NEUROPATHOLOGY II

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NEUROPATHOLOGY II

• MALFORMATIONS OF THE CNS.
  DEFINITIONS.
  Malformations
  
  -primary disturbance of embryonic
  or fetal development
  Field defect
  
  Disruption
  
  -secondary compromise of development due to
  vascular events, infections, etc.

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NEUROPATHOLOGY II

• DEFINITIONS....
  Deformation
  
  -external mechanical influences affect
  ing development
  
  Dysplasia
  -abnormal neuronal
  clustering/localiza
  tion secondary to neuronal migrational
  defects

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NEUROPATHOLOGY

• Gestation Embryogenesis Effects
  1st/2nd wk
  zygote?3germ lay. Death
  
  Cranioschisis
  3rd-4th wk neural tube form. Anencephaly
  
  Anterior pore clos. Rachischisis
  Posterior
  pore clos. Encephalocele
  Meningomyel.
  Spina
  bifida
  Arnold-Chiari
  Dandy-Walker
  
  

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NEUROPATHOLOGY II

• Gestation Embryogenesis Effect
  5th-6th
  wk -develop.face/forebr.
• -differentiat.prosence
  Faciotelence-
  phaly?olfact.tract, phalic
  malfor
  optic vesicles,telence
  mation
  phalon/diencephalon
  -cleavage of
  telencep. Holoprosen-
  
  into cerebral hemisp. cephaly
  

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NEUROPATHOLOGY II

• Gestation Embryogenesis Effects
  6th wk-4th
  -neuronal/glial Microceph
  mo.
  prolif./migration Megalenc.
  (develop of brain
  Lissencep.
  cortex,meninges, Pachygyria
  ventricles,foram.,
  Polymicro-
  circul. of CSF) gyria
  
  Heterotop.

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NEUROPATHOLOGY II

• Gestation Embryogenesis Effects
  5th month -glial different.
  Porenceph.
  (astrocytes?nu- Hydranen-
  
  trition,oligodend. cephaly
  
  ?myelination)
  -primary sulci appear
  

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NEUROPATHOLOGY II

• Gestation Embryogenesis Effects
  6th month -neuronal
  organiz. Downs
  and architectonic syndrome
  (dendritic/axonal
  Hypothyr.
  connections,syna Phenilket.
  psis formation,apo-
  
  ptosis, myelination)
  7h-9th mos. -second.sulci appear
  

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NEUROPATHOLOGY II

• CAUSES OF MALFORMATIONS.
  Chromosomal abnormalities
  -Trisomy 9, 13, 18, 21
  - Deletions
  4p, 17p
  -Gene mutations
  
  Radiation
  Viral infections
  
  -Herpes simplex/Varicella zoster
  -Cytomegalovirus
  
  -Rubella
  
  Toxoplasmosis

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NEUROPATHOLOGY II

• CAUSES OF MALFORMATIONS...
  Metabolic
  -Maternal
  Diabetes mellitus
  Holoprosencephaly
  Sacral agenesis
  
  -Maternal phenylketonuria
  Microcephaly
  
  -Anticonvulsivants(phenytoin)
  Microcephaly
  2x
  risk of mental retardation
  1-2 risk of spina
  bifida(valproic acid)
  -Dietary deficiency(folic acid?neural
  tube defects)

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NEUROPATHOLOGY II

• CAUSES OF MALFORMATIONS...
  -Retinoic acid/Isotretinoin(retinoid)?
  Hydrocephalus,
  holoprosencephaly,
  microcephaly,abnormal cerebral/cere
  bellar
  cortical migration, cerebellar
  hypoplasia, agenesis of vermis,cerebellar
  microgenesis,heterotopia, focal
  agyria,
  calcification
  -Warfarin?microcephaly, meningocele,
  Dandy-Walker
  malf.,agenesis of corpus callosum and
  diffuse cerebral atrophy

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NEUROPATHOLOGY II

• CAUSES OF MALFORMATIONS...
  Alcohol
  
  -Fetal-alcohol syndrome
  0.4-3.5/live births
  
  190/1000 in some North American
  Indian pop.(genetic? poverty?)
  Neonatal mortality-5.8-17
  Microcephaly,microphta
  lmia,mental re
  tardation,hyperactivity,motor problems
  Growth
  deficiency(often below 10th percentile)

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NEUROPATHOLOGY II

• CAUSES OF MALFORMATIONS...
  
• Cocaine
  
  -Myelomeningocele, encephalocele, agenesis
  of corpus callosum,hetero
  topias, schizencephaly, etc.

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NEUROPATHOLOGY II

• MAJOR GROUPS OF MALFORM....
• Neural tube closure defects
• Disorders of forebrain induction
• Neuronal migration defects
• Encephaloclastic defects

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NEUROPATHOLOGY II

• NEURAL TUBE DEFECTS(Dysraphic disorders)
  
  Primary defects in closure of
  neuropore
  -Anencephaly
  -Craniorachischisis
  
  -Myelomeningocele
  Primary bone
  defects(abnormality in axial mesoderm
  development)
  -Spina bifida occulta
  -Encephalocele
  
  -Meningocele

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NEUROPATHOLOGY II

• ANENCEPHALY
• Is the MOST common congenital malfor
  mation of the brain
• Known as far back as Egyptian antiquity
• Compared to the toad(Morgagni,1761)
• Geographic variation in incidence
  -1-6 / 1000 in
  Ireland and Wales
  -0.5-2 / 1000 in US

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ANENCEPHALY
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ANENCEPHALY
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NEUROPATHOLOGY II

• ANENCEPHALY...
  Etiology unknown
  
  Possible risk factors
  -Geographic
  location
  -Socioeconomic factors
  -Diet
  ? folic acid deficiency
  -Genetic? few familial cases observed
  More common in females

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NEUROPATHOLOGY II

• ANENCEPHALY....
  -Hypoplasia or absence of cranium
  -Shallow
  orbits with protrusion of eyes
  -Hypoplastic lungs
  -Large
  thymus
  -Abnormal pituitary(lack of
  hypothalamus/
  neurohypophysis)
  -Other abnormalities
  adrenal hypoplasia

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NEUROPATHOLOGY II

• ANENCEPHALY....
  -Associated
  craniorachischisis
  -Area cerebrovasculosa
  
  -Prenatal Dx increased maternal serum/am
  niotic
  A-fetoprotein
  -Recurrence risk of 3-5

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NEUROPATHOLOGY II

• MYELOMENINGOCELE.
  Herniation of both meninges/spinal cord through
  a large vertebral defect
  Most often lumbosacral
  Frequent
  association w/hydrocephalus
  -Arnold-Chiari malformation type II
  Area
  medullovasculosa
  Meningocele herniation of
  meninges only
  Occult spina bifidamildest form of neural
  tube defect

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EXENCEPHALY
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NEUROPATHOLOGY II

• SPINAL DYSRAPHISM(spina bifida).
  It may be an asymptomatic bone defect
  (spina bifida
  occulta)
  Also, it can be a severe malformation
  w/ flattened
  and disorganized segment of spinal cord
  associated to an outpouching of meninges

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SPINA BIFIDA
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NEUROPATHOLOGY II

• ARNOLD-CHIARI MALFORMATION.
  There are 4 types
  
  Type I cerebellar tonsillar herniation
  Type II- malformation of
  craniobasal bone,
  shallow posterior fossa
  Type
  III-occipito-cervical bony defect
  -occipital encephalocele
  -herniation of
  cerebellum into en
  cephalocele
  Type IV-cerebellar
  hypoplasia

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NEUROPATHOLOGY II

• ARNOLD-CHIARI MALFORMATION...
  TYPE II
  -Herniation of
  inferior cerebellar vermis
  -Elongation and downward
  displacement of
  medulla and cervical cord
  -Malformation of
  craniobasal bone, shallow
  posterior fossa

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NEUROPATHOLOGY II

• ARNOLD-CHIARI MALFORMATION...
  Associated hydrocephalus,
  meningomyelo cele,
  aqueductal stenosis or atresia, ventri
  cular neuronal heterotopia,
  microgyria, beaking of
  tectum
  Craniolacunae single or
  multiple translu cent
  thinning of cranium dissapears at age
  of 1-2 yrs.
  

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NEUROPATHOLOGY II

• DANDY-WALKER MALFORMATION.
  Characterized by enlarged posterior
  fossa?cerebellar vermis is absent or rudimentary
  in its anterior portion.
• It is a large midline cyst lined by ependyma
  and is contigous
  w/leptomeninges on its outer surface?cyst that
  represents roofless 4th ventricle in abscence of
  vermis.
• Dysplasias of brain stem commonly found as
  associated malformation

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NEUROPATHOLOGY II

• SYRINGOMYELIA.
  About 90 of cases associated
  w/Arnold- Chiari
  type I malformation(tonsillar herniat.)
  Wasting and weakness of hand
  and fore-
  arm muscles, dissociated anesthesia of upper
  limbs
  Kyphoscoliosis or
  Charcots joints
  Slowly progressive
  Syringobulbia may be present

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NEUROPATHOLOGY II

• SYRINGOMYELIA....
  Characterized by formation of a
  fluid-filled cleft-like cavity in the inner cord
  Lesion
  associated w/destruction of gray and white matter
  in the vacinity, surrounded by a dense reactive
  gliosis
  The formed cavity may be extended from
  the cervical spinal cord upward into the brainstem

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NEUROPATHOLOGY II

• NEURONAL MIGRATION DEFECTS.
• Cerebral cortical dysplasia.
• (A) Status verrucosus
• (B) Four layered cortex
• (C) Irregular cord-like cortical dysplasia

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NEUROPATHOLOGY II

• NEURONAL MIGRATION...
• Cerebral cortical dyplasia...
• -Lissencephaly(agyria)
• -Pachygyria
• smooth brain 4 layered cortex

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Pachygyria
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NEUROPATHOLOGY II

• NEURONAL MIGRATION....
  Cerebral cortical dysplasia...
• -Miller-Dieker syndrome
  Microencephaly
• Seizures
• Mental retardation
• Furrowed forehead
• Neonatal jaundice
• Purpura
• Deletion of L1S1 gene,chromosome
  17p13.3(90 of patients)

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NEUROPATHOLOGY II

• NEURONAL MIGRATION....
• Cerebral cortical dysplasia...
• -Polymicrogyria
• Increased number of gyri
  w/
  abnormal cytoarchitecture
  (4 layers of cortex)

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NEUROPATHOLOGY II

• NEURONAL MIGRATION...
• Cerebral cortical dysplasia...
• -Polymicrogyria...
• Etiology
• Ischemia,infections(CMV,
  toxoplasma,varicella zoster,
• syphilis)
• Familial syndromes
• Metabolic diseases(peroxisomal,
• mitochondria encephalopathy,etc)

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NEUROPATHOLOGY II

• DISORDERS OF FOREBRAIN INDUCT.
  Holoprosencephaly.
• -Anomalies of prosencephalic outgrowth
  and cleavage
• -Types classified by degree of gyral de
  velopment
• Alobar
• Semilobar
• Lobar

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NEUROPATHOLOGY II

• DISORDERS OF FOREBRAIN INDUCT...
  Holoprosencephaly....
• -Varying grades of facial dysmorphirms
  the face predicts the brain
  -Other systemic
  malformations are freq. -Mild
  form of these is known as arrhinen
  cephaly w/lack
  of development of the
  olfactory bulb and tract

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NEUROPATHOLOGY II

• DISORDERS OF FOREBRAIN INDUCT...
  Holoprosencephaly....
• -Incidence 1/16,000-1/31,000
• -MF 13
• -Chromosomal abnormalities
• Trisomy 13(most common), 18, etc
• Familial AR or AD or X-linked R
• Maternal diabetes
• Maternal infectionstoxoplasma,rubella
• Fetal-alcohol syndrome

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NEUROPATHOLOGY II

• ENCEPHALOCLASTIC DEFECTS.
• Porencephaly
• -Defects in the wall of the cerebral he
  misphere with
  communication between
  ventricle and the surface
• -Basket brain(Schizencephaly) w/seve
  re bilateral hemispheric
  porencephalic
• defects?smooth walled and surrounded
  by gyral pattern

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NEUROPATHOLOGY II

• ENCEPHALOCLASTIC DEFECTS.....
• Porencephaly...
• Clinical
• -Spasticity
• -Seizures
• -Severe mental retardation
• -Blindness
• -Survival into adult life in some patients
• Other associated anomalies

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NEUROPATHOLOGY II

• Basket brain(Schizencephaly)
  Etiology unknown
  
  -Presumably destructive events occurring
  early during fetal life
• -Events antedate the acquisition of mature
  astroglial response or
  completion of convo-
  lutional development
• -Vascular insults, infections, trauma, etc.

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NEUROPATHOLOGY II

• ENCEPHALOCLASTIC DEFECTS...
  Hydranencephaly.
  -Etiology
• Vascular events
• Maternal infections-CMV,toxoplasma
  Trauma
• -Clinical feature
• Seizures,spascity,poor psychomotor
  
  development
• Survival is short but can be up to 1 yr or
  
  longer

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NEUROPATHOLOGY II

• ENCEPHALOCLASTIC DEFECTS...
• Agenesis of corpus callosum.
• -Relatively a common malformation(1 in
  19,000 autopsies and 2.3 in chil
  dren w/mental retardation)
• -Defect that can be partial or complete
• -May present seizures, intellectual im-
  pairment, psychosis(due mostly
  to other
• associated anomalies)

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NEUROPATHOLOGY II

• ENCEPHALOCLASTIC DEFECTS....
• Multicystic encephalomalacia.
• Encephloclastic mechanism as in porencephaly
  and hydranencephaly
• -Mainly related to vascular events ocurring in
  the third trimester or perinatal life
• -Severe forms are due to global hemispheric
  necrosis
  
  -May also
  follow viral infections

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NEUROPATHOLOGY II

• ENCEPHALOCLASTIC DEFECTS...
• Multicystic encephalomalacia...
• -Are cavities ragged and irregular without
  cortical malformations
• -Gliosis and lipid laden macrophages are his
  tological
  characteristics
  

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NEUROPATHOLOGY II

• PERINATAL BRAIN INJURY.
• Is a common cause of cerebral palsy,
  affecting 1-2/1000 live births in UK and
  resulting in 1 million of neonatal deaths
  annually.
• Characterized by seizures mental retardation
• Typical white matter injury?periventricular
  leukomalacia(PVL)

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