PATHOLOGY 4

<body topmargin=0 leftmargin=0 marginheight=0 marginwidth=0> <table cellpadding=0 cellspacing=0 border=0><tr> <td valign="top" colspan=2 height=22 BGCOLOR="#FFFFFF" TEXT="#080000" bgproperties="fixed" background="041000d2egerdp.gif"> <div> </div> </td> </tr><tr> <td valign="top" width=145 BGCOLOR="#333399" TEXT="#080000" background="040a2c00erkjzj.gif"> <div> <IMG SRC="13130400.gif" border=0 width="48" height="64" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="133786c0.gif" border=0 width="120" height="108" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="13090850.gif" border=0 width="144" height="133" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </td> <td valign="top" height=458 BGCOLOR="#FFFFFF" TEXT="#080000"> <div> <FONT SIZE="5" COLOR="#336600" FACE="Times New Roman" ><I>NEUROPATHOLOGY</I></FONT><FONT SIZE="1" COLOR="#663399" FACE="Times New Roman" >    </FONT> |    <B> </B><FONT SIZE="2" COLOR="#0000BF" FACE="Times New Roman" ><A HREF="index.htm" TARGET="_top" TITLE="NEUROPATHOLOGY"><U><B>home</B></U></A></FONT></div> <div> <A HREF="id18.htm" TARGET="_top" TITLE="HISTOLOGY REVIEW"><U>HISTOLOGY REVIEW</U></A>   |   <A HREF="id19.htm" TARGET="_top" TITLE="PHYSIOLOGY REVIEW"><U>PHYSIOLOGY REVIEW</U></A>   |   <A HREF="id20.htm" TARGET="_top" TITLE="PATHOLOGY part1"><U>PATHOLOGY part1</U></A>   |   <A HREF="id22.htm" TARGET="_top" TITLE="pathology part2"><U>pathology part2</U></A>   |   <A HREF="id26.htm" TARGET="_top" TITLE="PATHOLOGY3"><U>PATHOLOGY3</U></A>   |   <B>PATHOLOGY 4</B>   |   <A HREF="id21.htm" TARGET="_top" TITLE="PICTURES"><U>PICTURES</U></A>   |   <A HREF="id31.htm" TARGET="_top" TITLE="tumor gn"><U>tumor gn</U></A>   |   <A HREF="id30.htm" TARGET="_top" TITLE="multiple sclerosis"><U>multiple sclerosis</U></A>   |   <A HREF="id24.htm" TARGET="_top" TITLE="quiz"><U>quiz</U></A>   |   <A HREF="id23.htm" TARGET="_top" TITLE="quizanswer"><U>quizanswer</U></A>   |   <A HREF="id17.htm" TARGET="_top" TITLE="Contact Me and links"><U>Contact Me and links</U></A>   |   <A HREF="id29.htm" TARGET="_top" TITLE="info and news"><U>info and news</U></A></div> <div> <IMG SRC="04207040.gif" border=0 width="263" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <B>PATHOLOGY 4</B></div> <DIV ALIGN="LEFT"></DIV> <div> <IMG SRC="1326ec80.gif" border=0 width="110" height="200" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <bR> <bR> <bR> <div> <FONT SIZE="3" COLOR="#000000" FACE="Verdana" >CEREBRAL ISCHEMIA AND STROKE</FONT> [ <A NAME="pictures"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>PICTURES ARE IN THE PICTURE AREA IN THIS WEB]</div> <div> <B><U>HYPOXIC-ISCHEMIC ENCEPHALOPATHY </U></B></div> <div> <B><U>STROKE</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B><U>CEREBRAL INFARCTS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HEMORRHAGIC INFARCT</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">LACUNAR INFARCT</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CAUSES OF ISCHEMIC INFARCTION</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">VENOUS INFARCT</U></B></div> <div> <B><U>INTRACEREBRAL AND SUBARACHNOID HEMORRHAGE</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HYPERTENSIVE INTRACEREBRAL HEMORRHAGE</U></B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ARTERIAL ANEURYSMS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ARTERIOVENOUS MALFORMATIONS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">OTHER CAUSES OF HEMORRHAGIC STROKE</U></B></div> <bR> <div> <B><U>HYPOXIC - ISCHEMIC ENCEPHALOPATHY</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <div> <B><U>GENERAL PRINCIPLES </U></B></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The brain is about two percent of the total body mass but consumes 15 percent of the energy generated in the body. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most of this energy is used by neurons to maintain ionic gradients that are important for conductivity and synaptic function.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Some energy is also needed to support synthetic and catabolic activity in neurons and glial cells and, in young age, for growth.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Energy for these functions is derived from hydrolysis of ATP.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Thus, the brain is like a chemical battery of ATP which must be constantly recharged. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The brain has no energy stores of its own except for a small amount of glycogen in astrocytes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Anaerobic glycolysis of this glycogen is insufficient to meet energy needs. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fatty acids cannot be used because they are not transported across brain capillaries.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> There is no back up high energy phosphate such as creatine phosphate in brain cells.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Consequently, energy for recharging the ATP battery is derived exclusively from oxidative phosphorylation of glucose. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The brain depends on a second by second supply of oxygen and glucose by the blood.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <B>A drop in cerebral perfusion, hypoxia, protracted hypoglycemia and severe anemia</B> can cause a critical shortage of energy (<B>energy crisis</B>) .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In protracted <B>generalized seizures</B>, neurons use up glucose and oxygen faster than they are supplied, with the same result.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The most common cause of energy crisis is a drop of cerebral perfusion (global ischemia). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Blood glucose levels below 30 mg/dl for 10-20 minutes and seizures lasting 1-2 hours also cause permanent brain damage. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pure hypoxia in clinical settings is unusual. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Patients with lung disease are treated with oxygen and the brain can adapt to pure hypoxia, especially if it develops slowly.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Hypoxia develops acutely in CO poisoning, which displaces oxygen from hemoglobin. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Unlike hypoxia, hypoglycemia, and seizures, global ischemia causes not only energy failure but results also in accumulation of lactic acid and other toxic metabolites that are normally removed by the circulation. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The most common clinical causes of hypoxic-ischemic encephalopathy (HIE) are cardiac arrest and severe hypotension (shock).</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The mechanism of neuronal damage in HIE is now beginning to be understood. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Obviously, lack of energy initially causes electrical failure and, if it lasts long enough, an arrest of all cellular functions and cell death.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> However, animal experiments and clinical studies suggest that the ischemic insult alone is not always enough to kill neurons.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Even sublethal HIE can set in motion a series of toxic reactions that finish off injured neurons and kill additional ones that have not been damaged during the initial insult. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Thus, following global ischemia, neurons do not die suddenly or all at once.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In some of them, damage develops hours or days after the insult.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Most neurons undergo necrosis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In some neurons, HIE triggers an apoptosis-like process.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The first result of energy depletion is failure of Na<FONT SIZE="1" COLOR="#000000" FACE="Verdana" >+</FONT>-K<FONT SIZE="1" COLOR="#000000" FACE="Verdana" >+</FONT> pumps leading to <B>depolarization</B> of the neuronal membrane. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Synaptic function and conductivity are lost at this point but neuronal structure is intact. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Structural damage develops as a result of <B>Ca</B><FONT SIZE="1" COLOR="#000000" FACE="Verdana" ><B>++</B></FONT><B> influx</B> into neurons. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This influx results from opening of voltage-gated Ca<FONT SIZE="1" COLOR="#000000" FACE="Verdana" >++</FONT> channels (due to depolarization) but, more important, from the action of <B>glutamate</B>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Depolarization causes neurons to release the excitatory neurotransmitter glutamate (because of its toxic action in HIE glutamate is also called <B>excitotoxin</B>). </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The NMDA and AMPA receptors of glutamate are channels that are permeable Ca</B><FONT SIZE="1" COLOR="#000000" FACE="Verdana" ><B>++</B></FONT><B>. Activation of these receptors causes influx of Ca</B><FONT SIZE="1" COLOR="#000000" FACE="Verdana" ><B>++ </B></FONT><B>into neurons. Ca</B><FONT SIZE="1" COLOR="#000000" FACE="Verdana" ><B>++</B></FONT><B> activates </B><B>catabolic enzymes</B><B> (proteases, phospholipases, endonucleases). Ca</B><FONT SIZE="1" COLOR="#000000" FACE="Verdana" ><B>++ </B></FONT><B>also activates NO synthase, resulting in NO and </B><B>free radical</B><B> production.</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Additional free radicals result from the general impairment of oxidative phosphorylation.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Free radicals and Ca<FONT SIZE="1" COLOR="#000000" FACE="Verdana" >++</FONT> activated catabolic enzymes destroy structural proteins, membrane lipids, nucleic acids and other cellular contents causing neuronal necrosis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">DNA damage from endonucleases also triggers autodestructive cellular processes (apoptosis).<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Incomplete combustion of glucose results in <B>lactic acidosis</B>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Lactic acid can get through cell membranes and can damage not only neurons but glial and mesenchymal cells as well.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Additionally, lactic acid and hydrogen ions cause cerebral edema by attracting water. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Obviously, lactic acidosis is more severe in patients with HIE who are hyperglycemic and is not a significant factor in hypoglycemic encephalopathy or seizures.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B><U>Cerebral edema</U></B><B><U> </U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">in HIE is due to vascular injury and the release in the interstitial space of vasoactive metabolites such as arachidonic and other fatty acids (derived from membrane glycerolipids), lactic acid, electrolytes and other unknown osmoles. Arachidonic acid also has a chemotactic function and induces acute inflammation.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Free radicals, lactic acid, cerebral edema, and inflammation cannot develop in unperfused, completely ischemic tissue. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They develop following <B>reperfusion</B>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Thus, reperfusion is a double-edged sword. Without it, there is no hope for recovery. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">On the other hand, reperfusion following a critical level of injury is responsible for the aggravation of the pathology and continuing nerve cell loss following the initial insult. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">By the same token, knowledge of the various aspects of HIE and reperfusion injury may suggest possible neuroprotective interventions.</div> <div>  </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">With this background, let us examine what happens with different grades of HIE.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Suppose that someone has a brief episode of global ischemia, say from fainting. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Within seconds, energy failure causes electrical activity in neurons to cease and the patient loses consciousness.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Neurons and glial cells are viable and if circulation is promptly restored, the patient returns to normal.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> If, however, ischemia lasts longer, first the integrity of cell membranes will be compromised and then cellular metabolism will cease and neurons will die. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Ischemia lasting 4-5 minutes can damage irreversibly hippocampal and neocortical pyramidal cells, striatal neurons and Purkinje cells.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> More protracted ischemia can damage thalamic and brainstem neurons.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> If a patient dies shortly after the insult, the brain is usually grossly and microscopically normal. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If the patient survives (usually on the respirator) for some time but cerebral perfusion is not restored, the brain autolyzes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> If the patient survives after a severe insult and perfusion is restored, changes begin to appear within hours.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> At first, injured neurons shrink and become eosinophilic.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This is due to increased density of damaged mitochondria. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Neuronal nuclei become dense. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The shrunken eosinophilic neuron (which is referred to as <B>anoxic neuron</B>) is the hallmark of HIE. Astrocytes swell (Alzheimer type II cells). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This is a poorly understood response of astrocytes to metabolic insults. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If the patient survives longer, damaged neurons disintegrate and are removed by macrophages.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> With time, cortical atrophy and gliosis develop. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In an ironic sense, the brain has to be alive in order for the changes of neuronal death to develop. Reperfusion causes additional (delayed) neuronal injury, brings monocytes to the site of injury and sustains the glial and vascular reactions that follow.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Some cases of HIE, usually after brief insults, cause neuronal death only without damage of glial cells (<B>selective neuronal necrosis</B>).</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Among neurons, the hippocampal pyramidal cells of CA1, pyramidal neocortical neurons (layers 3, 5, and 6), Purkinje cells and striatal neurons are most vulnerable. </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There is also a regional variation in susceptibility to HIE. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The cerebral cortex and striatum are more sensitive than the thalamus and the thalamus in turn is more sensitive than the brainstem. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The spinal cord may remain uninjured even when all the rest of the CNS is severely damaged. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The single most likely explanation for this <B>selective vulnerability</B> is excitotoxicity (glutamate toxicity) which affects only neurons. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Additionally, neurons are more vulnerable than glial cells because they consume more energy. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There are differences in neurotransmitter patterns and energy metabolism among different classes of neurons.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> For example, in hypoglycemia, Purkinje cells are not affected because they have a more efficient glucose transport system. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In severe cases of HIE, not only neurons but glial cells are damaged as well. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The key factor that converts selective neuronal necrosis to total tissue necrosis is probably lactic acidosis.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><U> <A NAME="pathhie"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>THE PATHOLOGY OF HYPOXIC-ISCHEMIC ENCEPHALOPATHY</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The most common pattern of injury in HIE is <B>selective neuronal loss</B> of sensitive neurons (pyramidal cells of CA1 of the hippocampus and layers 3, 5 and 6 of the neocortex, Purkinje cells and striatal neurons).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <B>Bilateral hippocampal damage </B> causes <B>Korsakoff amnesia. </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This is a memory disorder characterized by inability to retain new information (anterograde amnesia) and a less severe defect of recall of old memories (retrograde amnesia).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Diffuse cortical or thalamic neuron loss (with intact brainstem) results in dementia or the <B>vegetative state</B> (loss of cognitive functions and emotion with preservation of sleep-wake cycles, autonomic function, and breathing).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> With more protracted ischemic insults, all cortical neurons and glial cells may be damaged and the injury may involve the brainstem. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Such brains develop severe <B>edema</B>. <B>Brain death</B> is a terminal clinical state characterized by <B>loss of cerebral and</B> <B>brainstem</B> function. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The clinical criteria for brain death are complete unresponsiveness, absence of brain stem reflexes, electrical silence (flat EEG), and absence of cerebral perfusion. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The latter is a terminal event, probably due to blockage of capillaries from endothelial swelling and cerebral edema. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Brain death can be distinguished clinicallly from the vegetative state and other conditions that cause severe brain damage and coma.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In most cases, brain death leads to loss of vital functions.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Therefore, for legal purposes, brain death is the equivalent of somatic or cardiorespiratory death.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If, following a hypoxic-ischemic insult, intracranial pressure is high and arterial pressure is low, cerebral perfusion does not resume. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If such a patient is put on the respirator, the brain (under normal body temperature) undergoes an enzymatic autodigestion which may end in liquefaction. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The term "<B>respirator brain</B>" that has been applied in such cases is misleading because the autolysis is not caused by the respirator. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The term "non-perfused brain" is more accurate. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Because circulation is arrested and all metabolic activity ceases, the non-perfused brain does not show any reactive changes (inflammation, macrophages, gliosis), just autolysis.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Imaging reveals hypodensity, due to edema and loss of tissue density, without enhancement</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <FONT SIZE="3" COLOR="#000000" FACE="Verdana" >Because the main or final event in most HIE cases is cardiac arrest, it is usually not possible to distinguish ischemic, hypoxic or hypoglycemic encephalopathy from one another except in a few cases.</FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> For instance, bilateral hippocampal neuron loss and gliosis (<B>hippocampal sclerosis</B>) without other lesions is seen in some patients with epilepsy or following cardiac arrest of short duration.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sparing of Purkinje cells suggests hypoglycemic encephalopathy. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In addition to causing hypoxia, CO binds to iron-rich neurons of the globus pallidus and substantia nigra selectively damaging these nuclei.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In some instances, global ischemia causes bilateral, symmetric cerebral infarcts in the border zones between major arterial territories.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Rarely, HIE involves the white matter, causing myelin damage and loss.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Unravelling of damaged myelin results in vacuolization and a spongy appearance of the white matter in tissue sections. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">White matter damage is common in CO poisoning but may occur with other forms of HIE.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><U> <A NAME="stroke"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>STROKE</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Stroke (cerebrovascular accident) is a sudden neurological deficit. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Strokes are caused either by occlusion of cerebral blood vessels leading to ischemic necrosis of the brain (cerebral infarction) or by rupture of blood vessels resulting in hemorrhage in the brain or in the subarachnoid space. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Eighty percent of strokes are occlusive and 20 percent are hemorrhagic. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The fatality rate of intracerebral and subarachnoid hemorrhage is much higher than that of cerebral infarction.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Stroke accounts for about 50 percent of neurological problems in a general hospital.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It is the third most common cause of death after heart disease and cancer. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In recent years, there has been a steady decline in the incidence of stroke, due, in large part, to better control of hypertension.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><U> <A NAME="infarcts"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>CEREBRAL INFARCTS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <bR> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A </U></B><B><U>transient ischemic attack (TIA)</U></B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">is a focal neurological deficit that lasts less than 24 hours. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It is usually caused by an embolus that breaks up soon after it lodges.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Neurological function is restored and there is no permanent tissue damage.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Cerebral infarction is focal brain necrosis due to complete and prolonged ischemia that results in necrosis of all tissue elements, neurons, glia and vessels.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Lysis of an occluding thrombus or embolus may result in reperfusion of some infarcts after necrosis has occurred. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Other infarcts are never reperfused. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The basic molecular mechanisms of cell and tissue injury that were discussed under HIE apply also to infarcts. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">One additional concept, the <B>ischemic penumbra</B>, is worth stressing. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In every infarct, there is a central core of total ischemia and total tissue necrosis which is irreversible.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This area is surrounded by a zone of borderline ischemic tissue, the ischemic penumbra, which receives collateral circulation.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Ischemia in the penumbra is severe enough to cause electrical failure but not so severe to result in irreversible structural damage. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Prompt restoration of circulation in the penumbra by injection of thrombolytic agents may prevent structural damage in this area, thus limiting the neurological deficit. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Ischemic stroke is an emergency. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The window of opportunity for salvaging the penumbra is very short.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> If adequate blood supply is not restored within 3 to 4 hours, the penumbra merges with the necrotic core.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The release of osmotically active substances (arachidonic acid, electrolytes, lactic acid) from the necrotic brain tissue causes <B>cerebral edema.</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This is aggravated by vascular injury and leakage of proteins in the interstitial space. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">By 3-4 days, large amounts of interstitial fluid accumulate in the infarct and around it.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B>This is </B><B>the most dangerous period for a large cerebral infarct.</B><B> Death from a massive hemispheric infarct is caused by cerebral edema and herniations, not by the loss of brain tissue. As edema subsides, neurological function improves and the neurological deficit "contracts".</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <bR> <bR> <div> <B><U> <A NAME="pathinfarcts"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>PATHOLOGY OF ISCHEMIC INFARCTS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In the first day or so, the infarct appears as a poorly demarcated area of <B>softening</B>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Imaging at this stage may be entirely negative, especially in brain stem infarcts.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> At the peak of edema, the infarct appears hypodense and bright on T2 MRI images. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The infarcted tissue becomes sharply demarcated and softens progressively. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">From the second week onward, it begins to <B>disintegrate</B> and is gradually replaced by a cavity.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The size and location of infarcts follows the anatomy of vascular territories<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT>and produces characteristic anatomical and clinical patterns, especially in brainstem infarcts.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B>Microscopical examination</B> in the first 24 to 48 hours reveals<FONT SIZE="3" COLOR="#000080" FACE="Verdana" ><B> </B></FONT><B>anoxic neurons </B>, pallor of staining and vacuolization of the white matter due to unraveling of myelin, and<B>axonal swellings</B><FONT SIZE="3" COLOR="#000080" FACE="Verdana" ><B>.</B></FONT><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">During the first week, there is a transient inflammatory reaction, especially around blood vessels and in the meninges, due to release of arachidonic and other fatty acids. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">As the core of infarcted area disintegrates, endothelial cells from the periphery proliferate and capillaries grow into the dead tissue. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Neovascularization</B> (which accounts for contrast enhancement) peaks at 2 weeks.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mononuclear cells from the blood stream enter the infarct through damaged vessels. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They ingest the products of degradation of neurons and myelin and are transformed into <B>lipid-laden macrophages </B>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Macrophage reaction appears early and peaks at 3-4 weeks. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Astrocytes from the surrounding undamaged brain proliferate and form a <B>glial scar </B>around the infarct </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This is completed in approximately 2 months. After that, the infarct remains unchanged. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">With maturation of new capillaries and glial scar formation, the blood brain barrier is once again sealed.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Neurons do not regenerate.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> So, some brain tissue is lost forever.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <bR> <div> <B> <A NAME="hgicinfarct"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B>A hemorrhagic infarct</B> is an infarct stippled with petechiae or showing confluent larger hemorrhages, especially in necrotic gray matter.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The blood leaks from collateral vessels or through necrotic capillaries when the occluding thrombus or embolus break up and the infarcted area is reperfused.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Hemorrhagic infarcts are most common in embolism. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Use of thrombolytics or anticoagulants may convert a bland infarct into a hemorrhagic one.</div> <bR> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" > <A NAME="lacunar_infarct"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></FONT><B>Lacunar infarcts</B> are small infarcts in the deeper parts of the brain (basal ganglia, thalamus, white matter) and in the brain stem.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They are responsible for about 20 percent of all strokes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They are caused by occlusion of deep penetrating branches of major cerebral arteries and are particularly common in <B>hypertension</B> and <B>diabetes</B>, which are associated with severe atherosclerosis of small vessels.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> A small lacunar infarct (e.g., one involving the internal capsule) may cause as severe a neurologic deficit as a much larger hemispheric infarct but without the life-threatening cerebral edema that is seen in the latter.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><U> <A NAME="causes"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>CAUSES OF ISCHEMIC INFARCTION.</U></B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The types of vascular disease that cause cerebral infarction are diverse. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The vast majority of infarcts are caused by <B>atherosclerosis</B> of large arteries,<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT>alone or with superimposed thrombosis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hypertension and diabetes induce a change in small arteries and arterioles referred to as <B>"small vessel disease"</B>, "small artery arteriosclerosis", <B>"hyaline atreriolosclerosis"</B>, and "lipohyalinosis."<FONT SIZE="3" COLOR="#FF0000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This angiopathy is characterized by loss of smooth muscle and an increase in extracellular matrix.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These changes cause vessels to be less elastic and more fragile.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Their walls thicken and become homogeneous and hyaline (glassy) in H&E stains, and their lumina narrow.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Atherosclerosis and small vessel disease account for nearly half of all cerebral infarcts. </div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Embolism</U></B><B> </B>accounts for approximately one third. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most emboli are fragments of blood clots that originate in the heart or major vessels. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Conditions causing cardiac emboli include </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">myocardial infarcts, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">atrial fibrillation and </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">other arrhythmias, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">rheumatic heart disease,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> bacterial and non-bacterial endocarditis,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> prosthetic valves, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mitral valve prolapse, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">atrial myxoma, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">calcified mitral annulus and </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cardiomyopathy. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">An embolus cannot be distinguished grossly or microscopically from a locally formed thrombus.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> An infarct is assumed to be embolic if it is hemorrhagic, there is a source of emboli, there are multiple infarcts of the brain and other organs (kidney, spleen), and there is no atherosclerosis or other vascular disease. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Some emboli consist of atheromatous material that is detached from ulcerated atherosclerotic plaques of the aorta or carotid arteries. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Vascular manipulation (angiography, carotid endarterectomy) may cause atheromatous embolism.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Rarer causes of embolism are fat, air, and tumor emboli.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B><U>Other causes of arterial occlusion and infarction include:</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Vasculitis</B> - </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polyarteritis nodosa,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <B>giant cell (temporal) arteritis,</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">granulomatous arteritis, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Takayasu disease (idiopathic aortitis), </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">systemic lupus erythematosus, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">infectious vasculitis (bacterial endocarditis, pyogenic meningitis, tuberculous meningitis, CNS syphilis, fungal vasculitis.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B><U>Hematologic disorders -</U></B><U> </U></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polycythemia, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hemoglobinopathies (sickle cell disease), </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">deficiencies of anticoagulant factors,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> thrombotic thrombocytopenic purpura.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B><U>Metabolic disorders </U></B><U>- </U></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Dyslipoproteinemias,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Fabry disease, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">homocystinuria and homocysteinemia,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> organic acidemias, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mitochondrial disorders.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Some of these conditions cause ischemic infarcts even in children and infants. Mitochondrial disorders can cause TIAs and ischemic strokes.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B><U>Hereditary hypercoagulability disorders-</U></B><U> </U></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Factor V Leiden, Prothrombin 20210A, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Methylenetetrahydrofolate reductase A223V. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These polymorphisms derange the delicate balance between natural anticoagulant and procoagulant pathways.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They are very prevalent in the population and combine with one another and with aquired conditions that promote clotting, causing venous and arterial infarcts.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><U>Trauma</U></B> to Head and Neck can cause dissecting aneurysms and other lesions of the carotid and vertebral arteries. </div> <div> The pattern of brain necrosis in severe trauma often suggests vascular occlusion.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B><U>Contraceptives</U></B><B> </B>and estrogen therapy cause most commonly venous thrombosis and rarely intimal hyperplasia and thrombosis of cerebral and extracerebral arteries.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B>Vascular Spasm. </B>This is a complication of subarachnoid hemorrhage.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B><U>Miscellaneous</U></B><U> -</U></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Spontaneous dissecting aneurysms,<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">moya-moya disease (narrowing of proximal cerebral arteries), </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">amyloid angiopathy,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> cerebral autosomal dominant angiopathy with strokes and leukoencephalopathy (CADASIL).<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B> <A NAME="venous"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B><U>VENOUS INFARCT</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><U> </U></FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Thrombosis of venous sinuses and their tributaries causes congestion, hemorrhage and necrosis of brain tissue (venous infarction).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Venous infarcts from thrombosis of the superior sagital sinus are parasagital.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The causes of venous thrombosis are diverse and include </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">oral contraceptives, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">inherited deficiencies of anticoagulant factors, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cancer and,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> in infants, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">dehydration.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B> <A NAME="hgicstroke"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B><U>HEMORRHAGIC STROKES</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <div> <B><U>(INTRACEREBRAL AND SUBARACHNOID HEMORRHAGE)</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <div> Approximately 20 percent of strokes are due to rupture of blood vessels with intracerebral or subarachnoid hemorrhage. </div> <div> The three major causes of hemorrhagic stroke are</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> hypertensive intracerebral hemorrhage,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> ruptured arterial aneurysms,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> and arteriovenous malformations. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Intracerebral and subarachnoid hemorrhage are also very common in head trauma.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <bR> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" > <A NAME="hypertensive"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></FONT><B><U>HYPERTENSIVE INTRACEREBRAL HEMORRHAGE.</U></B><B> </B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This hemorrhage results from rupture of small, penetrating arteries.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Hypertensive angiopathy (small vessel disease) stiffens vessel walls and makes them fragile. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This, in conjunction with increased luminal pressure, causes vascular rupture and hemorrhage. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The most frequent sites of hypertensive intracerebral hemorrhage are t<FONT SIZE="3" COLOR="#FF0000" FACE="Verdana" ><B>he basal ganglia and thalamus.</B></FONT><FONT SIZE="3" COLOR="#FF0000" FACE="Arial" ><B> </B></FONT></div> <bR> <bR> <div> <B>Less commonly</B>, hypertensive intracerebral hemorrhage involves <B>the cerebellum and the pons</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> and occasionally the subcortical white matter</div> <div>  Large intracerebral hemorrhages cause increased intracranial pressure and carry a high fatality rate. </div> <bR> <div> Improved control of hypertension in the last 20 years has led to a dramatic reduction in the incidence of hypertensive intracerebral hemorrhage.</div> <bR> <div>  </div> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" > <A NAME="arterial_aneurysms"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></FONT><B><U>ARTERIAL ANEURYSMS.</U></B><B> </B></div> <div> Saccular or "berry" aneurysms develop in the walls of major cerebral arteries at branching points, where the media and internal elastica are discontinuous. </div> <div> The majority of them are on the <B>circle of Willis </B>and the first bifurcation of the middle cerebral artery.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They are multiple in 20 percent of the cases. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Nonruptured aneurysms are seen in two percent of adult autopsies.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Berry aneurysms occur with increased frequency in patients with hypertension, coarctation of the aorta, and polycystic kidney disease.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Large saccular aneurysms can cause symptoms by compressing cranial nerves, vessels, and brain tis</B>sue.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The vessels bearing the aneurysms are in the subarachnoid space. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Consequently, rupture of such aneurysms causes <B>subarachnoid hemorrhage.</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Blood spurts out of the ruptured aneurysm with a force that can tear the soft brain. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If the stream of blood is directed toward brain, the aneurysmal bleed may cause intracerebral and intraventricular hemorrhage.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The clinical hallmark of subarachnoid hemorrhage from a ruptured aneurysm is a<B> sudden severe headache</B> without focal neurologic deficits. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A massive aneurysmal bleed raises <B>intracranial pressure</B> to levels of arterial pressure, resulting in arrest of cerebral perfusion, unconsciousness and HIE. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Approximately one week after the bleed, <B>vascular spasm</B> of major cerebral arteries develops, causing additional ischemia.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The pathogenesis of spasm is not understood. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It is associated with clots developing around cerebral arteries.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Later, <B>hydrocephalus</B> may develop due to blockage of CSF flow by subarachnoid clots and from meningeal fibrosis which results from their organization.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B><U>Fusiform aneurysms</U></B><B><U> </U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">are vascular dilatations due to atherosclerosis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They are seen most commonly in the basilar artery and are associated with thrombosis and brainstem infarction and less frequently with rupture and subarachnoid hemorrhage.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div>  <A NAME="arteriovenous_malformations"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></div> <bR> <div> <B><U>ARTERIOVENOUS MALFORMATIONS. </U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Arteriovenous malformation (AVM) is a developmental abnormality of cerebral vessels. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It consists of a tangle of abnormal vessels interposed between a feeding artery and a draining vein.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Most AVMs are in the distribution of the middle cerebral artery but they may occur anywhere.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In addition to classical AVMs, there are several other related types of vascular anomalies and hamartomas that cause similar manifestations. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The abnormal vessels may be in brain tissue, in the subarachnoid space, or both.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">AVMs and other vascular anomalies cause seizures and neurologic deficits due to chronic compression and ischemia of brain tissue.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Their most feared outcome is <B>intracerebral and subarachnoid hemorrhage.</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There may be multiple episodes of bleeding over many years (sometimes since childhood), manifested by headaches, a single catastrophic bleed, or both. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Patients with AVMs also have an increased incidence of aneurysms.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" > <A NAME="other_causes"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></FONT><B><U>OTHER CAUSES OF HEMORRHAGIC STROKE.</U></B><B> </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Less frequently, intracerebral and subarachnoid hemorrhage is caused by </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cerebral angiitis</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">(polyarteritis nodosa, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">granulomatous arteritis,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> SLE, bacterial arteritis) </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cerebral amyloid angiopathy.</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hardening of cerebral vessels due to deposition of amyloid in their walls often causes multiple hemorrhages, especially in the subcortical white matter (<B>lobar hemorrhages</B>).<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Amyloid angiopathy occurs in sporadic and familial settings. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The best known familial form (hereditary cerebral hemorrhage with amyloidosis - Dutch type) is caused by a mutation of the <B>amyloid precursor protein</B> gene on chromosome 21. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Other angiopathies</B>(Ehlers-Danlos syndrome, homocystinuria, amphetamine vasculitis) and genetic or acquired coagulopathies and platelet disorders may also cause hemorrhagic strokes.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><U>Hemorrhagic stroke (SPONTANEOUS INTRACRANIAL HEMORRHAGE)</U></B><U> </U></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Traumatic extradural, subdural and intracranial hemorrhages  are three major categories. </div> <div> 1. INTRACEREBRAL hemorrhage</div> <div> 2. SUBARACHNOID hemorrhage</div> <div> 3. INTRA-EXTRACEREBRAL (MIXED) hemorrhage - a form of hemorrhage involving both the parenchyma and subarachnoid space </div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The task of the clinician is to differentiate these types of hemorrhage, as they have different aetiologies, and the CT scan is particularly useful in this regard. </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CT features of intracranial hemorrhage: As extravasated blood undergoes liquefaction and absorbtion, changes occur in its CT appearances.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> One can separate an acute stage of hemorrhage (0-2 days: hyperdense),</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> from a subacute stage (3-14 days: isodense) and a chronic stage (>14 days - hypodense).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In intracerebral hemorrhage liquefaction proceeds from the periphery to the centre, and is accompanied by hypodense perifocal oedema. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">With intravenous contrast medium, the hyperaemic (vascularised) margin of the hematoma cavity shows enhancement. </div> <bR> <bR> <div> <B>1. Intracerebral (intraparenchymal) hemorrhage:</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These hemorrhages may be further subdivided, and the most important question that needs to be answered is - "is the hemorrhage ganglionic or lobar", as the site of the bleed is indicative of the underlying pathology. </div> <div> a). <B><U>Ganglionic region hemorrhage</U></B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">is almost invariably associated with hypertensive arteriolosclerosis affecting the small penetrating, lenticulo-striate vessels, and is the most common cause of death among cerebrovascular diseases. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most of these bleeds are of a large size and often rupture into the ventricle (haemato-hydrocephalus), resulting in rapid death. (Approximately 20 % of hypertensive intracerebral hemorrhages occur in either the cerebellum or brain stem (pontine tegmentum). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Frequently at autopsy, the brains of hypertensive patients also exhibit small orange-yellow slit-like lesions (slit hemorrhages) at the junction of cortex and white matter, or in the basal ganglia.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These represent the scars of old circumscribed small hemorrhages. (They have to be differentiated from lacunes which are small infarcts occurring in the deep grey, and base of the pons, in hypertensive individuals, and are due to lipohyalinosis of arterioles (see above). </div> <bR> <div> b). <B><U>Lobar hematomas</U></B> -</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These types of hemorrhage are usually caused by rupture of an arterio-venous malformation (AVM) or angioma.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> However, if the hematoma is present in the frontal or medial temporal lobes, a ruptured berry aneurysm (see below) should also be considered in the differential diagnosis.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Lobar hematomas may also occur in association with certain primary brain tumours, notably oligodendroglioma, or metastases (choriocarcinoma & melanoma), in which case they are often associated with extension into the subarachnoid space (intra-extracerebral (see below). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hemorrhages due to blood dyscrasia (eg. in association with leukaemia or lymphoma) are also frequently lobar and may occur at any site.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They are of variable size and are often multifocal. </div> <bR> <bR> <div> <B><U>2. Subarachnoid hemorrhage:</U></B><U> </U></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Major subarachnoid hemorrhage is most commonly caused by rupture of a berry aneurysm, usually situated at the junction of the MCA/PcomA, or ACA/AcomA. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The exact etiology of these aneurysms is unclear but they are basically developmental in nature. (As already mentioned, anterior aneurysms may rupture into the adjacent brain and ventricles, producing the characteristic CT image of an inter-hemispheric/frontal lobe hematoma and intraventricular clot). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Although infrequent, it should also be remembered that a ruptured berry aneurysm is also the commonest cause of a spontaneous subdural hemorrhage. </div> <bR> <div> <B><U>3. Intra-extracerebral (mixed) hemorrhage</U></B><B>:</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These hemorrhages can be defined by CT and will have the clinical features common to SAH and lobar hemorrhage. The hematoma is usually peripheral and may be associated with a relatively small subarachnoid bleed. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The common causes are rupture of a superficially situated AVM, or mycotic aneurysm (associated with acute infective endocarditis). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Occipital lobar hemorrhages, in elderly patients, which extend into the subarachnoid space (intra-extracerebral) have, in a number of instances, been shown to be due to amyloid angiopathy.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Certain primary brain tumours, and some metastatic tumours may also present as an intra -extracerebral lobar hemorrhage.</div> <div> <B><U><IMG SRC="18e40580.jpg" border=0 width="576" height="600" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="18f99f70.jpg" border=0 width="665" height="503" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">brain herniation<IMG SRC="19015f90.jpg" border=0 width="789" height="505" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">brain hemorrhage</U></B></div> <bR> <bR> <div> <B><U>TRAUMATIC LESIONS OF THE CNS</U></B> </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Traumatic injury to the CNS system is common and is especially frequent in young males. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">With cerebrovascular disease it is an area of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >neuropathology</FONT> with high costs to society. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The following discussion is confined to <B>closed head injury</B> and does not include the pathology of penetrating injuries, eg. stab or gun shot wounds, </div> <div> The effects of trauma to the skull and brain, during closed head injury depend upon a number of factors: </div> <div> (a) the shape of the objects causing the trauma,</div> <div> (b) the force of the impact,</div> <div> (c) whether the head is in motion at the time of impact.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Thus the <B>mechanisms</B> of closed head injury are either due to <I><B>contact</B></I> phenomena (usually resulting in focal lesions) or <I><B>acceleration/deceleration</B></I> phenomena (principally causing diffuse axonal injury (DAI).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It is important to realize that severe brain damage can occur in the absence of easily visible external injury and vice versa, and that focal and diffuse lesions may occur in isolation or be combined.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> From a practical and clinical viewpoint there are basically 2 stages in the development of traumatic brain damage: </div> <div> <B>(1) Immediate damage</B> - initiated at the moment of impact. Depending on the type of damage caused, the patient may show immediate signs and symptoms, eg. coma, or the clinical presentation may be delayed for some time (moments to days). </div> <div> <B>(2) Secondary events</B> - these are potentially preventable or reversible and include brain swelling, hypoxia, infection and secondary haemorrhage - all resulting in raised intracranial pressure and its complications</div> <DIV ALIGN="LEFT"></DIV> <div> <B>CONTACT PHENOMENA &/OR ACC/DEC INJURY</B></div> <div> <B>(Mechanism of injury) </B></div> <bR> <div> <B>PRIMARY DAMAGE</B></div> <div> <B> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="471" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 16 WIDTH="232"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="232" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="232"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="232" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></B></div> <bR> <div> <B> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="627" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="316"><div> <B>FOCAL</B></div> </tD> <tD VALIGN=CENTER WIDTH="304"><div> <B>DIFFUSE</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 16 WIDTH="316"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="316" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="304"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="304" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="316"><div> <B>SKULL FRACTURES</B></div> </tD> <tD VALIGN=CENTER WIDTH="304"><div> <B>DIFFUSE AXONAL INJURY</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 ><NOBR><div> <B>CONTUSIONS/LACERATIONS</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="304"><div> <B>(DAI)</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="316"><div> <B>HAEMORRHAGES</B></div> </tD> <tD VALIGN=CENTER WIDTH="304"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="304" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></B></div> <bR> <div> <B>SECONDARY EVENTS</B></div> <div> <B> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="472" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 16 WIDTH="174"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="174" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="289"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="289" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></B></div> <bR> <div> <B> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="628" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="229"><div> <B>FOCAL</B></div> </tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="390"><div> <B>DIFFUSE</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 16 WIDTH="229"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="229" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="390"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="390" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 57 ><NOBR><div> <B>SECONDARY HAEMATOMAS</B></div> <div> <B>INFECTIONS (abscess)</B></div> <div> <B>INFARCTION (spasm)</B></div> </NOBR></tD> <tD VALIGN=CENTER><NOBR><div> <B>PERFUSSION SWELLING</B></div> <div> <B>& CEREBRAL OEDEMA</B></div> </NOBR></tD> <tD VALIGN=CENTER><NOBR><div> <B>DIFFUSE HYPOXIC</B></div> <div> <B>DAMAGE</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 16 WIDTH="229"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="229" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="217"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="217" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="172"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="172" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></B></div> <bR> <div> <B> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="507" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="497"><div> <B>RAISED INTRACRANIAL PRESSURE</B></div> </tD> </tR> </TABLE></B></div> <bR> <div> <B>HERNIAS</B></div> <bR> <div> <B>DEATH</B></div> <bR> <div> <B>Diffuse axonal injury</B>,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> in its mildest form is probably responsible for concussion, but if severe is associated with prolonged unconsciousness from the moment of injury. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The mechanism is one of widespread tearing of axons due to shearing forces during acceleration/deceleration of brain. While focal injuries such as contusions, lacerations and intracranial haematomas (see below), are usually readily apparent radiologically, DAI is more subtle. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">However, although the torn axons are in themselves radiographically invisible, concomitant tearing of small blood vessels within the brain results in small haemorrhages which may be radiologically detectable, and typically involve the corpus callosum and dorsolateral quadrant of the rostral brainstem. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The callosal haemorrhages may be associated with bleeding into the ventricular system, which will also be visible on the CT scan. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">NB: Cerebral oedema itself, is not a complication of pure DAI. However, trauma related perfusion swelling does occur in younger patients, sometimes following relatively minor trauma or with severe injury in association with DAI. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The reasons for such swelling are as yet uncertain but are possibly associated with the presence of an immature autoregulatory mechanism. </div> <bR> <bR> <div> <B><U>TRAUMATIC INTRACRANIAL HAEMATOMAS</U></B><B><U> </U></B></div> <div> While the surgeon is unable to influence parenchymal damage occurring in DAI, intracranial haematomas are of particular importance as they are potentially treatable and curable. CT scanning of trauma patients has shown that intracranial haematomas may be present before they produce clinical deterioration. </div> <bR> <bR> <div> <B>A. Dural associated hematomas</B> </div> <bR> <bR> <div> 1. <I><B>Epidural (extradural) hematomas</B></I> are usually associated with skull fractures with tearing of one of the meningeal arteries. </div> <div> Because they result from arterial bleeding they cause a rapid rise in intracranial pressure and thus represent a medical emergency, requiring surgical drainage. </div> <bR> <div> 2. <I><B>Subdural hematomas</B></I><I> </I></div> <div> <I><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">(SDH)</I> by contrast occur after rupture of bridging veins and are often associated with blunt trauma without skull fractures. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They occur most frequently over the convexities, covering the entire hemisphere and are manifested clinically by fluctuating levels of consciousness. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They are initially composed of clotted blood which appears hyperdense on CT scan, and there may be associated isodense perfusion swelling of the underlying hemisphere, which probably lasts for about one week. If the haematoma is left undrained and the patient survives, the blood clot undergoes liquefaction within 5-21 days, becomes encapsulated in a membrane composed of granulation tissue derived from the dura, and is now called a chronic SDH.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In alcoholic or elderly patients with cerebral atrophy, <B>SDH's</B> are often bilateral and may occur after insignificant or even unnoticed trauma. Such undiagnosed bleeds can resolve spontaneously, or may, because of repeated small haemorrhages from immature vessels present in the chronic subdural membrane, cause a slow increase in size, only give rise to symptoms weeks or months after the initial injury. Symptoms are often vague and may be masked by concomitant disease. The CT scan has greatly simplified this diagnostic problem as these chronic SDH's are readily identified by this modality. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It should be remembered that the late (mis)diagnosis of intracranial haematoma is one of the most important factors contributing to mortality and morbidity after head injury. </div> <bR> <bR> <div> <B>B. Intracerebral hematoma, contusions and laceration</B> </div> <div> <I><B>Contusions</B></I> are focal areas of cortical haemorrhagic necrosis occurring at the crest of a gyrus and are said to be the hallmark of closed head injury; they may occur at the site of impact (coup lesions), or at a point opposite (contrecoup lesions). </div> <div> The latter have a characteristic distribution whatever the site of the original injury, affecting particularly the frontal and temporal poles.</div> <div>  (A distinction is made between contusions and lacerations: in the former the pia is intact, but with lacerations the pia-arachnoid and underlying brain tissue are torn). </div> <div> Contusion/laceration of the brain may be accompanied by pure <I><B>intracerebral hematoma</B></I>, often multiple, mainly involving temporal and frontal regions. (Burst lobe is a convenient term to describe the coexistence of SDH, contusions and a hematoma in the underlying white matter).</div> <bR> </td> </tr></table></body>