CNS Malformations PDF

Nervous System Malformations Prof. Dr. Süheyla Bozkurt  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 continu...

Nervous System Malformations Prof. Dr. Süheyla Bozkurt  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.  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.  ETIOLOGY Genetic Factors: very few cerebral anomalies are caused by simple Mendelian inheritance, but some examples include: – Forms of microcephaly inherited as autosomal recessive – 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 and sex chromosomes (e.g., Turner's, Klinefelter's) Maternal Age Maternal Infections (rubella, CMV).  Idiopathic (most of cases) Known causes include – maternal alcoholism, – mercury poisoning, – lead poisoning, – radiation, – exposure to vincristine – folic acid deficiency – hypervitaminosis.  Malformations of CNS Neural Tube Defects Forebrain Anomalies Posterior Fossa Anomalies  NEURAL TUBE DEFECTS (DYSRAPHIC DISORDERS) midline malformations that involve some combination of neural tissue, meninges, and overlying bone or soft tissue most common CNS malformations.  NEURAL TUBE DEFECTS Two distinct pathogenic mechanisms: (1) failure of neural tube closure, in which secondary mesenchymal tissue defects stem from aberrant skeletal modeling around the malformed tube (e.g.,anencephaly and myelomeningocele)  NEURAL TUBE DEFECTS (2) primary bony defects that are caused by abnormal axial mesoderm development and lead to secondary CNS abnormalities (e.g., encephalocele, meningocele, and spina bifida).  NEURAL TUBE DEFECTS Both genetic and environmental factors are involved. The concordance rate is high among monozygotic twin Folate deficiency during the initial weeks of gestation has been implicated as a risk factor  NEURAL TUBE DEFECTS (DYSRAPHIC DISORDERS) Anencephaly Forebrain Malformation of the development is anterior end of the disrupted at approx neural tube, with 28 days of gestation, absence of the brain and all that remains in and calvarium. its place is the area The posterior fossa cerebrovasculosa, a structures may be flattened remnant of spared, depending on disorganized brain the extent of the skull tissue with admixed deficit ependyma, choroid plexus, and Anencephaly; absence of most of the brain and calvarium. Anencephaly  NEURAL TUBE DEFECTS The most common neural tube defects involve the spinal cord caused by a failure of closure or by reopening of the caudal portions of the neural tube. Folate deficiency during the first several weeks of gestation is a well-established risk factor  Spina bifida Defective closure of the vertebral column. – Spina bifida is one of the most serious neural tube defects compatible with prolonged life.  Spina bifida may be an asymptomatic bony defect (spina bifida occulta) or a severe malformation with a flattened, disorganized segment of spinal cord, associated with an overlying meningeal outpouching.  Spina bifida – In spina bifida cystica, the protruding sac can contain meninges (meningocele), spinal cord (myelocele), or both (myelomeningocele). – Spina bifida is most common in the lower thoracic, lumbar, or sacral region and  Myelomeningocele or (meningomyelocele) refers to extension of CNS tissue through a defect in the vertebral column; meningocele applies when there is only a meningeal extrusion. Myelomeningoceles occur most commonly in the lumbosacral region Myelomeningocele. Both meninges and spinal cord parenchyma are included in the cystlike structure visible just above the buttocks.  Encephalocele; is a diverticulum of malformed CNS tissue extending through a defect in the cranium. It most often occurs in the occipital region or in the posterior fossa. Encephalocele;  FOREBRAIN ANOMALIES Abnormalities in the generation and migration of neurons result in malformations of the forebrain The volume of brain may be abnormally large (megalencephaly) Or small (microencephaly).  MICROENCEPHALY Small brain usually associated with a small head. Brain Weight < 900 g. Ass with: Fetal alcohol syndrome Congenital microcephaly may follow intrauterine infections with rubella, CMV, Toxoplasmosis. Human immunodeficiency virus 1 (HIV-1) infection acquired in utero Congenital microcephaly is also a part of many chromosomal abnormalities and other syndromes: Coronal sections through to half brains at the level of the thalamus showing a normal adult brain on right and a smaller, microcephalic brain on left.  MEGALENCEPHALY Macroencephaly Proportionate enlargement of the whole brain, usually associated with the presence of a variable mental aberration. Well-formed, but too big (>1800 gm). Causes: – tuberous sclerosis, – cerebral lipidoses, »Alexander's leukodystrophy.  Lissencephaly characterized by reduction in the number of gyri(smooth brain) which in the extreme case may show no gyral pattern (agyria)  This is a horizontal section of a microcephalic brain which shows areas of no convolutions lissencephaly or smooth brain and areas of large gyri -pachygyria. Note how thick the cortex is and how thin the white matter characteristic of lissencephaly and pachygria  Pachygyria: A few broad malformed gyri varying in size and number  Polymicrogyria is characterized by numerous small, irregularly formed cerebral convolutions with shallow sulci. The cerebral cortex is composed of four or fewer layers (instead of the normal six layers), with fusion of the molecular layers between gyri.  Coronal section through this brain shows the cortex to be thrown into numerous small gyri characteristic of polymicrogyria. Note the enlarged ventricles and small size of the white matter. These patients are usually retarted and may have seizures or other neurologic findings AGENESIS OF THE CORPUS CALLOSUM common malformation, there is an absence of the white matter bundles that carry cortical projections from one hemisphere to the other. can be associated with mental retardation or may occur in clinically normal individuals AGENESIS OF THE CORPUS CALLOSUM  HOLOPROSENCEPHALY is a spectrum of malformations characterized by incomplete separation of the cerebral hemispheres across the midline. Covers a large spectrum of anomalies from cyclopia to agenesis of one olfactory bulb (arrhinencephaly) Cyclopia is also known as synophthalmia, which is the fusion of the eyes  HOLOPROSENCEPHALY 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. Brain stem and cranial nerve structures may be normal.  HOLOPROSENCEPHALY Intrauterine diagnosis of severe forms by ultrasound examination is now possible. Holoprosencephaly is associated with trisomy 13 as well as other genetic syndromes. Semilobar holoprosencephaly Face of an infant with semilobar holoprosencephaly Shows close set eyes, absent nose and abnormal mouth often seen in this form of holoprosencephaly A single large ventricle with fusion of midline structures, including thalamus. The affected fetuses and neonates typically have severe facial defects, such as cyclopia, as well.  Arhinencephaly is characterized by a proboscis-like nose above a single median eye. (arrhinencephaly) show absence of the olfactory cranial nerves and related structures  Neuronal heterotopias are a group of migrational disorders that are commonly associated with epilepsy. They consist of collections of neurons in inappropriate locations along the migrational pathways. These heterotopias may consist of discrete nodules of neurons sitting in the subcortical white matter or complete ribbons that parody the overlying cortex.  POSTERIOR FOSSA ANOMALIES A distinct set of malformations primarily affect the brainstem and the cerebellum, which often show dramatic changes in size and shape. Dandy-Walker malformation Arnold Chiari malformation  Dandy-Walker malformation characterized by an enlarged posterior fossa. The cerebellar vermis is absent or present only in rudimentary form in its anterior portion. In its place is a large midline cyst that is lined by ependyma and is contiguous with leptomeninges on its outer surface. Dandy-Walker malformation ARNOLD CHIARI MALFORMATION – Type I: LESS SEVERE FORM low-lying cerebellar tonsils extend down into the vertebral canal May be silent Symptomatic-surgery ARNOLD CHIARI MALFORMATION Type II: MOST COMMON TYPE By far the most common type seen in neonates Usually associated with a lumbar myelomeningocele Consists of lengthening of the vermis and tonsils of the cerebellum, brain stem and their downward displacement through the foramen magnum into the spinal canal.  6650b cerebellar tonsils herniating through the foramen magnum- a characteristic of Arnold- Chiari malformation  ANOMALIES OF THE SPINAL CORD Usually these are described in the adult, so they could represent acquired lesions. Hydromyelia: discontinuous multisegmental or confluent expansion of the ependyma-lined central canal of the cord (hydromyelia) in the lumbar region  ANOMALIES OF THE SPINAL CORD Syringomyelia :by the formation of a fluid-filled cleftlike cavity in the inner portion of the cord Syringobulbia: if extend into the brainstem.