Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
DEVELOPMENTAL
NEUROPATHOLOGY OF CORTICAL
DYSPLASIA
Amanda Rivera-Begeman D.O.
Perinatal and Pediatric Pathologist
Dell Chi...
Goals of this lecture
•Brain development
•Neuronal migration, cortical development
•Cortical dysplasia and clinical correl...
Brain development - Overview
Neurulation (3-4 weeks) Cerebral vesicle formation (4-7 weeks)
Corticogenesis (8-16 weeks) Ma...
Neurulation: weeks 3-4 of embryonic
development
Cerebral vesicle formation, AKA
‘regionalization’ (4-7 weeks) gestation
Unknown author of diagram, retrieved from internet
Corticogenesis: neural cell migration leads to
Cortical plate formation (8-16 wks)
Telencephalic
wall
Illustration by Lydi...
Neural development
Induced by exogenous cues
from the microenvironment
*
Unknown author of diagram, retrieved from internet
Neuronal migration
Inner surface
Outer surface
Telencephalic
wall
Bear, M., Connors, B., & Paradiso, M. (2007). Neuroscien...
External layer/marginal zone
Cortical plate
Subcortical plate/external
Intermediate zone
Intermediate zone/subventricular
...
neocortex
Molecular layer
External granular layer
External pyramidal layer
Internal granular layer
Internal pyramidal laye...
Gyral development
• Convolutions occur because the cortical surface expands as
cell migration and stem cell production con...
Malformations of cortical
development
ranging from defective gyral
formation to focal cortical dysplasia
CNS Malformations
• Congenital deviations in form and structure.
– Primary malformations due to genetic or
chromosomal ano...
CNS Malformations often manifest clinically as
neurodevelopmental disorders
• The cerebral cortex plays key role in memory...
Specific malformations of cortical
development
• Abnormal proliferation or apoptosis of glial
and neuronal cells (may be l...
Specific malformations of cortical
development
• Abnormal late neuroblast migration and
cortical organization
– Polymicrog...
Malformations of cortical development:
Extent of involvement
• Diffuse
• Focal
• Gross
• Microscopic
Gross cortical dysplasia
• Agyria/lissencephaly: ‘smooth brain’ or total
absence of convolutions
• Pachygyria: intermediat...
Pachygyria
Agyria or
lissencephaly
Miller-Dieker syndrome
- Rare, 1 per 100,000 live births.
- Microdeletion 17p13.3
Craniofascial abnormalities: microcephal...
Miller-Dieker syndrome
Lateral view
Superior view
Miller-Dieker syndrome
Reversal of the gray-white matter ratio
Large ventricles
Subependymal heterotopic nodules
Normal
Miller-Dieker Syndrome:
abnormal neuroblast migration
inner
outer
Jeffrey A. Golden & Brian N. Harding. (2004). Developmen...
Case study
• 8-year-old female with a history of intractable
epilepsy, normal gross brain development
• She initially pres...
Case study: Focal cortical dysplasia with
dysmorphic cells and balloon cells
• Patient did well, but several weeks later, ...
Kabat J and Krol P. Focal cortical dysplasia – review. Pol J Radio, 2012;77(2):35-43.
Histopathology of FCD type 1a
Abnormal radial lamination and abundant microcolumns
Blumcke et al. The clinico-pathological...
Histopathology of FCD type 1b
Abnormal tangential layer composition
Blumcke et al. The clinico-pathological spectrum of fo...
Histopathology of FCD type 2a
Disorganized cortical layers and dysmorphic neurons
Neu N Abnormal NF
Prominent Nissl bodies...
Histopathology of FCD type 2b
Disorganized cortical layers, dysmorphic neurons and balloon cells
GFAP synaptophysin
•Blumc...
Why do cortical dysplasias cause
epilepsy?
• Abnormal neurons, eg. Balloon cells
– Generate bursting behavior or intrinsic...
Treatment for epilepsies due to malformations
of cortical development
• Medical
– High rate of medical intractability, sup...
Is cortical dysplasia a cause for autism?
• Recent research published in the New England Journal of Medicine
supports this...
References
• Blumcke et al. The clinico-pathological spectrum of focal cortical dysplasias: a
consensus classification pro...
Cortical dysplasia
Cortical dysplasia
Cortical dysplasia
Cortical dysplasia
Cortical dysplasia
Upcoming SlideShare
Loading in …5
×

of

Cortical dysplasia Slide 1 Cortical dysplasia Slide 2 Cortical dysplasia Slide 3 Cortical dysplasia Slide 4 Cortical dysplasia Slide 5 Cortical dysplasia Slide 6 Cortical dysplasia Slide 7 Cortical dysplasia Slide 8 Cortical dysplasia Slide 9 Cortical dysplasia Slide 10 Cortical dysplasia Slide 11 Cortical dysplasia Slide 12 Cortical dysplasia Slide 13 Cortical dysplasia Slide 14 Cortical dysplasia Slide 15 Cortical dysplasia Slide 16 Cortical dysplasia Slide 17 Cortical dysplasia Slide 18 Cortical dysplasia Slide 19 Cortical dysplasia Slide 20 Cortical dysplasia Slide 21 Cortical dysplasia Slide 22 Cortical dysplasia Slide 23 Cortical dysplasia Slide 24 Cortical dysplasia Slide 25 Cortical dysplasia Slide 26 Cortical dysplasia Slide 27 Cortical dysplasia Slide 28 Cortical dysplasia Slide 29 Cortical dysplasia Slide 30 Cortical dysplasia Slide 31 Cortical dysplasia Slide 32 Cortical dysplasia Slide 33 Cortical dysplasia Slide 34 Cortical dysplasia Slide 35 Cortical dysplasia Slide 36 Cortical dysplasia Slide 37 Cortical dysplasia Slide 38 Cortical dysplasia Slide 39
Upcoming SlideShare
Cortical dysplasia and epilepsy
Next
Download to read offline and view in fullscreen.

12 Likes

Share

Download to read offline

Cortical dysplasia

Download to read offline

developmental neuropathology of cortical dysplasia

Related Books

Free with a 30 day trial from Scribd

See all

Related Audiobooks

Free with a 30 day trial from Scribd

See all

Cortical dysplasia

  1. 1. DEVELOPMENTAL NEUROPATHOLOGY OF CORTICAL DYSPLASIA Amanda Rivera-Begeman D.O. Perinatal and Pediatric Pathologist Dell Children’s Medical Center Department of Pathology Austin, TX
  2. 2. Goals of this lecture •Brain development •Neuronal migration, cortical development •Cortical dysplasia and clinical correlates
  3. 3. Brain development - Overview Neurulation (3-4 weeks) Cerebral vesicle formation (4-7 weeks) Corticogenesis (8-16 weeks) Maturation (16 weeks on) Illustration by Lydia V. Kibiuk, Baltimore, MD
  4. 4. Neurulation: weeks 3-4 of embryonic development
  5. 5. Cerebral vesicle formation, AKA ‘regionalization’ (4-7 weeks) gestation Unknown author of diagram, retrieved from internet
  6. 6. Corticogenesis: neural cell migration leads to Cortical plate formation (8-16 wks) Telencephalic wall Illustration by Lydia V. Kibiuk, Baltimore, MD
  7. 7. Neural development Induced by exogenous cues from the microenvironment * Unknown author of diagram, retrieved from internet
  8. 8. Neuronal migration Inner surface Outer surface Telencephalic wall Bear, M., Connors, B., & Paradiso, M. (2007). Neuroscience: Exploring the Brain (Third Edition). Baltimore: Lippincott Williams & Wilkins. Purves, D., Augustine, G., & Fitzpatrick, D. (2004). Neuroscience (Third Edition). Sunderland, MA: Sinauer Associates.
  9. 9. External layer/marginal zone Cortical plate Subcortical plate/external Intermediate zone Intermediate zone/subventricular layer Ventricular layer/germinal matrix Cortical Plate Formation (from 7-16 weeks)
  10. 10. neocortex Molecular layer External granular layer External pyramidal layer Internal granular layer Internal pyramidal layer Multiform layer
  11. 11. Gyral development • Convolutions occur because the cortical surface expands as cell migration and stem cell production continue but proliferation rate of VZ cells decrease. • However, the convolutions (gyri) are not randomly created. • The intermediate zone (subcortical white matter) becomes crisscrossed by a large number of axonal fascicles forming connections that contribute to the shape of the convolution. • It has been hypothesized that the tension created by these fascicles is responsible for the stereotyped shape and orientation of the gyri Toro, R., and Burnod, Y. (2005). A morphogenetic model for the development of cortical convolutions. Cereb. Cortex 15, 1900–1913. Poduri A et. Al. somatic mutation, genomic variation, and Neurological disease. Science 5 July 2013: Vol 341 no. 6141
  12. 12. Malformations of cortical development ranging from defective gyral formation to focal cortical dysplasia
  13. 13. CNS Malformations • Congenital deviations in form and structure. – Primary malformations due to genetic or chromosomal anomalies – Secondary malformations depend on exogenous causes • Developing nervous system is subjected to damage during the whole gestation and early postnatal life. – Hypoxia, trauma, toxins and infectious agents • The earlier the insult in brain development, the more severe the brain malformation
  14. 14. CNS Malformations often manifest clinically as neurodevelopmental disorders • The cerebral cortex plays key role in memory, attention, perceptual awareness, thought, language, and consciousness. • Some common disorders that are neurodevelopmental in origin or have neurodevelopmental consequences when they occur in infancy and childhood: – Autism and autism spectrum disorders – Fetal alcohol spectrum disorder – Motor disorders – Traumatic brain injury (including congenital injuries that cause cerebral palsy) – Communication, speech and language disorders – Genetic disorders, such as fragile-X syndrome – Down syndrome – Attention deficit hyperactivity disorder
  15. 15. Specific malformations of cortical development • Abnormal proliferation or apoptosis of glial and neuronal cells (may be localized or diffuse) – Decreased neuronal number, eg. microencephaly – Increased proliferation, eg. megencephaly – Abnormal proliferation, eg. Tuberous sclerosis/ cortical tubers, neoplastic • Abnormal neuroblast migration – Lissencephaly – Heterotopia
  16. 16. Specific malformations of cortical development • Abnormal late neuroblast migration and cortical organization – Polymicrogyria and schizencephaly – Cortical dysplasia with balloon cells – Microdysgenesis • Other malformations with frequently associated cortical maldevelopment – Holoprosencephaly – failure of differentiation of the prosencephalon
  17. 17. Malformations of cortical development: Extent of involvement • Diffuse • Focal • Gross • Microscopic
  18. 18. Gross cortical dysplasia • Agyria/lissencephaly: ‘smooth brain’ or total absence of convolutions • Pachygyria: intermediate form with rare and broad gyri • Both may coexist in the same brain and may overlie an abnormal cortical plate
  19. 19. Pachygyria Agyria or lissencephaly
  20. 20. Miller-Dieker syndrome - Rare, 1 per 100,000 live births. - Microdeletion 17p13.3 Craniofascial abnormalities: microcephaly with high narrow forehead, low-set ears and small mandible. Neurologic impairment: decreased activity, abnormal tone, profound mental retardation, seizures
  21. 21. Miller-Dieker syndrome Lateral view Superior view
  22. 22. Miller-Dieker syndrome Reversal of the gray-white matter ratio Large ventricles Subependymal heterotopic nodules Normal
  23. 23. Miller-Dieker Syndrome: abnormal neuroblast migration inner outer Jeffrey A. Golden & Brian N. Harding. (2004). Developmental Neuropathology. The International Society of Neuropathology
  24. 24. Case study • 8-year-old female with a history of intractable epilepsy, normal gross brain development • She initially presented in status epilepticus at an outside institution, requiring several weeks of intubation in the ICU. • MRI: abnormal thickening and blurring of the gray- white junction in the inferior posterior frontal lobe and anterior mesial frontal lobe, concerning for focal cortical dysplasias. • Transferred to DCMC, had grid electrodes placed, and eventually had surgery for resection of these areas.
  25. 25. Case study: Focal cortical dysplasia with dysmorphic cells and balloon cells • Patient did well, but several weeks later, her seizures returned and were similar as before. • Imaging revealed residual cortical dysplasia between the two resected foci. • Therefore, the patient was brought back to surgery for a second resection. • Histopathologic examination confirmed residual cortical dysplasia
  26. 26. Kabat J and Krol P. Focal cortical dysplasia – review. Pol J Radio, 2012;77(2):35-43.
  27. 27. Histopathology of FCD type 1a Abnormal radial lamination and abundant microcolumns Blumcke et al. The clinico-pathological spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc task force of ILAE Diagnostic methods commission. Epilepsia. 2011 January; 52(1):158-174.
  28. 28. Histopathology of FCD type 1b Abnormal tangential layer composition Blumcke et al. The clinico-pathological spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc task force of ILAE Diagnostic methods commission. Epilepsia. 2011 January; 52(1):158-174.
  29. 29. Histopathology of FCD type 2a Disorganized cortical layers and dysmorphic neurons Neu N Abnormal NF Prominent Nissl bodies Blumcke et al. The clinico-pathological spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc task force of ILAE Diagnostic methods commission. Epilepsia. 2011 January; 52(1):158-174.
  30. 30. Histopathology of FCD type 2b Disorganized cortical layers, dysmorphic neurons and balloon cells GFAP synaptophysin •Blumcke et al. The clinico-pathological spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc task force of ILAE Diagnostic methods commission. •Epilepsia. 2011 January; 52(1):158-174.
  31. 31. Why do cortical dysplasias cause epilepsy? • Abnormal neurons, eg. Balloon cells – Generate bursting behavior or intrinsic hyperexcitability • Altered synaptic connectivity – More excitatory cortical afferents – Decreased numbers of inhibitory neurons
  32. 32. Treatment for epilepsies due to malformations of cortical development • Medical – High rate of medical intractability, supported by high rates of dysplasia found in epilepsy surgery specimens. – Hospital based study on 2200 adult outpatients with epilepsy found that only 24% of those with cerebral dysgenesis attained seizure freedom (Semah et al., 1998). – Treatment is best guided by choosing appropriate medication for seizure type and epilepsy syndrome • Surgical – best results with Taylor type focal cortical dysplasia • Ketogenic diet – high fat, low carbohydrates has documented efficacy in intractable childhood epilepsy
  33. 33. Is cortical dysplasia a cause for autism? • Recent research published in the New England Journal of Medicine supports this idea – ‘Patches of Disorganization in the Neocortex of Children with Autism’ N Engl J Med 370;13. March 27, 2014 issue, pgs 1209-1219. • Researchers found focal disruption of cortical laminar architecture in the cortexes of a majority of young children with autism. • Their data support a probable dysregulation of layer formation and layer- specific neuronal differentiation at prenatal develomental stages. • Questions that arise: – Are these maldeveloped brains the cause for autism or the first “hit” in putting the brain at a higher risk to further damage from secondary causes (eg. Hypoxia, trauma, toxins, infectious agents) that can occur any time during pre and post natal brain maturation? – Can similar types of epilepsy treatment (medical, surgical, dietary) be done for focal cortical dysplasia and it’s complications in autism?
  34. 34. References • Blumcke et al. The clinico-pathological spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc task force of ILAE Diagnostic methods commission. Epilepsia. 2011 January; 52(1):158-174. • Ellison & Love: Neuropathology: A reference text of CNS pathology. 2004. • Kabat, J and Krol, P. Focal cortical dysplasia – review. Pol J Radiol. 2012;77(2):35-43. • Hamiwka, L and Wirrel, E. Epilepsy in patients with cerebral malformations. Handbook of Clinical Neurology, Vol. 87 (3rd series). Malformations of the Nervous System. Editors: Sarnat, H.B. and Curatolo, p. 2008. Chapter 21. Pages 390-407. • Sadler, T.W. Langman’s Essential Medical Embryology. Lippincott Williams & Wilkins. 2005. Neurulation and establishment of body form (chapter 3, pgs 15-19). Central Nervous System (chapter 9, pgs 103-116). • Gilbert-Barness, Kapur, Oligny & Siebert. Potter’s Pathology of the Fetus, Infant, and Child. Elsvier. 2007. Chapter on Central Nervous System neuropathology. • Stoner R et al. Patches of Disorganization in the Neocortex of Children with Autism. N Engl J Med 370;13 March 27, 2014, pgs. 1209-1219.
  • MonaGonzalez7

    Dec. 5, 2021
  • sandeepmishra794

    Dec. 1, 2021
  • sumitbansal99

    Oct. 14, 2021
  • MythreyiPrakash

    Feb. 9, 2021
  • sandeshsrd

    Jun. 10, 2020
  • RomilPatel29

    Dec. 22, 2019
  • ainazahrazaiyadi

    Dec. 23, 2018
  • TreeTree6

    May. 18, 2018
  • ayanate1984

    May. 8, 2018
  • CatherineJoe2

    Mar. 10, 2018
  • DebabrataPattanayak1

    May. 8, 2017
  • rahulraj7710

    Aug. 6, 2014

developmental neuropathology of cortical dysplasia

Views

Total views

7,326

On Slideshare

0

From embeds

0

Number of embeds

10

Actions

Downloads

151

Shares

0

Comments

0

Likes

12

×