Pathology CNS2

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Pathology CNS2
2013-09-27 05:18:41

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  1. What is an encephalocele?
    • 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.
    • The protruding part is destroyed because of mechanical disruption and ischemia
  2. What is the mcc of brain anomaly?
  3. What is the difference between disruption and malformation brain anomaly?
    • Developmental malformations result from flawed development of the brain--> imbalances of factors that control gene expression during development or chromosomal abnormality--> symmetric or midline, no gliosis
    • Disruption--> result from destruction of the normally developed (or developing) brain and are caused by environmental or intrinsic factors such as fetal infection, exposure of the fetus to harmful chemicals, radiation, and fetal hypoxia.--> asymmetrical, gliosis
  4. What are the biomarkers for NTD?
    • AFP
    • Ach esterase
  5. What are the complications of meningomyelocele?
    Myelomeningoceles occur most commonly in the lumbosacral region, and affected individuals manifest clinical deficits referable to motor and sensory function in the lower extremities as well as disturbances of bowel and bladder control from both the structural abnormality of the cord itself and superimposed infection that extends from the thin, overlying skin.
  6. Which genetic problem can cause NTD?
    polymorphisms in enzymes of folic acid metabolism MTHFR
  7. What are the features of anencephaly?
    • Anencephaly is a malformation of the anterior end of the neural tube, with absence of the brain and calvarium.
    • Forebrain development is disrupted at approximately 28 days of gestation (if primary day 25?), and all that remains in its place is the area cerebrovasculosa, a flattened remnant of disorganized brain tissue with admixed ependyma, choroid plexus, and meningothelial cells.
    • The posterior fossa structures may be spared and the eye, depending on the extent of the skull deficit; descending tracts associated with disrupted structures are, as expected, absent.
    • Adrenal function is absent due to hypothalamic absence
  8. Anencephaly is a ...............
  9. What is the most severe NTD?
    craniorachischisis, is due to defective closure of the hindbrain-cervical junction
  10. What are the problem in Tethered cord syndrome?
    • The tethered cord syndrome (TCS) is a frequent accompaniment of meningmyelocele and other malformations of the lower spine and spinal cord.
    • In the TCS, the conus medullaris is pulled lower than the L2 vertebra or the L1-L2 disc space.
    • This traction causes low back pain, scoliosis, lower extremity weakness and sensory loss, and bowel and bladder dysfunction.
  11. What are the causes of microencephaly?
    chromosome abnormalities, fetal alcohol syndrome, and human immunodeficiency virus 1 (HIV-1)
  12. What is the underlying anomaly in microencephaly?
    a reduction in the number of neurons that reach the neocortex and this leads to a simplification of the gyral folding
  13. During the brain development how might neurons be over or underproduced?
    • The pool of proliferating precursor cells in the developing brain lies adjacent to the ventricular system. Neuronal number is determined by the fraction of proliferating cells that undergo transition into migrating cells with each cell cycle.
    • Early on, most cell divisions yield two more progenitor cells, while as development progresses there are more asymmetric divisions yielding both a progenitor cell and a cell headed for the developing cortex. If excess cells exit the proliferating pool too early, then the overall generation of neurons is reduced; if too few exit during early rounds of division, then the geometric expansion of the proliferating population results in an eventual overproduction of neurons.
  14. What are the scenarios in neuronal migration anomaly?
    • 1. Neurons do not migrate at all from the ventricles (periventricular heterotopia) or migrate half way (subcortical band heterotopia).
    • 2. Some neurons reach the cortex but large numbers do not. No normal cortical layers are formed (lissencephaly, pachygyria, cobblestone cortex). 
    • 3. Neurons over-shoot the cortex and end up in the subarachnoid space (marginal-leptomeningeal glioneuronal heterotopia, cobblestone cortex).
    • 4. The late stage of migration and cortical organization is disrupted (polymicrogyria).
  15. What are the manifestations and genetic basis of Lissencehaly/
    • Cortical sulci, in lissencephaly, are absent except, usually, for the Sylvian fissure.
    • The cortex is thick and consists of the molecular and three neuronal layers
    • mutations in the gene encoding the microtubule-associated protein LIS-1, which complexes with dynein and affects the function of the centrosome in nuclear movement. Homozygous is fatal.
    • Lissencephaly  can also occur from a series of mutations in the genes encoding enzymes responsible for the glycosylation of α-dystroglycan; when this receptor for extracellular matrix components does not have appropriate post-translational modifications, its stability is diminished
    • Another microtubule-associated protein, doublecortin (DCX), is also encoded by a gene on the X chromosome; mutations in this gene result in lissencephaly in males and in subcortical band heterotopias in females. These heterotopias may consist of discrete nodules of neurons sitting in the subcortical white matter or complete ribbons that parody the overlying cortex
  16. What are the features of pachygyria?
    Pachygyria is a milder variant of lissencephaly, characterized by broad gyri and a thick cortex with an abnormal cytoarchitecture. Pachygyria is seen in metabolic CNS disorders, such as the Zellweger Syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and glutaric aciduria IIA. Two key features of the ZS and NALD, deficiency of plasmalogens and elevated very long chain fatty acids, may cause membrane abnormalities that could impair guidance of migrating neurons
  17. What are the features of polymicrogyria?
    • Polymicrogyria is characterized by small, unusually numerous, and irregularly formed cerebral convolutions. The gray matter is composed of four layers (or fewer), with entrapment of apparent meningeal tissue at points of fusion that would otherwise be the cortical surface.
    • Polymicrogyria can be induced by localized tissue injury toward the end of neuronal migration particularly CMV and hypoxic ischemic injury
  18. What are the features of neuronal heterotopia?
    • Migrational disorders that are commonly associated with epilepsy
    • Collections of neurons in inappropriate locations along the migrational pathways
    • If cells never managed to leave their place of birth-->Periventricular heterotopias mutation in filamin A, an actin-binding protein responsible for assembly of complex meshworks of filaments. XL--> male lethality; in females the process of X inactivation separates neurons into those with a normal allele (in the correct location) and those with the mutant allele (in the heterotopia)
    • Another microtubule-associated protein, doublecortin (DCX) --> also XL; mutations in this gene result in lissencephaly in males and in subcortical band heterotopias in females. These heterotopias may consist of discrete nodules of neurons sitting in the subcortical white matter or complete ribbons that parody the overlying cortex
  19. What are the abnormalities in cortex that are caused by ABNORMAL NEURONAL-GLIAL PROLIFERATION OR APOPTOSIS?
    Megalencephaly, microcephaly
  20. Prototype of ABNORMAL CORTICAL ORGANIZATION is............
  21. a spectrum of malformations characterized by incomplete separation of the cerebral hemispheres across the midline.
  22. What are the features of holoprosencephaly?
    • Severe forms manifest midline facial abnormalities, including cyclopia; less severe variants (arrhinencephaly) show absence of the olfactory cranial nerves and related structures.
  23. What is the genetic basis for holoprosencephaly?
    • Sonic Hedgehog (SHH) gene on 7q36 which is important for ventral patterning of the forebrain. SHH a family of secreted proteins synthesized by the notochord and neural plate during neural development.
    • Trisomy 13
  24. What are the features of agenesis of CC?
    • In agenesis of the corpus callosum, a relatively common malformation, there is an absence of the white matter bundles that carry cortical projections from one hemisphere to the other
    • May be normal or associated with MR
  25. What are the characteristic features of Dandy Walker malformation?
    • 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. This cyst represents the expanded, roofless fourth ventricle in the absence of a normally formed vermis.
    • Dysplasias of brainstem nuclei are commonly found in association with Dandy-Walker malformation.
    • This cystpushes the tentorium upwards. Obstruction of CSF flow causes hydrocephalus.
  26. What are the features of Arnold Chiari II malformation?
    • The Chiari type II malformation is a syndrome or association of anomalies characterized by
    • a) a neural tube defect, usually a lumbosacral meningomyelocele 
    • b) abnormalities of the posterior fossa and craniocervical junction and
    • c) hydrocephalus.
    • The abnormality of the posterior fossa and its contents consists of a large foramen magnum, misshapen midline  cerebellum, low insertion of the tentorium and a shallow posterior fossa. As a result of these deformities, the cerebellum and brainstem are crowded and displaced into the cervical canal.
  27. What are the associated features of Chiari II malformation?
    caudal displacement of the medulla, malformation of the tectum, aqueductal stenosis, cerebral heterotopias
  28. What are the features of Chiari type I?
    • In the Chiari I malformation, low-lying cerebellar tonsils extend down into the vertebral canal
    • Often silent
    • Many patients have syringomyelia and some have hydrocephalus.
    • NO NTD
  29. Cystic dilatation of the central canal (hydromyelia) is a feature of the........ while syrengomyelia is a feature  of ..................
  30. What is hydromyelia?
    discontinuous multisegmental or confluent expansion of the ependyma-lined central canal of the cord (CMII)
  31. What is syrengomyelia?
    formation of a fluid-filled cleftlike cavity in the inner portion of the cord (syringomyelia, syrinx) that may extend into the brainstem
  32. What are the symptoms of syringomyelia?
    • Dissociated anesthesia (segmental loss of pain and temperature sensation corresponding to the distribution of the syrinx with preservation of vibration and position sense), denervation atrophy of muscle, and kyphoscoliosis.
    • Dissociated anesthesia is due to damage of the spinothalamic axons which cross anterior to the syrinx. 
    • 2nd and 3rd decade
  33. What is the cause of pain and temperature loss early in syringomyelia?
    early involvement of the crossing anterior spinal commissural fibers