third ventricle balloons out posteriorly at the point of least resistance in the suprapineal recess.
The single primitive ventricle and fused thalami are perhaps the two most valuable US clues for alobar HPE. Important differential diagnostic considerations for alobar HPE, such as hydranencephaly and severe hydrocephalus (42), exhibit normal thalamic cleavage and usually at least a partially visualized falx cerebri.
Hydranencephaly – Face normal, Falx +, Most of cerebral tissue has been destroyed, usually by intrauterine vascular accident or infection.
varying degrees of separation of the deep nuclei. When thalamic fusion is present, there may be a dorsal cyst in semilobar HPE
The farther anterior the cc forms, the better the brain is developed.
IH fissure- rudimentary in most severe forms, forms in better-differentiated shpe.
Coronal autopsy case of severe semilobar HPE shows Hshaped central ventricle with primitive-appearing temporal horns , fused basal ganglia ſt, and rudimentary interhemispheric fissure.
Axial T2WI shows severe sHPE with rudimentary posterior interhemispheric fissure st, primitive ventricular horns ſt, and anterior midline fusion. Diffuse frontal migration arrest with
subcortical heterotopic GM is also present.
Sagittal T1WI shows sHPE with partial differentiation of third ventricle , occipital horns . The midbrain, pons, and cerebellum are comparatively normal.(38-8B) Axial T2WI in the same patient shows mild hypotelorism with no other midface anomalies. Rudimentary temporal ſt and occipital st horns are present. The third ventricle is partially formed. The thalami
are separated, but the hypothalamus remains fused.
More cephalad T2WI in the same patient shows fused basal ganglia ſt, rudimentary posterior interhemispheric fissure st, and absence of anterior interhemispheric fissure with the brain
fused across the midline . (38-8D) More cephalad scan shows the upper aspect of a poorly differentiated central monoventricle. The corpus callosum and all normal midline structures
are absent.
Sagittal T2WI of lobar HPE shows well-differentiated brain, nearly normal-appearing third ventricle , and azygous ACA ſt.
Coronal T2WI shows that the anteroinferior frontal cortex is fused across the midline st.
Axial T2WI shows well-developed occipital horns ſt, third ventricle , and minimal anterior midline fusion st.
Mih – inbetween semilobar and lobar in terms of severity.
Axial graphic depicts syntelencephaly with absent midsection of the interhemispheric fissure, upward extension of an anomalous sylvian fissure across the midline , and foci of both gray
and white matter that bridge the hemispheres. (38-11A) Axial NECT scan in a patient with syntelencephaly shows that the midportions of the hemispheres appear fused across the midline with bridges of both white ſt and gray matter .
Sagittal T1WI shows classic findings of MIH. Corpus callosum genu ſt and splenium are present without an intervening body. Note dysplastic gray matter st deforming the lateral ventricle. (38-11C)
Coronal T2 shows fused, "notched" lateral ventricles ſt with a nodule of gray matter perched on top of the fused lateral ventricle. The posterior frontal lobes are continuous
across the midline st without an interhemispheric fissure.
Axial bone CT in a 3d infant with breathing difficulty shows a single midline maxillary incisor ſt. (38-12B) Coronal bone CT in the same patient shows the central incisor ſt and narrowed pyriform aperture stenosis . In the term newborn, the normal aperture width should be > 8 mm.
Axial T2WI in the same patient at age 7 months shows lobar HPE with mild hypotelorism and fusion across the ventral frontal lobes ſt. (38-12D) More cephalad scan shows absent septi
pellucidi and thickened dysplastic-appearing fused fornices ſt.
(A) Patient with alobar HPE. (A1) Note cyclopia with doubling of eye structures, arrhinia, rudimentary proboscis and agnathia. (A2) microcephaly and malformed ears. (B) Patient with alobar HPE note premaxillary agenesis and hypertelorism. (C) Patient with semilobar HPE. (C1) Note hypotelorism, squint and cleft lip. (C2) Microcephaly, brachycephaly and large ears. (D) Patient with semilobar HPE showing hypotelorism. (E), (F) and (G) are patients with semilobar HPE showing hypertelorism. (H) Patient with semilobar HPE and Dandy Walker malformation showing normal facial features except for ear asymmetry (simple right ear). (I1) Patient with MIH having hypertelorism and (I2) occipital cephalocele
Coronal graphic shows SOD with absent cavum septi pellucidi with flat-roofed anterior horns and small optic chiasm ſt.
Coronal T2WI in newborn shows absent cavum septi pellucidi , schizencephaly ſt, extensive polymicrogyria , fused fornices .
Cavum septi pellucidi are absent ; boxlike lateral ventricles with inferiorly pointed frontal horns are seen.
Sagittal T2WI in a 13m boy with septooptic dysplasia (SOD) shows an empty-appearing lateral ventricle with low-lying fornix . The optic chiasm appears small.
Coronal T2WI shows the hypoplastic optic chiasm , absent septi pellucidi , and the peculiar box-like or "squared-off" appearance of the frontal horns. The inferior pointing ſt of both frontal horns is also characteristic of SOD.
Sagittal T1WI in a 26y woman with SOD shows extreme hypoplasia f the optic chiasm ſt, small pituitary gland with inapparent stalk st, and low-lying fornices that give a striking "empty"
appearance to the lateral ventricle .
Coronal IR in the same case shows unilateral schizencephaly with dysplastic gray matter lining the cleft st. Note contralateral polymicrogyria ſt.
Coronal T2WI in a normal newborn shows olfactory bulbs ſt and normal olfactory sulci
Coronal T2WI in a newborn with multiple congenital anomalies demonstrates arrhinencephaly with absent olfactory bulbs ſt and no olfactory sulci .
A normal or large head with fluid-filled cranial vault.
Compromise of the internal carotid artery circulation before 16 gestational weeks followed by diffuse liquefactive necrosis of the cerebral mantle is responsible.
In hydranencephaly, most of the cerebral hemispheres have been destroyed and are totally or partially replaced by translucent thin-walled sacs of CSF that fill most of the supratentorial space.The outer layer consists of leptomeninges, and the inner layer is glial tissue without demonstrable ependymal elements.
Autopsy case of hydranencephaly demonstrates a large head with striking transillumination indicating that most of the cranium is water-filled.
The thinned calvarium has been partially removed to show the fluid-filled cavity. The hemispheres are absent ("water-bag brain"), and only the basal ganglia are present. Note separation
This is the same case as Figure 38-22, seen from above. A falx cerebri and tentorium are present, as are the separated basal ganglia . The hemispheres are absent. NECT shows
hydranencephaly. Both hemispheres are replaced by CSF. BG/thalami are separated , falx is present ſt. No brain is visible over CSF-filled cavities st.
Sagittal T1WI shows hydranencephaly with macrocephaly; CSF fills virtually all of the supratentorial spaces. Brainstem and cerebellum are normal.
Coronal T1WI in the same case shows expanded, CSF-filled cranial vault, only tiny remnants of brain ſt. A falx is present.
- thin cortex can be seen compressed against the dura and inner table of the calvaria.
Sagittal T1WI in a 4-week infant with macrocrania shows massively enlarged lateral ventricles and tectal dysplasia ſtcausing aqueductal stenosis .
Coronal T2WI shows the massively enlarged lateral ventricles . There is a thin rim of compressed but normally formed cortex ſt and subcortical WM lying under the calvarium. This is maximal hydrocephalus.
This is alobar holoprosencephaly. Sagittal T2WI shows enlarged head with relatively normal appearing posterior fossa. Almost the entire calvarium is occupied by the CSF-filled monoventricle covered by a very thin rim of featureless brain .
Coronal T2WI shows a horseshoe-shaped monoventricle. The basal ganglia are fused. Note absent falx, thin rim of smooth dysplastic appearing brain .
Axial T2WI shows severe "open lip“ schizencephaly, another cause of "water-bag brain" appearance.
Coronal T2WI in the same case shows that the falx and tentorium are normal. The massive "open lip" schizencephalic clefts are lined by dysplastic-appearing gray matter.
3. height of the frontal bones at the suture was higher.
4. If the face is normal, inability to demonstrate a normal cavum septum pellucidum may be the only hint that there is severe brain malformation -- careful follow-up is essential with endovaginal US, three-dimensional volume acquisition, and fetal MR imaging.
Normal skull and brain at 13 weeks. Axial view of the head showing the normal calcification of the skull; the falx and the two choroid plexuses ("butterfly sign") are normal. (b) Alobar holoprosencephaly: transverse view of the head showing the fusion of the thalami and of the lateral ventricles.
Inability to demonstrate this sign within a normal cranial vault is highly suggestive of HPE
Among euploid patients with HPE, there is an inverse relationship between the severity of the facial phenotype and the duration of survival.
In fetuses with HPE, look for additional anomalies, consider fetal MR imaging, offer karyotype with microarray analysis.
