PATHOLOGY part1

<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="12f96be0.gif" border=0 width="150" height="190" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">  <SCRIPT TYPE="text/javascript" LANGUAGE="javascript"> s="na";c="na";j="na";f=""+escape(document.referrer) </SCRIPT> <SCRIPT TYPE="text/javascript" LANGUAGE="javascript1.2"> s=screen.width;v=navigator.appName if (v != "Netscape") {c=screen.colorDepth} else {c=screen.pixelDepth} j=navigator.javaEnabled() </SCRIPT> <SCRIPT TYPE="text/javascript" LANGUAGE="javascript"> function pr(n) {document.write(n,"\n");} NS2Ch=0 if (navigator.appName == "Netscape" && navigator.appVersion.charAt(0) == "2") {NS2Ch=1} if (NS2Ch == 0) { 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NERVOUS SYSTEM</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <bR> <bR> <bR> <div> <B><U>SUPPURATIVE INFECTIONS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B><U>SUBDURAL EMPYEMA</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B><U>SUPPURATIVE MENINGITIS</U></B></div> <div> <B><U>BRAIN ABSCESS</U></B></div> <div> <B><U>MYCOBACTERIAL INFECTIONS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B><U>TREPONEMAL INFECTIONS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B><U>FUNGAL INFECTIONS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B><U>CRYPTOCOCCOSIS</U></B></div> <div> <B><U>VIRAL DISEASES</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B><U>HERPES SIMPLEX ENCEPHALITIS</U></B></div> <div> <B><U>CYTOMEGALOVIRUS ENCEPHALITIS</U></B></div> <div> <B><U>HIV INFECTIONS</U></B></div> <div> <B><U>PRION DISEASES</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <bR> <div> <IMG SRC="0b0369b0.gif" border=0 width="566" height="411" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">Diagram of the brain, its coverings and spaces involved by CNS infectionshttp://www.akronchildrens.org/neuropathology/fig5-1.html</div> <bR> <DIV ALIGN="LEFT"></DIV> <div> <B>PATHOLOGY OF SEPTIC MENINGITIS</B></div> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="1049" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="248"><div> SEPTICAEMIA</div> </tD> <tD VALIGN=CENTER COLSPAN=3><NOBR><div> SEPTICAEMIC ENCEPHALOPATHY WITH OVERWHELMING INFECTION/TOXAEMIA</div> <div> <I>(especially with pneumo- & meningococcus)</I></div> </NOBR></tD> <tD VALIGN=TOP WIDTH="124"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="38" ALIGN="bottom" WIDTH="124" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 96 WIDTH="248"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="96" ALIGN="bottom" WIDTH="248" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="372"><div> Endotoxic shock</div> <div> Diffuse neuronal damage</div> <div> Shwartzman reaction</div> <div> Vasculopathy</div> <div> Acute brain swelling</div> <div> Hypoxia</div> </tD> <tD VALIGN=CENTER WIDTH="58"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="96" ALIGN="bottom" WIDTH="58" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="231"><div> E D</div> <div> A E</div> <div> R A</div> <div> L T</div> <div> Y H</div> </tD> <tD VALIGN=TOP WIDTH="124"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="96" ALIGN="bottom" WIDTH="124" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 56 WIDTH="248"><div> after +/- 24 hrours</div> <div> PURULENT EXUDATE</div> <div> in ...</div> </tD> <tD VALIGN=CENTER WIDTH="372"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="56" ALIGN="bottom" WIDTH="372" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="58"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="56" ALIGN="bottom" WIDTH="58" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="231"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="56" ALIGN="bottom" WIDTH="231" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP WIDTH="124"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="56" ALIGN="bottom" WIDTH="124" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 35 WIDTH="248"><div> subarachnoid space </div> </tD> <tD VALIGN=CENTER WIDTH="372"><div> Leptomenigitis </div> <bR> </tD> <tD VALIGN=CENTER><NOBR><div> Vasculitis </div> <bR> </NOBR></tD> <tD VALIGN=CENTER WIDTH="231"><div> Infarcts </div> <bR> </tD> <tD VALIGN=TOP WIDTH="124"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="35" ALIGN="bottom" WIDTH="124" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 56 ><NOBR><div> ventricles </div> <div> <I>(characteristic & early in neonates)</I></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="372"><div> Choroid plexitis</div> <div> Ventriculitis </div> <div> Ependymitis</div> </tD> <tD VALIGN=CENTER><NOBR><div> <I>empyema</I> </div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="231"><div> Acute hydrocephalus</div> </tD> <tD VALIGN=TOP WIDTH="124"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="56" ALIGN="bottom" WIDTH="124" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 16 WIDTH="248"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="248" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="372"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="372" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="58"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="58" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="231"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="231" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP WIDTH="124"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="124" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 54 WIDTH="248"><bR> <div> after +/- 72 hours</div> </tD> <tD VALIGN=CENTER WIDTH="372"><div> Subependymal</div> <div> venous thrombosis </div> <bR> </tD> <tD VALIGN=CENTER><NOBR><div> Periventricular</div> <div> necrosis </div> <bR> </NOBR></tD> <tD VALIGN=CENTER WIDTH="231"><div> Cavaties & cysts</div> <div> in survivors </div> <bR> </tD> <tD VALIGN=TOP WIDTH="124"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="54" ALIGN="bottom" WIDTH="124" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 54 ><NOBR><div> Commencing leptomeningeal</div> <div> fibroblastic proliferation</div> <bR> </NOBR></tD> <tD VALIGN=CENTER WIDTH="372"><div> Blockage of</div> <div> CSF pathways </div> </tD> <tD VALIGN=CENTER><NOBR><div> </CENTER</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="231"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="54" ALIGN="bottom" WIDTH="231" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="124"><div> Obstructive hydrocephalus</div> </tD> </tR> </TABLE></div> <bR> <bR> <div> , the brains </div> <div> of AIDS patients may show various types of <I>HIV-associated pathology</I>, </div> <div> with unknown or disputed pathogenesis: </div> <div> 1. Myelin palor </div> <div> 2. Vacuolar myelopathy </div> <div> 3. Vacuolar leucoencephalopathy </div> <div> 4. Lymphocytic meningitis </div> <div> 5. Diffuse poliodystrophy </div> <div> 6. Spongiform change </div> <div> 7. Cerebral vasculitis </div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">most bacterial infections spread to the brain by the bloodstream.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Bacteria can penetrate into the brain from the environment if there is a break in the continuity of these protective layers.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <B><U>Such a discontinuity may be due to congenital defects (encephalocele, meningomyelocele) or caused by trauma or a shunt.</U></B> </div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Bacteria can also spread to the brain from infected adjacent air sinuses, the middle ear and the mastoids</U></B>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They can reach the brain either directly through the bone, especially in areas where the bone plate is thin, or through veins <B>(diploic veins, dural venous sinuses, intracerebral veins</B>). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The various protective layers may also help contain infections within certain spaces or planes.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <bR> <div> <B><U>Epidural abscess.</U></B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">An epidural space filled with adipose tissue exists normally around the spinal cord. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A spinal epidural abscess arises when organisms from osteomyelitis and tuberculosis of the vertebral column spread to this space.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> There is no epidural space normally in the cranium. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">However, a cranial epidural abscess may develop when bacteria colonize a traumatic epidural hematoma or when infection from air sinuses extends in the plane between the dura and bone.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B> <A NAME="subdural"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B><U>SUBDURAL ABSCESS (SUBDURAL EMPYEMA)</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">Infection may spread to the subdural space from air sinuses or from the middle ear. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The subdural space is traversed by bridging arteries and veins but has no vascular network of its own</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Therefore, antibiotics have no access to this space. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Treatment of the subdural abscess consists of evacuation plus local instillation of antibiotic</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Epidural and subdural abscesses are collections of pus. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If they are large enough, they compress the brain or spinal cord, resulting in loss of function, and increased intracranial pressure.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Locally, neutrophils destroy tissues with their enzymes. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This damage is followed by formation of vaxcula inflammatory tissue and then a fibrous scar. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Histologically, acute subdural empyema shows mainly a layer of neutrophils overlying the arachnoid membrane. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The inflammatory cells may infiltrate the arachnoid membrane and extend into the subarachnoid space.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <bR> <div> <B><U>INFECTIVE DISORDERS</U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Meningitis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Encephalitis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Other infective conditions</div> <bR> <div> <B><U>Acute Pyogenic Leptomeningitis: </U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">An acute inflammation of the leptomeninges and subarachnoid space; usually the infection is diffuse, since the CSF is a good culture medium & rapidly disseminates bacteria throughout the subarachnoid space. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The most common organism in neonates is E. Coli; in infants & children, H. old, S. Pneumoniae. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The most common routes of infection are hematogenous or direct extension from infection of an adjacent structure (mastoiditis, otitis media, sinusitis). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The CSF is cloudy and contains many neutrophils; protein is increased and glucose is reduced; </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Gram stain may demonstrate the causative organism (Gram negative diplococci = meningococci). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The meninges are opaque due to a covering of exudate , which often extends along the arachnoidal vessels </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This exudate tends to concentrate over the cerebral hemispheres in S. Pneumoniae meningitis; it tends to be basal in location in H. Influenzae infection. Neutrophils are present in the subarachnoid/Virchow - Robin spaces  and sometimes fill these spaces. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Secondary invasion of the brain produces a meningoencephalitis. In fulminant cases, there may be involvement of the leptomeningeal veins - which may develop a septic thrombophlebitis with secondary venous infarction of the brain.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Organization of the subarachnoid exudate can produce adhesions (adhesive arachnoiditis) - obstructing the flow of CSF and producing a communicating hydrocephalus</div> <bR> <bR> <div> <B><U>1. Meningitis</U></B></div> <div> Meningitis refers to an inflammatory process in the CSF/leptomeninges. It may be classified as follows:</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">acute pyogenic (bacterial) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">aseptic (viral) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">chronic (bacterial or fungal)</div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Chronic meningitis occurs when low-grade infections affect the meninges.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Often these are basal and cause thickening and fibrosis of the leptomeninges. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Involvement of cranial nerves and vessels in the inflammatory/fibrotic process may result in cranial nerve palsies or infarcts, or the fibrosis may result in hydrocephalus</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Suppurative meningitis is the infection of the arachnoid membrane, subarachnoid space, and cerebrospinal fluid by bacteria. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The subarachnoid space is bounded externally by the arachnoid membrane and internally by the pia and dips into the brain along blood vessels in the perivascular ( Virchow-Robin) spaces.</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" >It extends from the optic chiasm to the cauda equina and surrounds the brain and spinal cord completely.</FONT> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Meningitis may have a focal origin (sinusitis, mastoiditis, brain abscess, penetrating injury, congenital defect), but more commonly results from hematogenous dissemination. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The most common organisms of bacterial meningitis in children and adults are </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">streptococcus pneumoniae </B>and<B> Neisseria meningitidis.</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <B>Hemophilus influenzae</B>,<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT>is very infrequent now in young children thanks to vaccination.</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </B>In newborns, the most common organisms are <B>Eschericia coli and beta hemolytic streptococcus group B.</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Babies are frequently infected during passage through the birth canal. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These organisms colonize the nasopharynx. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">From there, they get into the blood stream and are spilled into the CSF through the leaky capillaries of the choroid plexus.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The CSF is an ideal medium for the spread of bacteria because it provides enough nutrients for their multiplication and has no phagocytic cells, immunoglobulins or complement.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Initially, bacteria multiply uninhibited and can be identified in smears,<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT>cultures, or by ELISA detection of their antigens before there is any inflammation. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When bacteria die, lipids and oligosaccharides, including endotoxin, are released from their walls.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Some of these components cause vascular injury and shock.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Symptoms of sepsis may develop and even death from gram-negative shock may occur before any inflammation appears. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Bacterial cell wall components also induce monocytes, astrocytes and microglial cells to produce interleukin-1 (IL-1) and tumor necrosis factor. These cytokines attract circulating neutrophils and monocytes into the CSF</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A spinal tap at this point shows hundreds of neutrophils, elevated protein (from dying neutrophils) and low glucose (because it is consumed by the bacteria and inflammatory cells). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The CSF may change into pus.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This purulent exudate covers the convexities of the brain and settles along the base of the brain, around cranial nerves and the openings of the fourth ventricle</div> <bR> <div> <IMG SRC="0b2f44f0.gif" border=0 width="500" height="335" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="0b4f42c0.gif" border=0 width="500" height="300" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="Arial" >Bacterial meningitis. Purulent exudate along the base of the brain</FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In addition to fever and other symptoms of generalized infection, the patient with meningitis has<B> severe headache</B> and a<B> stiff neck</B>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The inflamed spinal structures are sensitive to stretch, and pain can be elicited by maneuvers that stretch the spine, such as bending the leg with an outstretched knee or bending the neck. As the disease progresses, confusion, coma and seizures develop. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These complications are due to<B> increased intracranial pressure </B>and to a <B>toxic metabolic encephalopathy</B>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The latter is probably due to unknown diffusible substances (perhaps cytokines) that have a neurotoxic action.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Increased intracranial pressure is due to cerebral edema and increased CSF volume. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Vascular damage induced by IL-1 and TNF allows fluid to leak into the interstitial space and proteins to leak into the CSF.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Polyunsaturated fatty acids released by dying neutrophils can also increase vascular permeability. Neutrophils invade cranial and spinal roots and blood vessels in the subarachnoid space. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lysosomal enzymes released by dying neutrophils eat away at these tissues, causing severe chemical injury. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Vasculitis</B> induces thrombosis</div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Thus, meningitis can cause<B> cranial nerve deficits</B> and<B> ischemic infarction</B> of brain. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In addition, the thick fibrinopurulent exudate in the subarachnoid space organizes into fibrous tissue that blocks the exits of the fourth ventricle and hinders CSF circulation. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This causes<B> hydrocephalus</B></div> <div> <IMG SRC="0b6e87f0.gif" border=0 width="488" height="383" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="System" >Hydrocephalus secondary to meningitis.</FONT><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">These complications take time to develop and may appear after the inflammation has subsided.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They may be prevented by prompt treatment.<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 glia limitans, a thick tight mesh of astrocytic processes, joined by dense junctions and covered by basement membrane, is impenetrable to bacteria and neutrophils.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Undamaged, it provides an effective barrier that prevents meningitis from spreading into brain tissue. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Thus, brain abscess as a complication of meningitis is rare.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Brain dysfunction and injury are caused more often by increased intracranial pressure, <B>HIE</B> due to shock, and from<B> ischemic infarcts</B> due to vasculitis.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Brain damage from these complications may be devastating or fatal, especially in newborn babies in whom the brain can literally melt away.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG SRC="0b8f4710.gif" border=0 width="500" height="369" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="Arial" >. Severe destruction of the brain in a baby with Group B Streptococcal meningitis</FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Brain damage in meningitis is, for the most part, due to host responses that cause inflammation.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These responses have a protective purpose (to eliminate bacteria) but are excessive and indiscriminate.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They damage everything in their way, mostly host tissues. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Modulating these reactions (in addition to killing bacteria) can reduce the complications of meningitis</div> <bR> <bR> <div> <B><U>2. Abscess</U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cerebral abscesses were traditionally associated with a high mortality but this has improved significantly with current treatment regimens. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800000000.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">the brain abscesses act as a tumor in the brain with the same symptomatology as location and headache the only difference will be the fever associated with.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Brain abscess is a newly formed cavity within the brain filled with pus. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Infection spreads from adjacent air sinuses or the middle ear, or via the blood stream from the lungs (bronchiectasis, lung abscess), or from the heart (bacterial endocarditis). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The location of the abscess corresponds to its source.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Frontal sinusitis causes frontal lobe abscess<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT>and mastoiditis causes temporal lobe abscess.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Hematogenous abscesses are often multiple. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The bacterial flora of brain abscess depends on the source of the infection.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In the case of sinusitis and otitis, it is usually mixed, including anaerobes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Bacteremia alone does not cause brain abscess. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Some tissue damage, probably a small ischemic lesion, is required to start the process. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Bacteria spreading around this necrotic nidus cause brain necrosis and acute inflammation<B> (cerebritis)</B>. </div> <div> <IMG SRC="0ba19b50.gif" border=0 width="281" height="437" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">Cerebritis. Brain necrosis, acute inflammation and bacteria. This will evolve into an abscess</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The necrotic center cavitates, while at the periphery, a vascular zone of brain tissue with macrophages, mononuclear cells and reactive astrocytes contains the infection. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In 4-5 weeks, collagen (derived from vascular cells) laid down in this reactive zone forms a thick<B> capsule</B> that walls off the infection.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Increased vascular permeability in the inflamed tissue causes <B>cerebral edema</B>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Vascular leakage accounts also for the<B> </B>"ring enhancing" pattern after contrast injection which gives abscess its characteristic radiological image (necrotic tumors may have a similar appearance). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Systemic antibiotics are effective in the phase of cerebritis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Once a capsule develops, it is a barrier to antibiotics.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Thus, the treatment of chronic abscess needs drainage or surgical excision in addition to local and systemic antibiotics.<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">Brain abscess causes loss of neurological function due to destruction of brain tissue. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">More important, it causes increased intracranial pressure.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Its mass effect is due to the collection of pus and to<B> cerebral edema</B> around the abscess. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Since the infection is contained within brain tissue, the CSF usually shows only a few mononuclear cells with normal protein and glucose.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B><U>3. Encephalitis</U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Primary infection of the brain is not common. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Viral diseases are the usual cause, but bacteria (eg syphilis), fungi (eg cryptococcus) and parasites (eg toxoplasmosis in AIDS patients) can also be seen</B>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> A number of different patterns can be seen, depending on the causative agent.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> For example, Herpes simplex typically causes necrosis of neurones with a predilection for the temporal lobes. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Other viruses such as the arthropod-borne viruses (in Australia an example is Murray Valley encephalitis) may be more diffuse, or in some cases there may be striking tropism for one particular cell type.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> An example of this is poliovirus, which affects the motor neurones of the anterior horn in the spinal cord, causing paralysis. In most cases the macroscopic appearance of encephalitis is not diagnostic</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Spongiform encephalopathy is a special form of encephalitis that is quite topical because of mad cow disease in the United Kingdom.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Spongiform encephalopathy in humans was characterised in cannibals from the Niuginian highlands, who showed rapidly developing dementia and sponge-like vacuoles in the grey matter of their brains.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It was called kuru and was found to be due to the consumption of human brains. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Subsequntly, it was recognised that this was a similar disease to another one in humans (Creutzfeldt-Jakob disease), sheep (scrapie), and cows (bovine spongiform encephalopathy -BSE- or mad cow disease).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> A rare inherited form also occurs in humans.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The unusual nature of the agent was recognised early.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Although initially thought to be due to a "slow virus", the agent had characteristics of a protein; thus <U>pro</U>teinaceous <U>in</U>fective agent or <B>prion. </B>It appears that the prion protein is an abnormally folded form of a native cerebral cellular protein, and causes disease by gradually altering the conformation of the native protein so it forms sheets</div> <bR> <div> <B>note that the encephalitis can be infectious or not infectious.</B></div> <bR> <div> <B><U>Pathologic Characteristics of Viral Encephalitis</U></B><B> </B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Parenchymal and perivascular mononuclear cell infiltrates(lymphocytes, plasma cells, and macrophages) & mononuclear cells in the CSF. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Microglial nodules  which form around degenerate/necrotic neurons (Neuronophagia). Also, many microglia have elongated nuclei(rod cells). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Inclusion Bodies: These are specific "markers" for viral infection </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Nuclear Inclusions (Cowdry Type A): H. simplex, Varicella-Zoster, Cytomegalovirus , Subacute Sclerosing Panencephalitis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cytoplasmic Inclusions: Negri body (rabies) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Tropism - many viruses primarily infect specific subpopulations of cells; </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Herpes Zoster - dorsal root ganglion cells</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Poliomyelitis virus - anterior horn motor neurons</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Papovavirus - <FONT SIZE="3" COLOR="#800000" FACE="Arial" >oligodendroglia</FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Rabies virus - pyramidal neurons of the hippocampus & Purkinje cells</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Herpes Simplex - inferior frontal and temporal lobes</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cytomegalovirus - ependymal cells and microglia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Latency- Herpes Simplex and Varicella-Zoster remain latent in host neurons, only to be reactivated months or years after the initial infection. </div> <div> <B><U>Subacute Sclerosing Panencephalitis (SSPE) </U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Occurs in children or young adults, and is always preceeded by a history of measles, or, rarely, measles vaccination or other viral infection (e.g. mumps)- usually in the distant past. It represents a persistent infection by an bodies are found in neurons, <FONT SIZE="3" COLOR="#800000" FACE="Arial" >oligodendroglia</FONT>, and astrocytes; there is a dense fibrillary gliosis(note perivascular mononuclear cells).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Clinically, there are personality changes,involuntary movements, and progressive neurologic deterioration over 2 - 3 years. </div> <div> <B><U>Progressive Multifocal Leukoencephalopathy (PML) </U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A Papovavirus infection of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >oligodendroglia</FONT>l cells. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Because these cells produce myelin, this disease presents with demyelination.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It is associated with immunosuppressed hosts - including advanced hematologic malignancy and AIDS. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> There are multiple poorly demarcated areas of demyelination present within the cerebral, cerebellar, and spinal white matter. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">At the margins of these areas, the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >oligodendroglia</FONT> have enlarged nuclei </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">, which may contain violet/eosinophillic intranuclear inclusions.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Present within the areas of demyelination are bizarre giant astrocytes & foamy macrophages containing myelin break-down products. </div> <div> <B><U>Spongiform Encephalopathies</U></B><B> </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These are a group of diseases caused by transmissible agents called prions (proteinaceous infectious particles) which are not fully characterized.</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Microscopically </B> they all show a characteristic spongiform vacuolation in the gray matter (cortex, basal ganglia, cerebellum, and spinal cord) with neuronal loss and astrocytosis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The spongiform vacuoles are in the processes of neurons and glia.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> There are no inflammatory cells. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Creutzfeld-Jakob Disease - a rare disease, characterized by rapidly progressive dementia and death in 2-3 years. Most cases are sporadic. However, transmission by corneal transplants & contaminated Growth Hormone & autopsy's has been documented and 10-15% of cases are inherited. "New Variant" CJD is thought to be caused by the same agent that produces bovine spongiform encephalopathy (mad cow disease). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Kuru is limited to the Fore tribe of New Guinea, where it is transmitted by cannibalism. It affects primarily the cerebellum, and presents with cerebellar ataxia and a "shivering" tremor. It progresses to complete motor incompacity. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Scrapie is a slow virus disease of goats and sheep. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fatal familial insomnia. </div> <div> <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 COLSPAN=3 BGCOLOR=#FFFFFF HEIGHT= 35 WIDTH="619"><div> <B><U>Opportunistic CNS Infections Associated with AIDS</U></B></div> <bR> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FFFFFF HEIGHT= 20 WIDTH="450"><div> <B><U>Viral Infections:</U></B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF><NOBR><div> Autopsy Incidence</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Subacute (HIV) Encephalitis</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 28%</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> CMV Encephalitis</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 26%</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Nonspecific Encephalitis</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 17%</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Progressive Multifocal</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="168" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Leukoencephalopathy </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 2% </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Varicella-Zoster Encephalitis</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 2%</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Herpes Simplex Encephalitis</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 2%</div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FFFFFF HEIGHT= 20 WIDTH="450"><div> <B><U>Fungal Infections:</U></B></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="168" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Aspergillus </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 1% </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Candida</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 1%</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Cryptococcus</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 3%</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Histoplasmosis</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 1% </div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FFFFFF HEIGHT= 20 WIDTH="450"><div> <B><U>Parasitic:</U></B></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="168" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Toxoplasmosis</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 10% </div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FFFFFF HEIGHT= 20 WIDTH="450"><div> <B><U>Neoplasms:</U></B></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="168" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Primary CNS Lymphoma</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 6% </div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FFFFFF HEIGHT= 20 WIDTH="450"><div> <B><U>Other:</U></B></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="168" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="288"><div> Vacuolar Myelopathy</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="168"><div> 30%</div> </tD> </tR> </TABLE></div> <bR> <div> <B><U><IMG SRC="18101360.jpg" border=0 width="513" height="310" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">proof of viral infection [inclusion bodies]<IMG SRC="1837e3d0.jpg" border=0 width="382" height="317" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">microglial nodules<IMG SRC="185fa3d0.jpg" border=0 width="506" height="317" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">cytomegalovirus</U></B></div> <bR> <div> <B><U>4. Parasitic infections</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hydatid disease </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cysticercosis</div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800000000.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">malaria</div> <bR> <bR> <div> <B><U>MYCOBACTERIAL INFECTIONS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mycobacterial infections, always prevalent in developing countries, are now reappearing in the United States and Europe, especially in immunodeficient persons.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">During hematogenous dissemination of tuberculosis, small caseating lesions (tubercles) develop in the meninges and in brain tissue. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mycobacteria can survive in these lesions for a long time. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When tubercles rupture, mycobacteria are discharged into the CSF causing tuberculous meningitis</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This may happen in the<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT>course of disseminated miliary tuberculosis, or sometimes years later.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The focus of initial infection in the lungs may be undetected. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In some cases, tuberculous meningitis has a fulminant presentation, like bacterial meningitis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In other cases, it presents insidiously and progresses slowly over weeks or months, causing <B>headache, confusion and cranial nerve deficits.</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Infection of the CSF causes initially acute inflammation similar to bacterial meningitis.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Mycobacteria are not eliminated because they have components in their cell walls that enable them to survive in macrophages. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Thus, the organisms are not eliminated. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Two to three weeks after the onset of the infection, sooner in sensitized hosts, a cell-mediated immune reaction develops. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This enhances intracellular killing of mycobacteria by macrophages and eventually leads to necrosis of infected tissue. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Necrotic tissue is yellowish and has a cheesy consistency, hence <B>caseous</B> (L. <I>caseus</I>. cheese)<B> necrosis</B>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The histological findings in tuberculous meningitis are the same as those of mycobacterial infections elsewhere, namely<B> epithelioid cell granulomas</B> with<B> Langhans giant cells</B> and<B> lymphocytic infiltrates.</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">Epithelioid cells are macrophages engaged in mycobacterial killing. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They aggregate in clusters (granulomas) or fuse forming giant cells. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These changes involve the arachnoid membrane and subarachnoid space diffusely. Acid fast organisms can be demonstrated in the granulomas. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mycobacteria produce no exotoxins. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The inflammatory reaction gradually kills the organisms. However, the destructive force of inflammation causes severe damage to vessels, nerves, and the arachnoid membrane with complications (vasculitis, cerebral infarction, hydrocephalus, nerve damage) even more serious than those of suppurative meningitis.<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">Also, unlike suppurative meningitis in which the exudate is usually confined to the subarachnoid space, epithelioid cell granulomas destroy the pia and the surface of the brain. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The CSF in tuberculous meningitis shows pleocytosis with a predominance of mononuclear cells, high protein and low glucose.<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">Tuberculous infection of the brain sometimes results in formation of a mass <B>(tuberculoma)</B> that consists of caseous necrotic material surrounded by epithelioid cell granulomas and mononuclear cells.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <IMG SRC="0bcc76b0.gif" border=0 width="455" height="363" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="System" >Tuberculoma.</FONT><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">Rupture of the tuberculoma and release of mycobacteria into the subarachnoid space cause meningitis.<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">Tuberculosis characteristically produces a chronic basilar meningitis </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The subarachnoid space is distended with an exuberant fibrous exudate, which collects at the base of the brain and extends into the lateral sulci.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Microscopically, there is an exudate composed of plasma cells, lymphocytes, macrophages, and necrotizing granulomas: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Ziehl-Nielson stains reveal acid fast bacilli: <IMG SRC="187f63a0.jpg" border=0 width="502" height="314" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Organization is the rule, and a resultant adhesive arachnoiditis often produces a communicating hydrocephalus</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. Subarachnoid vessels develop an obliterative arteritis - with secondary cerebral/spinal infarction. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There may be secondary entrapment of cranial nerves passing through the affected subarachnoid space. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Uncommonly, a "tuberculoma" forms within the brain  and produces symptoms of a space-occupying lesion similiar to a brain tumor.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The CSF contains increased numbers of mononuclear cells, high protein, and slightly decreased glucose</div> <div> <IMG SRC="189fa350.jpg" border=0 width="506" height="309" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">tuberculoma</div> <bR> <bR> <div> <B><U>TREPONEMAL INFECTIONS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><U> </U></FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Tertiary syphilis produces protean neurological manifestations caused by meningovascular and parenchymal lesions. </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The<B> meningovascular</B> lesions are a lymphoplasmacytic meningitis and intimal thickening of small and medium-size leptomeningeal and parenchymal arteries (endarteritis obliterans- Heubner arteritis).</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The parenchymal lesions are<B> tabes dorsalis</B> (rot of the spinal cord), characterized by inflammation and degeneration of dorsal roots and posterior columns, and<B> general paresis of the insane (dementia paralytica</B>), an encephalitis due to invasion of the brain by spirochetes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In addition, syphilis can cause<B> gummas</B> in the brain. A gumma (L <I>gummi</I> gum) is a rubberry necrotic-inflammatory mass containing spirochetes, that acts like a space-occupying lesion. Syphilis can also cause an acute meningitis during its secondary stage.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lyme disease</B> is caused by the tick-borne spirochete Borrelia burgdorferi. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In its second and third stages, it can cause meningitis, radiculitis, neuropathy and encephalitis leading to ataxia, paralysis, dementia and other neurological manifestations.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The CSF shows mononuclear pleocytosis and mild protein elevation.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The pathology is not well studied. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Presumably, there are lymphoplasmacytic infiltrates and vasculitis in the meninges and brain, similar to changes that have been observed in other tissues.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><U> <A NAME="fungal"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>FUNGAL INFECTIONS OF THE NERVOUS SYSTEM</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 CNS mycoses are, in order of frequency, Candidiasis, Aspergillosis and Cryptococcosis.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They are seen mainly in patients with AIDS and other immunosuppressed states.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Candida and Aspergillus are usually nosocomial infections and involve the brain in the course of generalized infection. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Candida</B> consists of budding yeasts and hyphae.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It causes meningitis, multiple microabsesses or extensive brain necrosis.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG SRC="0bef4380.gif" border=0 width="500" height="312" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="Arial" >. Extensive brain necrosis in Candida meningoencephalitis</FONT></div> <bR> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Aspergillus </U></B><U>and the related soil fungus </U><B><U>Mucor (Rhizopus)</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> are branching hyphae. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They have the tendency to invade blood vessels<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT>and cause thrombosis with cerebral infarction or vascular rupture with cerebral hemorrhage. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mucor is especially common in patients with diabetic ketoacidosis.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It infects the nasal mucosa from where is spreads to the brain.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B> <A NAME="crypto"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B></div> <div> <U>MUCOR</U> may infect the sinuses of diabetic patients with ketoacidosis - with direct invasion of the orbits and CNS - producing rhinocerebral mucormycosis (note broad non-septate hyphae). </div> <div> Mucor has a propensity for vascular invasion with secondary thrombosis and hemorrhagic cerebral infarction. </div> <bR> <bR> <div> <B><U>Cryptococcus</U></B><B><U>,</U></B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">which is a worldwide fungus, present in bird droppings, vegetables and soil, speads to the brain from the lungs and often causes meningitis without involving other organs.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Unlike Candida and Aspergillus, it is most often community acquired. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It may affect healthy individuals, but is particularly common in immunodeficient patients.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Cryptococcus is a 6-7 microns round or oval yeast surrounded by a thick gelatinous capsule</div> <bR> <div> <IMG SRC="0c7f4740.gif" border=0 width="500" height="372" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="System" >Cryptococci in mucinous material.</FONT><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">It grows extensively in the subarachnoid space and perivascular spaces which become cystically distended to the point that brain sections look like Swiss cheese</div> <bR> <div> <IMG SRC="0c9a7790.gif" border=0 width="423" height="377" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="Arial" >Cryptococcus meningitis. Massive numbers of organisms cause distention of perivascular spaces which imparts a Swiss cheese appearance to the brain</FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In immunosuppressed individuals, inflammation is absent or mild. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In immunocompetent hosts, cryptococcus elicits a cell-mediated immune reaction with lymphocytes and epithelioid cell granulomas. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cryptococcus meningitis has an insidious onset and may last from weeks to years. I</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">t can cause hydrocephalus, dementia and focal neurologic deficits.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The CSF in cryptococcosis shows mononuclear pleocytosis, elevated protein and low glucose, similar to tuberculous meningitis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Yeasts can be identified by microscopy of the CSF and their antigens can be detected by latex agglutination.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U>CRYPTOCOCCUS NEOFORMANS</U> often produces a chronic basilar meningitis  Mononuclear inflammatory cells, foreign body giant cells, and the characteristic yeasts  (mucicarmine- positive) are present within the subarachnoid and Virchow - Robin spaces, and produce the characteristic "soap bubble" appearance . India Ink stains of the CSF often demonstrate the encapsulated yeasts, but this test is not performed on tissue sections. </div> <bR> <div> <B> <A NAME="viral"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B><U>VIRAL DISEASES OF THE NERVOUS SYSTEM</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><U> [see also above]</U></FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Viruses enter the body via </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">the respiratory tract (mumps, measles),</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> gastrointestinal tract (enteroviruses), </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">by inoculation from insect bites (arthropod-borne viruses) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and from animal bites (rabies). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most viruses reach the CNS via the bloodstream.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Some viruses including herpes simplex virus(HSV), varicella-zoster virus (VZV), and rabies may also travel to the CNS along nerves.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Viruses are obligate intracellular organisms.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They use cellular machinery for their replication and kill or damage the cells that they infect. Additional brain damage is caused by the cell-mediated immune reaction that they elicit. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The cascade of events that begins with activation of T-lymphocytes by viruses includes the release of potent cytokines (INF-gamma, IL-2, TNF, lymphotoxin) and mobilization of macrophages that not only attack the viruses but assault the host causing severe vascular and tissue injury.<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">Viral infection of the arachnoid membrane and CSF causes headache, stiff neck and mononuclear CSF pleocytosis with normal protein and glucose. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This syndrome is called<B> aseptic meningitis</B>, because no bacterial organisms are isolated. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The most common agents causing aseptic meningitis are enteroviruses.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Involvement of neurons and glial cells by viruses (viral<B> encephalitis</B>) impairs neurological function and causes </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">seizures,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> focal neurologic deficits and </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">coma.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Encephalitis is usually accompanied by viral meningitis whereas aseptic meningitis may occur alone. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The brain is usually involved in the course of generalized viral infection.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In babies (and with some viruses in adults also) there is often severe involvement of other organs. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In many cases, however, damage of other organs is mild or absent. Some viruses have a predilection for certain groups of neurons.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> For instance, poliomyelitis attacks anterior horn cells and varicella-zoster involves sensory ganglion cells. Most viruses have no such special tropism.<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">Histologically, viral infections show inflammation and brain damage. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">At an early phase, inflammation includes neutrophils but later it consists primarily of<B> lymphocytes</B> and macrophages.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These cells infiltrate the arachnoid membrane and brain tissue diffusely but are more concentrated around blood vessels</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Activation of microglia (indigenous macrophages of the brain, like histiocytes of other tissues) causes these cells to proliferate diffusely or to form small clusters,<B> microglial nodules[SEE PICTURE ABOVE]</B></div> <div> which are a histological clue of viral infection.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Tissue damage ranges from individual cell to diffuse brain necrosis involving large contiguous areas. Certain viruses cause<B>intranuclear andcytoplasmic inclusions</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These are eosinophilic masses consisting of packed viral particles and products of their replication</div> <div> <B><IMG SRC="0cbf41c0.gif" border=0 width="500" height="284" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" >HSV encephalitis. Viral particles in intranuclear inclusions</FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Viruses that cause inclusions are </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">herpes simplex</B>,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <B>cytomegalovirus</B>,</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> varicella-zoster</B>,</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> papovaviruses </B>and</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> measles</B>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> When the inflammatory and immune reactions of viral encephalitis subside, the lesions heal with glial scar formation.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> However, lost neurons do not regenerate. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">So, in the aftermath of viral infections, patients are often left with severe permanent neurological deficits (seizures, dementia, paralysis).<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><U> <A NAME="hsv"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>HERPES SIMPLEX ENCEPHALITIS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><U> </U></FONT></div> <bR> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Adult and pediatric (post-neonatal) HSV encephaliti</U></B><U>s </U></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">is caused by HSV type I. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It is the most common year-round viral encephalitis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most people become primarily infected with HSV in their teens or twenties. HSV type I is transmitted by the saliva.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The initial infection causes a stomatitis.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Following this, the virus remains latent in the trigeminal ganglion.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> From this location, reactivated virus can spread either to the skin, along the branches of the trigeminal nerve causing sores on the lips (herpes labialis), or to the brain, infecting the meninges of the anterior and middle cranial fossae.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> From the meninges, the virus extends to the adjacent brain where it affects the <B>temporal and inferior frontal lobes</B> first and more severely and then spreads to the rest of the brain. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Adult HSV encephalitis is limited to the brain.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Its symptoms are fever, confusion, coma and seizures.</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In addition, because of the involvement of the frontal and temporal lobes, patients often display bizarre behaviour, personality changes, anosmia and gustatory hallucinations. </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Survivors may have <B>Korsakoff amnesia, dementia</B> and seizures.<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">Grossly, the brain in advanced HSV encephalitis shows diffuse softening and edema, accentuated by <B>hemorrhagic necrosis of the inferior frontal and temporal lobes.</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <IMG SRC="0cd123b0.gif" border=0 width="530" height="315" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Microscopical exam in the acute phase shows meningeal and perivascular mononuclear cells,<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG SRC="0cff4390.gif" border=0 width="500" height="313" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="Arial" >Adult HSV encephalitis. Perivascular mononuclear cells and diffuse macrophages</FONT></div> <bR> <div> increased microglia and intranuclear<B> inclusion</B>s.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Without treatment, extensive necrosis, macrophage reaction and neovascularization develop. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The end-stage is brain atrophy and gliosis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The degree of brain destruction (especially in the frontal and temporal lobes) and the inflammatory and reactive changes are more severe than any other viral encephalitis and can be detected by imaging.<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">The CSF shows pleocytosis (early neutrophils, late lymphocytes) and elevated protein, depending on the degree of brain necrosis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Glucose is normal. HSV is hard to isolate from CSF. In the past, the diagnosis of HSV encephalitis required brain biopsy with fluorescent antibody staining using anti-HSV antibodies, microscopic study (to detect inclusions and viral particles) and viral culture. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Now, HSV can be detected in CSF by polymerase chain reaction (<B>PCR</B>). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When a patient presents with fever, obtundation, seizures and abnormal CSF, it is preferable to treat with antiviral agents (and antibiotics) rather than defer treatment until the diagnosis is established. In some cases, this approach will result in unnecessary use of antiviral agents.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> However, in patients with HSV encephalitis, prompt treatment will save lives and prevent permanent neurologic deficits.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B>Neonatal HSV infection</B>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Babies contract HSV type II (herpes genitalis) during passage through the birth canal and occasionally transplacentally.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Less frequently, congenital HSV infection is due to HSV type I. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Many babies acquire the infection after birth, in the newborn nursery or at home. Neonatal herpes is often a generalized infection involving most severely the brain, liver and adrenal glands.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It causes a diffuse necrotizing encephalitis, without predilection for the frontal and temporal lobes</div> <bR> <bR> <bR> <div> <B>CYTOMEGALOVIRUS ENCEPHALITIS</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">Cytomegelovirus (CMV) encephalitis in adults is rare and usually occurs as part of a generalized CMV infection in <B>immunocompromised</B> patients. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Infected neurons and glial cells enlarge and develop cytoplasmic and intranuclear inclusions</div> <div> <IMG SRC="0d1d8960.gif" border=0 width="472" height="406" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="System" >CMV encephalitis. Intranuclear and cytoplasmic inclusions and enlargement of infected neurons and glial cells.</FONT><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">Microglial nodules, lymphocytes, and macrophages infiltrate the lesions. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Heavily infected areas become necrotic.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The lesions have a predilection for the walls of the ventricles.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> A pregnant mother who carries CMV may transmit the virus to the fetus across the placenta, causing a generalized<B> fetal CMV infection. </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This infection may develop at any stage during pregnancy and may continue after delivery. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Infants with congenital CMV infection have variable involvement of the brain and other organs. Prenatal CMV infection often causes necrosis of brain tissue, especially of the walls of the lateral ventricles.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG SRC="0d3f42d0.gif" border=0 width="500" height="301" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="Arial" >Prenatal CMV encephalitis. Periventricular necrosis and calcification</FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Necrotic areas<B> calcify</B> and can be detected by imaging.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Infection before mid-gestation may derange the process of neuronal migration, causing<B> microcephaly and cortical dysplasia.</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B>HIV INFECTIONS</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > [see table above]</FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Human immunodeficiency virus (HIV)</B>infects and destroys selectively T4 lymphocytes, causing immune deficiency. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Consequently, AIDS patients are susceptible to opportunistic infections.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The most common of these are CNS toxoplasmosis, cryptococcosis and other mycoses, CMV encephalitis and papovavirus infections. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Historically, opportunistic infections attracted attention to AIDS long before it became known that HIV can also directly involve the brain. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">AIDS patients develop cerebral or other extranodal B-cell lymphomas due to loss of the surveillance function of T-cells. HIV also infects the nervous system directly, causing aseptic meningitis, encephalitis, leukoencephalopathy, myelopathy, neuropathy and myopathy. </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The most common of these direct effects, HIV encephalitis (AIDS-dementia complex), causes progressive memory loss, intellectual deterioration, behavioral changes, and motor deficits. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HIV has been detected in the brains of patients with HIV encephalopathy by DNA analysis and HIV-specific immunoglobulin is produced intrathecally.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Pathologically, HIV encephalopathy is characterized by diffuse myelin damage (spongy myelinopathy, gliosis), neuron loss, vascular damage, microglial nodules, lymphocytic infiltrates and multinucleated giant cells.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG SRC="0d5f4680.gif" border=0 width="500" height="360" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="Arial" >HIV encephalitis. Multinucleated giant cell</FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These giant cells are the hallmark of HIV encephalitis.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The inflammatory reaction in HIV encephalitis is mild compared to other CNS infections and does not fully explain the clinical manifestations.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> HIV can be transmitted from the infected mother to the fetus, resulting in congenital HIV infection.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The lesions of congenital HIV encephalitis are more severe than those of the adult form and may result in microcephaly.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> One additional distinctive feature of congenital AIDS is basal ganglia calcification.<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">Despite intensive investigation, the pathogenesis of HIV encephalitis remains obscure. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The virus is presumably brought into the subarachnoid and perivascular spaces by infected T4 cells and monocytes. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The next step is penetration of HIV into brain parenchyma.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This may be caused by migration of infected cells into brain tissue or phagocytosis of such cells by microglia.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In addition, microglial cells have T4 receptors and can be infected by HIV.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Once the virus enters into brain tissue, it resides in macrophages and microglia which fuse, forming multinucleated giant cells.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Fusion is caused by an action of the HIV envelope glycoprotein and plays a part in killing of infected cells. HIV has been demonstrated by immunohistochemistry in neurons and astrocytes but the significance of this observation is not clear. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There is no evidence of a productive infection of either neurons or glial cells. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Therefore, neuronal and white matter damage is not a direct effect of HIV. It is probably caused by cytokines such as TNF produced by activated microglial cells, viral products and other types of HIV-brain interactions.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> HIV envelope glycoprotein gp 120 activates NMDA receptors and induces a cascade of excitotoxic events. The pathology of HIV myelopathy resembles subacute combined degeneration. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This suggests that metabolic changes induced by HIV may contribute to the damage of myelin.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B> <A NAME="prion"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B></div> <bR> <div> <B>PRION DISEASES (TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES)</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Prions</U></B> (pronounced pree-ons, an acronym for proteinaceous infectious particles) are abnormal isoforms of a neuronal membrane glycoprotein. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The function of the normal protein (PrP<FONT SIZE="1" COLOR="#000000" FACE="Verdana" >C</FONT>) is not known.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Normally it occurs as an alpha-helix. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A change in its folding pattern into a beta sheet (PrP<FONT SIZE="1" COLOR="#000000" FACE="Verdana" >Sc</FONT>) presumably alters its function, resulting in neuron degeneration and loss. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It also makes the protein resistant to the action of proteases and causes </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">it to precipitate as insoluble amyloid. Such a change in conformation from PrP<FONT SIZE="1" COLOR="#000000" FACE="Verdana" >C </FONT>to PrP<FONT SIZE="1" COLOR="#000000" FACE="Verdana" >Sc</FONT> may come about as a result of mutations of the PrP<FONT SIZE="1" COLOR="#000000" FACE="Verdana" >C</FONT> gene (on chromosome 20) that alter its amino acid sequence.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Also, when extrinsic abnormal prions are introduced into the body, they interact with normal indigenous prions and, acting as templates, cause normal prions to change their conformation into abnormal. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This conversion apparently takes place on a large scale. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The transmissibility of prion diseases has been proven by animal experiments. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Natural transmission from animal to animal (especially in sheep) has been known for many years.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In a few instances, also, prion diseases have been accidentally transmitted from human to human by transplantation of tissues (lens) or injection of pituitary extracts from patients with prion diseases. In 1996, transmission of bovine spongiform encephalopathy to humans was reported in England.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B><U>The human prion diseases are:</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="788" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 226 WIDTH="778"><div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Creutzfeldt-Jakob disease, </B>sporadic and familial (see below).<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Kuru</B>. A now-extinct disease of New Guinea natives, transmitted by eating the brains of dead persons who had the disease.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Gerstmann-Straussler syndrome</B>. An autosomal dominant form of ataxia.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fatal familial insomnia</B>. An autosomal dominant sleep disorder with pathological lesions in the thalamus.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">New variant of Creutzfeldt-Jakob disease</B>. Cases of CJD reported in the United Kingdom, suspected of being transmitted by consumption of contaminated meat.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> </tR> </TABLE></div> <DIV ALIGN="LEFT"></DIV> <div> <B><U>The most common animal prion diseases are:</U></B></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="727" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 264 WIDTH="717"><div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Scrapie</B>. An important disease of sheep that has been known for over 100 years. The term derives from the fact that sick animals rub against rocks or other hard surfaces, destroying their fleeces. The discovery of transmissibility and other important aspects of the biology of prion diseases was based on knowledge of scrapie. The suffix sc in PrPsc is derived from scrapie.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Bovine spongiform encephalopathy (BSE)</B>-mad cow disease.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Transmissible mink encephalopathy</B>.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Wasting disease of deer and elk</B>.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> Prion diseases have also been reported in several other domesticated and wild animal species and can cross from one species to another. Experimental transmission to primates and guinea pigs has played an important role in elucidating their pathogenesis.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> </tR> </TABLE></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pathology, in prion diseases, develops only in the brain. No other organ is affected.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Early on, neurons develop intracytoplasmic vacuoles. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">As the disease progresses, vacuolization becomes more pronounced and, microscopically, the cortical neuropil develops a spongy appearance, hence the term spongiform encephalopathy. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Advanced cases show neuron loss, gliosis, and brain atrophy.<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">Cerebellar atrophy is usually severe. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Unlike most cerebellar degenerations, there is more pronounced loss of granular neurons than Purkinje cells</div> <div> <IMG SRC="0daf4280.gif" border=0 width="500" height="296" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="System" >Creutzfeldt-Jacob disease. Cerebellar degeneration. Loss of granular neurons with relative preservation of Purkinje cells.</FONT><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">There is no inflammation. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The CSF is normal.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The changes are confined to the gray matter (the primary pathology involves the neuronal body). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In some cases, prion proteins precipitate as<B> amyloid plaques</B>.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <bR> <bR> <div> <B>Creutzfeldt-Jakob disease (CJD)</B> is the most common prion disease of humans. </div> <div> It affects middle aged or old persons and causes </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">dementia, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">myoclonus, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ataxia and </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">other neurological abnormalities. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The EEG shows diffuse slowing or a characteristic periodic burst suppression pattern. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CJD is inexorably progressive and fatal within 1 to 2 years. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A definitive diagnosis can only be made by a brain biopsy or autopsy showing the characteristic spongy change. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Abnormal prions can be detected in brain tissue extracts by ELISA and in tissue sections by immunohistochemistry. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A protein called 14-3-3 has been recently reported to be elevated in the CSF of patients with CJD.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This protein was also found in a few patients with cerebral infarcts, HSV encephalitis and other conditions that can be distinguished clinically from CJD but was not present in pathologically confirmed Alzheimer disease.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Detection of this protein by immunoassay promises to provide a much needed premortem diagnostic test for CJD.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <B><U>to read for your information</U></B></div> <div> <B>Between 1994 and 1997, 22 cases of a </B><B>new variant of CJD</B><B> were reported from England. These cases are suspected of having been caused by consumption of meat products contaminated by BSE. The patients were young people and had prominent psychiatric manifestations and ataxia. The brain showed spongiform encephalopathy and amyloid plaques.</B><FONT SIZE="3" COLOR="#336633" FACE="Arial" ><B> </B></FONT></div> <bR> <bR> <div> <B>CJD affects one in every million people. Ten to fifteen percent of cases are </B><B>familial</B><B>, autosomal dominant. Most familial cases are associated with a mutation at codon 200 of the PrP gene resulting in a Glu to Lys substitution.There are other less common mutations. These mutations presumably cause the PrP protein to misfold spontaneously. Mutations of the PrP gene also cause the Gersmann-Straussler-Scheinker syndrome and fatal familial insomnia.</B><FONT SIZE="3" COLOR="#990000" FACE="Arial" ><B> </B></FONT></div> <div> <B>Over 100 cases of CJD have been caused by injection of growth hormone and gonadotrophin extracted from cadaveric pituitaries. About 80 cases have been transmitted by contaminated dural grafts, corneal transplants and contaminated electrodes . These and the new variant cases from England are the bulk of </B><B>transmitted</B><B> cases.</B><FONT SIZE="3" COLOR="#990000" FACE="Arial" ><B> </B></FONT></div> <div> <B>The vast majority of CJD cases are </B><B>sporadic </B><B>and apparently spontaneous. The etiology of these cases is unknown. The new variant of CJD from BSE has raised the specter of food contamination as a possible cause but there is no evidence that sporadic CJD is caused by that mechanism. No mutation of the PrP gene has been identified in sporadic CJD. However, the PrP gene shows a polymorphism at codon 129 that can code for either Methionine or Valine. Most patients with sporadic and transmitted CJD are either M/M or V/V homozygotes.</B><FONT SIZE="3" COLOR="#990000" FACE="Arial" ><B> </B></FONT></div> <div> <B>The potential of</B><B> accidental transmissio</B><B>n of a fatal neurological disorder has scared pathologists and other health care workers connected with these diseases. This potential should not be underestimated. However, these fears may be somewhat exaggerated. The disease is transmitted only by invasive methods such as inoculation or injection and not by casual contact such as occurs in the course of routine patient care. An autopsy can be safely done using precautions. Fixation of tissues in formalin does not eliminate transmissibility of CJD and other prion diseases. Additional chemical treatment with phenol or formic acid is needed.</B><FONT SIZE="3" COLOR="#990000" FACE="Arial" ><B> </B></FONT></div> <div> <B>Before prions were known, sporadic CJD and other prion diseases were thought to be "degenerative" diseases. When it was discovered that they can be transmitted, they were reclassified as infectious diseases. At one point, they were called slow virus diseases. However, they are obviously not the same as bacterial or viral infections. For one thing, prions contain no nucleic acid and their chemistry and structure are not like that of bacteria or viruses. They damage neurons directly and do not elicit inflammatory and immune reactions. The familial forms of prion diseases can probably be conceived of as inherited metabolic disorders, not unlike Huntington disease or familial Alzheimer disease.The transmitted and sporadic forms are difficult to understand. How an abnormal protein entering the body crosses the blood-brain barrier and causes its normal counterparts in neurons to change their folding in a chain reaction that eventually destroys the brain, defies molecular explanation. Prions have been compared to the Borg, an alien mechano-anthropoid species in Star Trek, that relentlessly assimilate other species with which they come in contact. Two Nobel prizes have been awarded for research in prion diseases. In 1976, Carleton Gajdusek received the prize for proving that they are transmissible and in 1997 Stanley Prusiner was given the prize for the prion hypothesis.</B><FONT SIZE="3" COLOR="#990000" FACE="Arial" ><B> </B></FONT></div> <bR> <bR> </td> </tr></table></body>