NEUROPATHOLOGY- CONGENITAL ABNORMALITIES

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I. GENERAL POINTS
II. ETIOLOGY OF CONGENITAL ABNORMALITIES
III. NEURAL TUBE DEFECTS (DYSRAPHIC DISORDERS)
IV. ARNOLD CHIARI MALFORMATION (ACM)
V. ANOMALIES OF THE SPINAL CORD
VI. MALFORMATIONS OF THE CEREBELLUM
VII. HOLOPROSENCEPHALY (ARHINENCEPHALY)
VIII. ANOMALIES OF CELL MIGRATION
IX. ABNORMAL SURFACE CONFIGURATIONS OF THE BRAIN
X. MICROCEPHALY
XI. MEGALENCEPHALY
XII. AGENESIS OF THE CORPUS CALLOSUM
XIII. NEUROCUTANEOUS SYNDROMES

VOCABULARY:
Terms you should be familiar with:

Teratogenesis
Trisomy
Neural tube defect
Anencephaly
Cranial meningocele
Spinal meningocele
Myelomeningocele
Myelocele
Arnold Chiari Malformation
Heterotopia
Hydromyelia
Diastematomyelia
Diplomyelia
Dandy Walker malformation
Holoprosencephaly
Cyclopia
Agnathia
Agyria
Pachygyria
Polymicrogyria
Microcephaly
Megalencephaly
Tuberous sclerosis
von Hippel Lindau
Sturge Weber Syndrome
von Recklinghausen

OBJECTIVES: The objectives of this hour are to understand some of the factors that relate to the incidence of congenital anomalies of the CNS, to recognize that the occurrence of most congenital anomalies relates to events that occur very early in gestation, to gain a vocabulary related to these conditions, and to survey briefly some of their features.

I. GENERAL POINTS

• The incidence of malformations is higher in children with intrauterine growth retardation and in multiple pregnancies.
  
  
• Race and geographic factors may be of importance.
  
  
• The development of the brain continues for years after birth and thus the term congenital anomaly applies to some brain conditions that develop postnatally.
  
  
• Inflammatory responses do not occur before the sixth fetal month and parts may be absorbed without trace of neuroglial or connective tissue repair.
  
  
• The same anomaly may occur as a result of genetic or environmental causes.
  
  
• Probably the most important factor in teratogenesis is the timing of the insult, followed by the specific nature of the agent and genetic factors.

II. ETIOLOGY OF CONGENITAL ABNORMALITIES

• Genetic Factors: very few cerebral anomalies are caused by simple Mendelian inheritance, but some examples include:
  
  
  • Forms of microcephaly inherited as autosomal recessive
  • Sex-linked variety of hydrocephalus
  • Hereditary congenital facial paralysis- autosomal dominant
  • Some anomalies have a high risk of recurrence within families
  • Some anomalies are associated with inborn errors of metabolism
    
    
• Cytogenetic Abnormalities
  
  
  • Most important group are the trisomies, e.g., Down's
  • Others include translocations, deletions (e.g., cri du chat), and sex chromosomes (e.g., Turner's, Klinefelter's)
    
    
• Maternal Age
  
  
• Maternal Infections (rubella, cytomegalovirus)

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III. NEURAL TUBE DEFECTS (DYSRAPHIC DISORDERS)

• Anencephaly- Basically a complete absence of the cerebral hemispheres. The calvarium is hypoplastic or absent. If the occipital bones are formed, rudimentary brain stem and cerebellum may be found. 0.5-2 per 1000 live births in US. Females > males. Most common anomaly in humans.
  
  
• Encephalocele and Cranial Meningocele- Consists of a protrusion of brain or meninges through a cranial defect. Most frequent in the occipital region, i.e., 75-80% of cases. The mass of tissue is often voluminous and is usually attached to one of the cerebral hemispheres by a narrow pedicle. Genetic and environmental factors may be of etiologic importance.
  
  
• Spinal Meningocele, Myelomeningocele, and Myelocele- All are usually associated with spina bifida. Meningocele consists of herniation of both dura and arachnoid through a vertebral defect, the spinal cord remaining in its normal position. Meningomyelocele consists of the above in addition to the spinal cord (closed) being herniated as well. Myelocele consists of all the above, but the spinal cord is open and flat with CSF leaking onto the exposed surface. Hydrocephalus commonly occurs in association with all of the above.

IV. ARNOLD CHIARI MALFORMATION (ACM)

• Complex Deformity of the Brain and Cerebellum (Four types)
  
  
  • Type I: Ectopia of the cerebellar tonsils. May be a cause of late onset hydrocephalus, and may be associated with a minor deformity of the medulla.
  • Type II: By far the most common type seen in neonates and usually associated with a lumbar myelomeningocele. Consists of lengthening of the vermis and tonsils of the cerebellum and their downward displacement through the foramen magnum into the spinal canal. Characteristic Z shaped kink at the junction of the medulla and cord. Associated anomalies of the cranial vault are common.
  • Type III: Consists of a cervical spinal bifida, the entire cerebellum being herniated through the foramen magnum.
  • Type IV: Cerebellar hypoplasia.
    
    
• ACM (in practice this refers to type II) usually associated with communicating hydrocephalus. Cerebellar heterotopias are common.
  
  
• Theories of Cause
  
  
  • The spinal cord is tethered or stuck down at its lumbar myelomeningocele, thus not allowing for its normal ascent during development. This leads to downward displacement of the brain stem and cerebellum.
  • Hydrocephalus is the initial event.
  • The pontine flexure fails to form.
  • There are arguments against all of these theories.
    
    
• The malformation develops early in gestation at the age of 10 weeks.

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V. ANOMALIES OF THE SPINAL CORD

• Usually these are described in the adult, so they could represent acquired lesions.
  
  
• Hydromyelia: is an over distension of the central canal. Often more pronounced in the lumbar region. May be asymptomatic and only an incidental finding at autopsy. May be associated with ACM in 40% of cases of the latter.
  
  
• Diastematomyelia and diplomyelia: the former consists of two hemicords that may be in the same or two different dural sacs. May be asymptomatic and is often associated with spina bifida. The latter consists of a duplicated spinal cord.
  
  
• Asymmetry or absence of the ventral pyramidal tracts.

VI. MALFORMATIONS OF THE CEREBELLUM

• Agenesis of the Cerebellum: very uncommon
• Hypoplasia
• Dandy Walker Malformation
• L'hermitte Duclos Disease

VII. HOLOPROSENCEPHALY (ARHINENCEPHALY)

Covers a large spectrum of anomalies from cyclopia to agenesis of one olfactory bulb. The term emphasizes the failure of cleavage of the prosencephalon. In the most severe form, there is an anterior holosphere with no interhemispheric fissure and a single ventricle. The brain is often smaller than normal and the olfactory bulbs and tracts are absent. Optic nerves are absent and gyri are broad and have an abnormal pattern. Brain stem and cranial nerve structures may be normal. Cyclopia and agnathia are the major facial associations.

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VIII. ANOMALIES OF CELL MIGRATION

• Ectopias and Heterotopias: These terms refer to misplaced groups of neurons, such as an island of gray matter in the subcortex. More common in the cerebellum than the cerebrum.
  
  
• Cerebellar Cortical Dysplasia.

IX. ABNORMAL SURFACE CONFIGURATIONS OF THE BRAIN

• Agyria (lissencephaly): Total absence of gyri
  
  
• Pachygyria: A few broad malformed gyri varying in size and number
  
  
• Polymicrogyria: An increased number of gyri some of which may be abnormally small

X. MICROCEPHALY

Small brain usually associated with a small head.

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XI. MEGALENCEPHALY

Proportionate enlargement of the whole brain, usually associated with the presence of a variable mental aberration. Accepted definition is a brain weight 2.5 standard deviations above the mean for age and sex.

• Primary
  
  
• Secondary

XII. AGENESIS OF THE CORPUS CALLOSUM

May be part of a complex malformation or be totally or partially absent in an otherwise normal brain.

XIII. NEUROCUTANEOUS SYNDROMES

• Tuberous Sclerosis
  
  
• von Hippel Lindau's Angiomatosis
  
  
• Sturge Weber Syndrome
  
  
• von Recklinghausen's Disease

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