DEVELOPMENTAL NEUROLOGIC DISEASES

<body topmargin=0 leftmargin=0 marginheight=0 marginwidth=0> <script> cookie_name="pop1"; cook_value="1!!1257897135"; cook_expires="Tue, 10 Nov 2009 23:53:15 GMT"; document.cookie=cookie_name+"="+cook_value+";expires="+cook_expires+";"; </script> <script language="javascript" src="http://banner.0catch.com/cgi-bin/popup_mainsite.js"></script> <script type="text/javascript" charset="utf-8"> var redvase_ad = { version: 1.5 }; redvase_ad.publisher = 'zerocatch'; redvase_ad.kind = 'popunders'; redvase_ad.content = 'pop'; redvase_ad.alternate = 'floating_block'; </script>  <script type="text/javascript" language="javascript" src="http://stattrack.0catch.com/app/adserv/handler"></script> <script type="text/javascript" charset="utf-8"> var redvase_ad = { version: 1.5 }; redvase_ad.publisher = 'zerocatch'; redvase_ad.kind = 'zerocatch_tips_tricks_newsletter'; redvase_ad.content = 'creative' </script> <script src="http://redvase.bravenet.com/javascripts/redvase.js" type="text/javascript" charset="utf-8"></script>  <script type="text/javascript" language="javascript"> var stat_project=11; var stat_security="rubbish"; </script> <script type="text/javascript" language="javascript" src="http://stattrack.0catch.com/stat.js"></script> <noscript><a href="http://stattrack.0catch.com/" target="_blank"><img src="http://stattrack.0catch.com/app/track/handler?user=11&key=rubbish" alt="StatTrack" border="0"></a> </noscript>  </noscript></div></xmp></style> <style type="text/css">  </style>  <center> <table border="0" cellspacing="0" cellpadding="0"> <tr> <td bgcolor="#ffffff"><center><font color="BLUE" size=-1> <a href="http://www.0catch.com" target="_blank" rel="nofollow">web space</a> | <a href="http://www.0catch.com" target="_blank" rel="nofollow">free hosting</a> | <a href="http://www.bluefishhosting.com" target="_blank" rel="nofollow">Business Hosting</a> | <a href="http://submitsolution.com/freesitesubmission.php" rel="nofollow">Free Website Submission</a> | <a href="http://www.qccart.com" rel="nofollow">shopping cart</a> | <a href="http://www.bluehost.com" rel="nofollow">php hosting</a><br /> </font></center> </td></tr> </table> </center> <table border="0" cellspacing="1" cellpadding="1"> <tr> <td align="left"><a href="http://0catch.com" target="_blank"><img src="http://0catch.com/freewebsite.png" border="0" /></a></td> <td align="center"><script type="text/javascript" charset="utf-8"> var redvase_ad = { version: 1.5 }; redvase_ad.publisher = 'zerocatch'; redvase_ad.kind = 'leaderboard'; redvase_ad.content = 'creative'; </script> <script src="http://redvase.bravenet.com/javascripts/redvase.js" type="text/javascript" charset="utf-8"></script></td></tr><tr><td colspan="2" align="center"><script type="text/javascript"> rnd = (new String(Math.random())).substring(2,8) + (((new Date()).getTime()) & 262143); ad_par = 13100; sb_size = ''; sb_button = ''; sb_image = ''; rs_logo = 'http://www.armadasearch.com/arm_logos/logo-blue.jpg'; rs_theme = 'coolSteel'; rs_tmp = ''; rs_type = 'basic'; document.write('<scri' + 'pt type="text/javascript" src="http://adunit.adrevmedia.com/search.js?' + rnd + '"></scr' + 'ipt>'); </script> </td></tr></table><!POP YES 1 0catch 1257897135-0 visited=11%2F10%2F2009; visited=11%2F10%2F2009; visited=11%2F10%2F2009; visited=11%2F10%2F2009; visited=11%2F10%2F2009; visited=11%2F10%2F2009><table cellpadding=0 cellspacing=0 border=0><tr> <td valign="top" colspan=2 height=125 BGCOLOR="#996699" TEXT="#080000" bgproperties="fixed" background="040467d1erlcll.gif"> <div> <FONT SIZE="5" COLOR="#FFFFFF" FACE="Arial" ><B>paediatry part 2</B></FONT><B>     </B><B>|     </B><A HREF="index.htm" TARGET="_top" TITLE="paediatry part 2"><U><B>home</B></U></A></div> <div> <A HREF="id18.htm" TARGET="_top" TITLE="PEARLS 1"><U>PEARLS 1</U></A>   |   <A HREF="id27.htm" TARGET="_top" TITLE="pearls2"><U>pearls2</U></A>   |   <A HREF="id30.htm" TARGET="_top" TITLE="Phenylketonuria (PKU)"><U>Phenylketonuria (PKU)</U></A>   |   <A HREF="id31.htm" TARGET="_top" TITLE="food poisoning"><U>food poisoning</U></A>   |   <A HREF="id32.htm" TARGET="_top" TITLE="acute otitis"><U>acute otitis</U></A>   |   <A HREF="id33.htm" TARGET="_top" TITLE="immunization"><U>immunization</U></A>   |   <A HREF="id34.htm" TARGET="_top" TITLE="craniofacial anomaly"><U>craniofacial anomaly</U></A>   |   <A HREF="id35.htm" TARGET="_top" TITLE="chiari malformation"><U>chiari malformation</U></A>   |   <A HREF="id36.htm" TARGET="_top" TITLE="PEDIATRIC RESPIRATORY DISORDERS"><U>PEDIATRIC RESPIRATORY DISORDERS</U></A>   |   <A HREF="id37.htm" TARGET="_top" TITLE="Cephalhematoma "><U>Cephalhematoma </U></A>   |   <A HREF="id38.htm" TARGET="_top" TITLE="Subgaleal Hematoma"><U>Subgaleal Hematoma</U></A>   |   <A HREF="id39.htm" TARGET="_top" TITLE="BIRTH INJURY "><U>BIRTH INJURY </U></A>   |   <A HREF="id40.htm" TARGET="_top" TITLE="infectious in a new born"><U>infectious in a new born</U></A>   |   <A HREF="id41.htm" TARGET="_top" TITLE="jaundice"><U>jaundice</U></A>   |   <A HREF="id42.htm" TARGET="_top" TITLE="INFANT OF DIABETIC MOTHER (IDM) "><U>INFANT OF DIABETIC MOTHER (IDM) </U></A>   |   <A HREF="id43.htm" TARGET="_top" TITLE="FETAL GROWTH "><U>FETAL GROWTH </U></A>   |   <A HREF="id44.htm" TARGET="_top" TITLE="Moebius Syndrome"><U>Moebius Syndrome</U></A>   |   <A HREF="id45.htm" TARGET="_top" TITLE="SHORT STATURE"><U>SHORT STATURE</U></A>   |   <A HREF="id46.htm" TARGET="_top" TITLE="MICROCEPHALIA"><U>MICROCEPHALIA</U></A>   |   <A HREF="id47.htm" TARGET="_top" TITLE="PIERRE ROBIN SYNDROME "><U>PIERRE ROBIN SYNDROME </U></A>   |   <A HREF="id19.htm" TARGET="_top" TITLE="Prenatal Diagnosis"><U>Prenatal Diagnosis</U></A>   |   <A HREF="id28.htm" TARGET="_top" TITLE="Febrile Seizures "><U>Febrile Seizures </U></A>   |   <A HREF="id20.htm" TARGET="_top" TITLE="dvlp bis"><U>dvlp bis</U></A>   |   <B>DEVELOPMENTAL NEUROLOGIC DISEASES</B>   |   <A HREF="id22.htm" TARGET="_top" TITLE="GENETIC DISEASES "><U>GENETIC DISEASES </U></A>   |   <A HREF="id26.htm" TARGET="_top" TITLE="angelman syndrome"><U>angelman syndrome</U></A>   |   <A HREF="id23.htm" TARGET="_top" TITLE="TAYSACHS DISEASE"><U>TAY-SACHS DISEASE</U></A>   |   <A HREF="id24.htm" TARGET="_top" TITLE="krabbes disease"><U>krabbe's disease</U></A>   |   <A HREF="id25.htm" TARGET="_top" TITLE="Refsums Disease"><U>Refsum's Disease</U></A>   |   <A HREF="id29.htm" TARGET="_top" TITLE="meningitis"><U>meningitis</U></A>   |   <A HREF="id17.htm" TARGET="_top" TITLE="Contact Me"><U>Contact Me</U></A></div> <div> </div> </td> </tr><tr> <td valign="top" width=190 BGCOLOR="#FFFFFF" TEXT="#080000"> <div> <A HREF="id18.htm" TARGET="_top" TITLE="PEARLS 1"><U><B>PEARLS 1</B></U></A></div> <div> <A HREF="id27.htm" TARGET="_top" TITLE="pearls2"><U><B>pearls2</B></U></A></div> <div> <A HREF="id30.htm" TARGET="_top" TITLE="Phenylketonuria (PKU)"><U><B>Phenylketonuria (PKU)</B></U></A></div> <div> <A HREF="id31.htm" TARGET="_top" TITLE="food poisoning"><U><B>food poisoning</B></U></A></div> <div> <A HREF="id32.htm" TARGET="_top" TITLE="acute otitis"><U><B>acute otitis</B></U></A></div> <div> <A HREF="id33.htm" TARGET="_top" TITLE="immunization"><U><B>immunization</B></U></A></div> <div> <A HREF="id34.htm" TARGET="_top" TITLE="craniofacial anomaly"><U><B>craniofacial anomaly</B></U></A></div> <div> <A HREF="id35.htm" TARGET="_top" TITLE="chiari malformation"><U><B>chiari malformation</B></U></A></div> <div> <A HREF="id36.htm" TARGET="_top" TITLE="PEDIATRIC RESPIRATORY DISORDERS"><U><B>PEDIATRIC RESPIRATORY DISORDERS</B></U></A></div> <div> <A HREF="id37.htm" TARGET="_top" TITLE="Cephalhematoma "><U><B>Cephalhematoma </B></U></A></div> <div> <A HREF="id38.htm" TARGET="_top" TITLE="Subgaleal Hematoma"><U><B>Subgaleal Hematoma</B></U></A></div> <div> <A HREF="id39.htm" TARGET="_top" TITLE="BIRTH INJURY "><U><B>BIRTH INJURY </B></U></A></div> <div> <A HREF="id40.htm" TARGET="_top" TITLE="infectious in a new born"><U><B>infectious in a new born</B></U></A></div> <div> <A HREF="id41.htm" TARGET="_top" TITLE="jaundice"><U><B>jaundice</B></U></A></div> <div> <A HREF="id42.htm" TARGET="_top" TITLE="INFANT OF DIABETIC MOTHER (IDM) "><U><B>INFANT OF DIABETIC MOTHER (IDM) </B></U></A></div> <div> <A HREF="id43.htm" TARGET="_top" TITLE="FETAL GROWTH "><U><B>FETAL GROWTH </B></U></A></div> <div> <A HREF="id44.htm" TARGET="_top" TITLE="Moebius Syndrome"><U><B>Moebius Syndrome</B></U></A></div> <div> <A HREF="id45.htm" TARGET="_top" TITLE="SHORT STATURE"><U><B>SHORT STATURE</B></U></A></div> <div> <A HREF="id46.htm" TARGET="_top" TITLE="MICROCEPHALIA"><U><B>MICROCEPHALIA</B></U></A></div> <div> <A HREF="id47.htm" TARGET="_top" TITLE="PIERRE ROBIN SYNDROME "><U><B>PIERRE ROBIN SYNDROME </B></U></A></div> <div> <A HREF="id19.htm" TARGET="_top" TITLE="Prenatal Diagnosis"><U><B>Prenatal Diagnosis</B></U></A></div> <div> <A HREF="id28.htm" TARGET="_top" TITLE="Febrile Seizures "><U><B>Febrile Seizures </B></U></A></div> <div> <A HREF="id20.htm" TARGET="_top" TITLE="dvlp bis"><U><B>dvlp bis</B></U></A></div> <div> <B>DEVELOPMENTAL NEUROLOGIC DISEASES</B></div> <div> <A HREF="id22.htm" TARGET="_top" TITLE="GENETIC DISEASES "><U><B>GENETIC DISEASES </B></U></A></div> <div> <A HREF="id26.htm" TARGET="_top" TITLE="angelman syndrome"><U><B>angelman syndrome</B></U></A></div> <div> <A HREF="id23.htm" TARGET="_top" TITLE="TAYSACHS DISEASE"><U><B>TAY-SACHS DISEASE</B></U></A></div> <div> <A HREF="id24.htm" TARGET="_top" TITLE="krabbes disease"><U><B>krabbe's disease</B></U></A></div> <div> <A HREF="id25.htm" TARGET="_top" TITLE="Refsums Disease"><U><B>Refsum's Disease</B></U></A></div> <div> <A HREF="id29.htm" TARGET="_top" TITLE="meningitis"><U><B>meningitis</B></U></A></div> <div> <A HREF="id17.htm" TARGET="_top" TITLE="Contact Me"><U><B>Contact Me</B></U></A></div> </td> <td valign="top" height=355 BGCOLOR="#FFFFFF" TEXT="#080000"> <div> DEVELOPMENTAL NEUROLOGIC DISEASES</div> <div> <B><U>NEURAL TUBE FORMATION AND CLOSURE</U></B></div> <bR> <bR> <div> <B>A. Normal Development</B> (1st month)</div> <div> 1. Occurs in first month</div> <div> 2. Notocord and precordal plate differentiate under mesodermal influence</div> <div> 3. Thus, ectoderm is converted to neural tissue.</div> <div> 4. No increase in ectodermal (neurectoderm) cell number, rather change in cell shape</div> <div> 5. Closure of Tube</div> <div> a. Occurs by invagination of neurectoderm.</div> <div> b. First closure point is the medulla (so rarely have isolated openings here)</div> <div> 6. Last closure points are the neuropores:</div> <div> a. Anterior neuropore - closes day 25; brain area</div> <div> b. Posterior neuropore - closes day 27; lower spinal cord</div> <div> 7. Neural crest migration begins within first month</div> <div> a. Sympathetic ganglion</div> <div> b. Dorsal root ganglion</div> <div> c. Schwann cells</div> <div> d. Adrenal Medulla</div> <div> e. Other neuroendocrine cells</div> <bR> <bR> <div> <B>B. Defects</B></div> <bR> <div> 1. Abnormalities in brain and spinal cord will be reflected by superficial changes</div> <div> a. Particularly when abnormal trapping of ectodermal and/or neurectodermal tissue occurs during tube formation and closure</div> <div> b. These "blebs" of tissue may form sacs or other structures, ± nerve tissue</div> <div> 2. Common abnormalities - failed tube formation and/or closure = Dysraphic States</div> <div> a. Occurs in 0.2-0.3% of live births</div> <div> b. Failed tube formation from evagination of neuronal tube area</div> <div> c. Leads to atrophy of exposed CNS tissue</div> <bR> <bR> <div> <B>C. Specific Dysraphic Diseases</B></div> <div> 1. Complete failed tube formation is Craniorachischisis totalis</div> <div> 2. Anencephaly</div> <div> a. Failure to close tube high up</div> <div> b. Medulla intact, so primative responses intact </div> <div> c. Respiration and cardiac control intact</div> <div> 3. Spina bifida cystica - failure to close tube lower down</div> <div> a. Contents of the "Cyst" determine diagnosis:</div> <div> b. Meningocele - no neural elements in cysts</div> <div> c. Meningomyelocele - neural elements in cyst</div> <div> 4. Meningomyelocele</div> <div> a. Sacral nerve invovlement - motor and sensory dysfunction</div> <div> b. Parasympathetic nerve dysfunction - bladder and bowel dysfunction</div> <div> c. Hydrocephalus, usually due to Arnold-Chiari malformation</div> <div> 5. Arnold-Chiari Malformation</div> <div> a. Occurs in ~100% of Meningomyelocele</div> <div> b. Specifically, lower part of brainstem and cerebellum sink below foramen magnum</div> <div> c. Superior and Inferior colliculi fuse - visual auditory malfunction</div> <div> d. Stenosis of the Cerebral Aquaduct occurs leads to hydrocephalus</div> <div> 6. Encephalocele</div> <div> a. Sac in cephalic area, usually filled with brain tissue</div> <div> b. Tissue within sac is usually abnormal</div> <div> c. Occurs more commonly in posterior encephalon than in anterior region</div> <div> 7. Occult (Minimal) Spinal Dysraphism</div> <div> a. Tube abnormally closes, with trapped (neur-) ectodermal tissue</div> <div> b. Typical presentation with Hairy patch, Lipoma (extends in), dimple, neural cyst</div> <div> c. Symptoms include Leg length differences, gait changes, bowel problems</div> <bR> <bR> <bR> <div> <B>SEGMENTATION AND DIVERTICULATION OF NEURAL TUBE (2ND MONTH)</B></div> <bR> <bR> <div> <B>A. Segmentation</B></div> <bR> <div> 1. Single neural tube divides up into various parts or segments</div> <div> 2. Early divisions with later progression</div> <div> a. Prosencephalon: Telencephalon (hemispheres) and Diencephalon</div> <div> b. Mesencephalon: Midbrain</div> <div> c. Rhombencephalon: Metencephalon (Pons and Cerebellum) and Myencephalon (Medulla) </div> <bR> <div> <B>B. Diverticulation</B></div> <bR> <div> 1. Outpouchings of various cephalic structures</div> <div> 2. Dorsal - Pineal Gland</div> <div> 3. Ventral - Neurohypophysis</div> <div> 4. Diencephalon - Optic system, Lateral Geniculate; Olfactory Tract and Bulb</div> <bR> <bR> <div> <B>C. Abnormalities</B></div> <div> 1. Holoprosencephalon</div> <div> a. Failure to split brain into two halves</div> <div> b. Chromosomal defects associated with disease</div> <div> c. Major cerebral function impairment</div> <div> d. Single Ventricle, Cyclops, Cleft Lip</div> <bR> <bR> <div> <B><U>NEURONAL PROLIFERATION & MIGRATION</U></B></div> <bR> <bR> <bR> <div> <B>A. Proliferation</B> (2-4 months)</div> <bR> <div> 1. Intermitotic migration of nerve nuclei (M phase cells close to ventricles)</div> <div> 2. Nearly all neural division occurs near the ventricles</div> <div> a. Basal ganglia is one major exception; develop away from ventricles</div> <div> b. Cerebellar granular cells develop in the external granular layer</div> <div> 3. Hierarchical development occurs as follows:</div> <div> a. Glial cells (small numbers) develop first</div> <div> b. Neurons, larger ones first, smallest last, develop next.</div> <div> c. Glial cells, major wave, develop finally.</div> <bR> <bR> <div> <B>B. Defects</B> in Proliferation</div> <bR> <div> 1. Microcephaly Vera</div> <div> a. Brain looks normal</div> <div> b. Histology shows fewer than normal neuronal cells</div> <div> c. Major intellectual deficits</div> <div> 2. Macrocephaly</div> <div> a. Usually due to an increase number of neural connections</div> <div> b. Can also have increased number of cells</div> <div> c. Range from few symptoms to major deficits</div> <div> d. May be due to reduction of normal levels of nerve cell death during development</div> <bR> <bR> <div> <B>C. Migration</B> (3-5 months)</div> <bR> <div> 1. Glial cells are required before neural migration - lay down a fiber as guide cord</div> <div> 2. Neuronal cells travel up the fibers in columns, then get off at various levels</div> <div> a. Neuronal layers are arranged from 1 (outside layer) to 6 (deepest layer)</div> <div> b. Neurons ascend up this this radial fiber, and stop in layer 6 (lowest) first</div> <div> 3. Astrotactin is a protein made by neural cells to climb up the glial fibers</div> <div> a. Allows ordered climbing along the glial guide cords</div> <div> b. Animal models lacking Astrotactin have random neural cell migration</div> <div> 4. Ordered, normal cell migration is requiered for normal formation of Gyri (and sulci)</div> <div> a. This occurs at 6 months into development</div> <div> b. Failure of normal migration is a major cause of cerebral dysfunction</div> <bR> <bR> <div> <B>D. Cerebellar Maturation</B></div> <div> 1. Main cells in cerebellum are Purkinje Cells and Granular Cells</div> <div> a. Recall cerebellar layers -</div> <div> b. Outside - External Granular Layer - Molecular - Purkinje - Internal Granular</div> <div> 2. Purkinje cells develop around 4th ventricle</div> <div> 3. Granular cells are derived from rhombic lip</div> <div> a. Divide in external granular layer</div> <div> b. Then migrate down from EGL to internal granular layer</div> <bR> <bR> <div> <B>E. Abnormalities</B></div> <bR> <div> 1. Heterotopia - failed normal migration</div> <div> 2. Polymicrogyria - small gyri, fewer neuronal cell layers (eg. 4 instead of 6)</div> <div> 3. Lissencephaly - smooth brain, no Sulci or Gyri.</div> <div> 4. Cerebellar Defects of failed migration</div> <bR> <bR> <div> <B><U>SYNAPTIC FORMATION</U></B></div> <bR> <bR> <div> <B>A. Normal</B> (>6 months of gestation onward)</div> <div> 1. Axons, dendrites, and connections</div> <div> 2. ? of how synapses are formed</div> <div> a. Trophic factors</div> <div> b. Cell Adhesion Molecules (eg. NCAM)</div> <div> c. Role of target cell (post-synaptic cell)</div> <div> 3. Neuronal Cell death</div> <div> a. Dying back</div> <div> b. Increasing numbers of targets decreased nerve cell death</div> <div> 4. Synapse Formation - Recent data indicate that at least in some systems, post-synaptic transmitter receptors are present before axons reach the synapse area</div> <div> 5. Synaptic changes occur during development and for years after birth</div> <bR> <bR> <div> <B><U>DEGENERATIVE DISEASES</U></B></div> <bR> <bR> <div> <B>A. Organelle Dysfunction</B></div> <bR> <div> 1. Mitochondria</div> <div> 2. Peroxisomes</div> <div> 3. Lysosomes</div> <div> 4. Cytosolic Enzymes</div> <bR> <bR> <div> <B>B. Stored Material</B></div> <bR> <div> 1. Sphingolipid</div> <div> 2. Glycogen</div> <div> 3. Mucopolysaccharides</div> <div> 4. Lysosomal enzymes (note targetting with mannose-6-phosphate)</div> <bR> <div> <B>C. Lysosomes</B></div> <bR> <div> 1. Required for removal of stored substances</div> <div> 2. Especially for ganglioside degradation</div> <div> a. GM2 accumulation leads to Tay-Sach's Disease</div> <div> b. Gaucher's Disease</div> <bR> <div> <B>D. Pathologic Changes in Lysosomal Storage Diseases</B></div> <bR> <div> 1. May occur in Grey Matter: Cell ballooning, full of stored material</div> <div> 2. Axonal (White Matter): degeneration of axons</div> <bR> <div> <B>E. Symptoms</B></div> <bR> <div> 1. Depend on whether Grey or White Matter, or both, are affected</div> <div> 2. Grey Matter</div> <div> a. Delayed Psychomotor Development</div> <div> b. Adult Dementia</div> <div> c. Seizures Prominant</div> <div> d. Retinal Cherry Red spots</div> <div> e. Ataxia</div> <div> 3. White Matter</div> <div> a. Upper Motor Neuron: Spasticity, Hyperreflexia, Babinsky</div> <div> b. Polyneuropathy</div> <div> c. Optic Nerve Atrophy</div> <div> d. Ataxia</div> <div> e. Decreased Intelligence</div> <div> f. Seizures</div> <bR> <bR> <div> <B>F. Dysmyelinating Disease</B></div> <bR> <div> 1. Trouble forming or maintaining axons</div> <div> 2. Myelin synthesis requires proteins and many complex lipids</div> <div> 3. Sulfatases also required for metabolism (degradation) of compounds</div> <div> 4. Galactocerebrosidase deficiency = Krabbe's Disease</div> <bR> <bR> <div> <B>G. Krabbe's Disease</B> </div> <div> 1. Missing Galactocerebrosidase</div> <div> 2. Presence of globoid cells on pathology - macrophages ingesting dead cells</div> <div> 3. Much decreased numbers of oligodendrocytes</div> <div> a. This apparently due to accumulation of toxin called psychosine</div> <div> b. This is normally degraded by galactocerebrosidase</div> <bR> <bR> <div> <B>H. Neuronal Malfunction in Storage Diseases</B></div> <div> 1. Filled cells simply overstuffed, cannot function</div> <div> 2. Altered nerve conduction properties</div> <bR> <bR> </td> </tr></table></body>