The Central Nervous System

The principal functional unit of the central

nervous system (CNS) is the neuron.
Acute neuronal injury (red neurons)
- Refers to a spectrum of changes that
accompany acute CNS
hypoxia/ischemia or other acute
insults and refect cell death either
necrosis or apoptosis
- Red neurons are evident !ith
hemato"ylin and eosin (#$%)
preparations at a&out '( to () hours
after an irreversi&le hypo"ic*ischemic
insult+
- The morphologic features consist of
shrinkage of the cell body
pyknosis of the nucleus
disappearance of the nucleolus
and loss of Nissl substance !ith
intense eosinophilia of the
cytoplasm.
Subacute and chronic neuronal injury
(degeneration)
- Refers to neuronal death occurring as
a result of a progressive disease
process of some duration as is seen in
certain slo!ly evolving neurologic
diseases such as amyotrophic lateral
sclerosis (,-S)+
- The characteristic histologic feature is
cell loss often selectively involving
functionally related groups of neurons
and reactive gliosis+
- The associated reactive glial
changes are often the &est indicator
of the pathologic process+
- Neuronal trans-synaptic
degeneration is seen !hen there is a
destructive process that interrupts the
ma.ority of the a/erent input to a
group of neurons+
Axonal reaction
- Refers to the reaction !ithin the cell
&ody that attends regeneration of
the aon
- it is &est seen in anterior horn cells
of the spinal cord !hen motor a"ons
are cut or seriously damaged+
- There is increased protein
synthesis associated !ith a"onal
sprouting+
- This is refected in enlargement and
rounding up of the cell body
peripheral displacement of the
nucleus enlargement of the
nucleolus and dispersion of Nissl
substance from the center to the
periphery of the cell (central
chromatolysis)+
Neuronal inclusions
- may occur as a manifestation of
aging !hen there are
intracytoplasmic accumulations of
comple lipids (lipofuscin)!
proteins! or carbohydrates.
000 1iral infection can lead to a&normal
intranuclear inclusions! as seen in
herpetic infection "Co#dry body$!
cytoplasmic inclusions! as seen in
rabies "Negri body$! or &oth nucleus and
cytoplasm as in cytomegalovirus "C%&$
infection.
neuro2&rillary tangles - Al'heimer
disease
-e!y &odies - (arkinson disease
,&normal vacuoli3ation of the
peri4aryon and neuronal cell processes
in the neuropil - Creut'feldt-)akob
disease
000 The visi&le aggregates are not the &asis
of cellular in.uries5 rather small multimers of
the proteins (oligomers) are the critical
mediators of the damage
Reactions of Astrocytes to *njury
,strocyte
- star-shaped appearance
- cells that have multipolar &ranching
cytoplasmic processes that emanate
from the cell &ody and contain the
glial +brillary acidic protein
",-A($ a cell type6speci2c
intermediate 2lament
- act as meta&olic &u/ers and
deto"i2ers !ithin the &rain
- contri&ute to &arrier functions
controlling the fo! of macromolecules
&et!een the &lood the cere&rospinal
fuid (CS7) and the &rain through the
foot processes
Gliosis (or astrogliosis)
- is the most important histopathologic
indicator of CNS in.ury regardless of
etiology and is characteri3ed &y &oth
hypertrophy and hyperplasia+
- The nuclei of astrocytes !hich are
typically round to oval ('8 9m !ide)
!ith evenly dispersed pale chromatin
enlarge become vesicular! and
develop prominent nucleoli.
- The previously scant cytoplasm
e"pands to a bright pink some!hat
irregular s#ath around an
eccentric nucleus from !hich
emerge numerous stout ramifying
processes5 these cells are called
gemistocytic astrocytes.
Alzheimer type II astrocyte
- :s a gray-matter cell !ith a large (t!o
to three times normal) nucleus pale-
staining central chromatin an
intranuclear glycogen droplet and a
prominent nuclear mem&rane and
nucleolus+
- it is mainly seen not in ,l3heimer
disease &ut in individuals #ith long-
standing hyperammonemia due to
chronic liver disease .ilson
disease or hereditary metabolic
disorders of the urea cycle.
Reactions of /ther ,lial Cells to *njury
000 oligodendrocytes and ependyma do not
participate in the active response to CNS
in.ury and sho! a more limited repertoire of
reactions
;ligodendroglial cytoplasmic processes !rap
around e"ons and form myelin.
:n.ury or apoptosis of oligodendroglial cells is
a feature of ac<uired demyelinating
disorders and leu4odystrophies
Glial cytoplasmic inclusions primarily
composed of 0-synuclein are found in
oligodendrocytes in multiple system atrophy
(=S,)+
1pendymal cells
- the ciliated columnar epithelial cells
lining the ventricles
- do not have speci2c patterns of
reaction
- >isruption of the ependymal lining is
paired #ith proliferation of
subependymal astrocytes to
produce small irregularities on the
ventricular surfaces (ependymal
granulations)+
Reactions of %icroglia to *njury
%icroglias are mesoderm-deried cells
!hose primary function is to serve as a
+ed macrophage system in the CNS
They respond to in.ury &y?
@roliferating
developing elongated nuclei (rod
cells) as in neurosyphilis5
forming aggregates a&out small foci of
tissue necrosis (microglial nodules)
()) congregating around cell &odies of
dying neurons (neuronophagia)+
000 blood-derived macrophages are the
principal phagocytic cells present in
infammatory foci+
The &rain and spinal cord are protected &y
the rigid compartment de2ned &y the skull
vertebral bodies and dura mater+
C1R12RA3 141%A "brain parenchymal
edema$
!asogenic edema
- Caused &y blood-brain barrier
disruption and increased vascular
permeability allo!ing fuid to shift
from the intravascular
compartment to the intercellular
spaces of the &rain+
- may &e either locali3ed (e+g+ ad.acent
to infammation or neoplasms) or
generali3ed+
Cytotoxic edema
- is an increase in intracellular 5uid
secondary to neuronal! glial! or
endothelial cell membrane injury
as might &e encountered in someone
!ith a generali3ed hypo"ic*ischemic
insult or !ith meta&olic damage
*nterstitial edema "hydrocephalic
edema$
- occurs especially around the lateral
ventricles !hen an increase in
intravascular pressure causes an
a&normal fo! of fuid from the
intraventricular CS7 across the
ependymal lining to the periventricular
!hite matter+
,enerali'ed edema
- the gyri are 5attened the
intervening sulci are narro#ed and
the ventricular cavities are
compressed.
674R/C1(6A38S
- accumulation of e"cessive CS7 !ithin
the ventricular system
- most cases occur as a conse<uence of
impaired 5o# and resorption of
CS-5 only rarely is overproduction the
cause of hydrocephalus
000 Ahen hydrocephalus develops in infancy
before closure of the cranial sutures
there is enlargement of the head+
#ydrocephalus developing after this period
in contrast is associated !ith epansion of
the ventricles and increased
intracranial pressure !ithout a change in
head circumference+
Noncommunicating hydrocephalus
- only a portion of the ventricular
system is enlarged &ecause of e"cess
CS7
- may occur &ecause of a mass in the
third ventricle
communicating hydrocephalus
- there is enlargement of the entire
ventricular system
hydrocephalus ex acuo
- Refers to dilation of the ventricular
system !ith a compensatory increase
in CS7 volume secondary to a loss of
&rain parenchyma+
RA*S14 *NTRACRAN*A3 (R1SS8R1 AN4
61RN*AT*/N
The cranial vault is divided &y rigid dural
folds (the fal and tentorium)+
"erniation syndrome localized
expansion of the brain is sufciently severe
Su#falcine (cingulate) herniation
- occurs !hen unilateral or asymmetric
e"pansion of a cere&ral hemisphere
displaces the cingulate gyrus under
the fal" cere&ri+
- This may lead to compression of
&ranches of the anterior cere&ral
artery+
$ranstentorial (uncinate% mesial
temporal) herniation
- occurs !hen the medial aspect of the
temporal lo&e is compressed against
the free margin of the tentorium+
- the third cranial nerve is
compromised resulting in pupillary
dilation and impairment of ocular
movements on the side of the lesion+
- The posterior cere&ral artery may also
&e compressed resulting in ischemic
in.ury to the territory supplied &y that
vessel including the primary visual
corte"+
- Ahen the e"tent of herniation is large
enough the contralateral cere&ral
peduncle may &e compressed
resulting in hemiparesis ipsilateral to
the side of the herniation5 the change
in the peduncle in this setting is
kno#n as &ernohan's notch.
000 #emorrhagic lesions in the mid&rain and
pons is termed as secondary brainstem or
Duret hemorrhages
$onsillar herniation
- Refers to displacement of the
cere&ellar tonsils through the foramen
magnum+
- :s life-threatening &ecause it causes
&rainstem compression and
compromises vital respiratory and
cardiac centers in the medulla
o&longata+
=alformations and >evelopmental >iseases
N18RA3 T821 41-1CTS
1ncephalocele
- is a diverticulum of malformed CNS
tissue e"tending through a defect in
the cranium+
- :t most often occurs in the occipital
region or in the posterior fossa+
000 The most common neural tu&e defects
involve the spinal cord and are caused &y a
failure of closure or &y reopening of the
caudal portions of the neural tu&e
Spinal dysraphism or spina #i(da
- may &e an asymptomatic &ony defect
(spina &i2da occulta) or a severe
malformation !ith a fattened
disorgani3ed segment of spinal cord
associated !ith an overlying
meningeal outpouching+
)yelomeningocele "or
meningomyelocele$
- refers to e"tension of CNS tissue
through a defect in the verte&ral
column5
- the term meningocele applies !hen
there is only a meningeal e"trusion+
- occur most commonly in the
lum&osacral region and a/ected
individuals manifest clinical de2cits
refera&le to motor and sensory
function in the lo!er e"tremities as
!ell as distur&ances of &o!el and
&ladder control+
000 The concordance rate of neural tu&e
defects is high among mono3ygotic t!ins
>e2ciency during the initial !ee4s of
gestation has &een implicated as a ris4
factor+
Anencephaly
- is a malformation of the anterior end
of the neural tu&e !ith a&sence of the
&rain and calvarium+
- 7ore&rain development is disrupted at
appro"imately (B days of gestation
and all that remains in its place is the
area cere#roasculosa a fattened
remnant of disorgani3ed &rain tissue
!ith admi"ed ependyma choroid
ple"us and meningothelial cells+
-/R12RA*N AN/%A3*1S
microencephaly is more common than
megalencephaly
*issencephaly (agyria)
- noticea&le decrease in the num&er of
gyri to total a&sence leaving a
smooth-surfaced &rain
- ;ne of the &est understood causes is
mutations in the gene encoding the
microtubule-associated protein
3*S-9
- also occur from a series of mutations
in the genes encoding en'ymes
responsible for the glycosylation
of 0-dystroglycan
+olymicrogyria
- is characteri3ed &y small unusually
numerous and irregularly formed
cere&ral convolutions+
- can &e induced &y locali3ed tissue
in.ury to!ard the end of neuronal
migration although genetically
determined forms !hich are typically
&ilateral and symmetric are also
recogni3ed
Neuronal heterotopias
- are a group of migrational disorders
that are commonly associated !ith
epilepsy
- consist of collections of neurons in
inappropriate locations along the
migrational path!ays
- one location in !hich heterotopias can
&e found is along the ventricular
surface
- (eriventricular heterotopias can
&e caused &y mutations in the gene
encoding +lamin A an actin-&inding
protein responsi&le for assem&ly of
comple" mesh!or4s of 2laments (This
gene is on the X chromosome, and the
mutant allele causes male lethality)
doublecortin (DX)
- microtu&ule-associated protein
- mutations in this gene result in
lissencephaly in males and in
su&cortical &and heterotopias in
females
"oloprosencephaly
- is a spectrum of malformations
characteri3ed &y incomplete
separation of the cere&ral
hemispheres across the midline+
- Severe forms manifest midline facial
a&normalities including cyclopia5
- -ess severe variants
"arrhinencephaly$ sho! a&sence of
the olfactory cranial nerves and
related structures
- #oloprosencephaly is associated !ith
trisomy 9: as !ell as other genetic
syndromes+
- =utations a/ecting sonic hedgehog
protein or its signaling path!ay may
result in holoprosencephaly+
Agenesis of the corpus callosum
- a&sence of the !hite matter &undles
that carry cortical pro.ections from one
hemisphere to the other
- misshapen lateral ventricles (&at-
!ing deformity)
- can &e associated !ith mental
retardation or may occur in clinically
normal individuals
(/ST1R*/R -/SSA AN/%A3*1S
,andy--al.er malformation
- is characteri3ed &y an enlarged
posterior fossa+
- :n the place of cere&ellar vermis is a
large midline cyst that is lined &y
ependyma and is contiguous !ith
leptomeninges on its outer surface
- >ysplasias of &rainstem nuclei are
commonly found in association !ith
>andy-Aal4er malformation+
Arnold-Chiari malformation (Chiari type
II malform/)
- consists of a small posterior fossa
a misshapen midline cerebellum
!ith do!n!ard e"tension of vermis
through the foramen magnum and
almost invaria&ly hydrocephalus
and a lumbar myelomeningocele.
- !n Chiari type I malformation lo!-
lying cere&ellar tonsils e"tend do!n
into the verte&ral canal+
"ydromyelia
- characteri3ed &y a discontinuous
multisegmental or confuent e"pansion
of the ependyma-lined central canal of
the cord
Syringomyelia
- characteri3ed &y the formation of a
fuid-2lled cleftli4e cavity in the inner
portion of the cord% that may e"tend
into the &rainstem (syringo#ul#ia).
- may &e associated !ith the Chiari :
malformation
@erinatal Crain :n.ury
cere#ral palsy
- refers to a nonprogressive neurologic
motor de2cit characteri3ed &y
com&inations of spasticity dystonia
ata"ia*athetosis and paresis
attri&uta&le to insults occurring during
the prenatal and perinatal periods
perientricular leu.omalacia
- :nfarcts in the supratentorial
periventricular !hite matter
- are chal4y yello! pla<ues consisting of
discrete regions of !hite matter
necrosis and calci2cation
multicystic encephalopathy
- condition !hen &oth gray and !hite
matter are involved &y e"tensive
ischemic damage
- large destructive cystic lesions
develop throughout the hemispheres
Trauma
S;833 -RACT8R1S
displaced s.ull fracture
- fracture in !hich &one is displaced
into the cranial cavity &y a distance
greater than the thic4ness of the &one
000 Dsual site of impact?
Ahen a!a4e 6 occipital part of s4ull
Ahen unconscious 6 frontal part of
s4ull
000 7ractures that cross sutures are termed
diastatic
(AR1NC67%A3 *N)8R*1S
Concussion
- is a clinical syndrome of altered
consciousness secondary to head
in.ury typically &rought a&out &y a
change in the momentum of the head
- Characteristic neurologic picture
includes instantaneous onset of
transient neurologic dysfunction
including loss of consciousness
temporary respiratory arrest and
loss of re5ees.
- amnesia for the event persists
4irect (arenchymal *njury
Contusion and laceration are lesions
associated !ith direct parenchymal in.ury of
the &rain
, person !ho su/ers a &lo! to the head may
develop a contusion at the point of contact
(a coup injury) or a contusion on the &rain
surface diametrically opposite to it (a
contrecoup injury)+
TRA8%AT*C &ASC83AR *N)8R7
- results from direct trauma and
disruption of the vessel !all and leads
to hemorrhage
- hemorrhage may occur in the
epidural! su#dural! su#arachnoid!
and intraparenchymal
compartments sometimes in
com&ination
- Subarachnoid and
intraparenchymal hemorrhages
most often occur concomitantly in
the setting of &rain trauma that also
results in super2cial contusions and
lacerations
acute subdural hematoma
- appears as a collection of freshly
clotted &lood along the &rain surface
!ithout e"tension into the depths of
sulci

3ysis of the clot (a&out ' !ee4)


,ro#th of +broblasts from the dural surface
into the hematoma (( !ee4s)


%arly development of hyalini'ed connective
tissue (' to E months)
S(*NA3 C/R4 TRA8%A
lesions involving the?
thoracic vertebrae or belo# -
paraplegia5
cervical lesions - <uadriplegia5
above C< - lead to respiratory
compromise from paralysis of the
diaphragm+
Cere&rovascular >iseases
- third leading cause of death (after
heart disease and cancer) in the
Dnited States
- most prevalent neurologic disorder in
terms of &oth mor&idity and mortality+
- three ma.or categories! thrombosis
embolism and hemorrhage
- =Stroke> is the clinical designation
that applies to all these conditions
particularly !hen symptoms &egin
acutely
Cere&rovascular disease t!o processes?
6ypoia! ischemia! and infarction
resulting from impairment of &lood
supply and o"ygenation of CNS tissue
6emorrhage resulting from rupture
of CNS vessels
000 The &rain receives 9?@ of the resting
cardiac output and accounts for AB@ of
the total body oygen consumption.
T!o principal types of acute ischemic in.ury?
Glo#al cere#ral ischemia
(ischemic*hypo"ic encephalopathy)
occurs !hen there is a generali3ed
reduction of cere&ral perfusion as in
cardiac arrest shoc4 and severe
hypotension+
1ocal cere#ral ischemia follo!s
reduction or cessation of &lood fo! to
a locali3ed area of the &rain due to
large-vessel disease or to small-vessel
disease+
2order zone (34atershed5) infarcts
- ;ccur in the regions of the &rain or
spinal cord that lie at the most distal
reaches of the arterial &lood supply
the &order 3ones &et!een arterial
territories+
- &order 3one &et!een the anterior
and the middle cerebral artery
distri&utions is at greatest ris4
- >amage to this region produces a
sickle-shaped band of necrosis
- usually seen after hypotensive
episodes
Infarction from 6#struction of *ocal
2lood Supply
(1ocal Cere#ral Ischemia)
- The ma.or source of collateral fo! is
the circle of .illis (supplemented &y
the e"ternal carotid-ophthalmic
path!ay)+
- The ma"ority of thrombotic occlusions
are due to atherosclerosis
- =ost common sites of primary
throm&osis causing cere&ral infarction
are the carotid bifurcation the
origin of the middle cerebral
artery and either end of the basilar
artery+
000 Cardiac mural thrombi are among the
most common sources of em&olism in the
&rain5 myocardial infarct valvular
disease and atrial +brillation are
important predisposing factors+
000 +rimary angiitis of the CNS is an
infammatory disorder that involves multiple
small- to medium-si3ed parenchymal and
su&arachnoid vessels and is characteri3ed &y
chronic infammation multinucleated giant
cells and destruction of the vessel !all+
( groups of infarcts &ased on presence of
infarcts?
"emorrhagic (red) infarction -
characteri3ed &y multiple sometimes
confuent petechial hemorrhages is
typically associated !ith em&olic
events+
- secondary to reperfusion of damaged
vessels and tissue either through
collaterals or directly after dissolution
of intravascular occlusive material
nonhemorrhagic (pale% #land%
anemic) infarcts - are usually
associated !ith throm&osis
000 Thrombolytic therapy may &e used in
cases of throm&osis &ut is contraindicated
in hemorrhagic infarcts+
67(1RT1NS*&1 C1R12R/&ASC83AR 4*S1AS1
The most important e#ects of hypertension
on the brain include lacunar infarcts, slit
hemorrhages, and hypertensie
encephalopathy, as $ell as massie
hypertensie intracere#ral hemorrhage.
3acunar *nfarcts
- 3acunae - are la4e-li4e spaces less
than 'F mm !ide !hich occur in the
lenticular nucleus thalamus internal
capsule deep !hite matter caudate
nucleus and pons in descending
order of fre<uency+
- they consist of areas of tissue loss
!ith scattered lipid-laden
macrophages and surrounding gliosis
Slit 6emorrhages
- #ypertension also gives rise to
rupture of the small-caliber
penetrating vessels and the
development of small
hemorrhages+
- :n time these hemorrhages resor&
leaving &ehind a slitlike cavity (slit
hemorrhage) surrounded by
bro#nish discoloration
6ypertensive 1ncephalopathy
- is a clinicopathologic syndrome arising
in an individual !ith malignant
hypertension and is characteri3ed
&y diCuse cerebral dysfunction
including headaches confusion
vomiting and convulsions
sometimes leading to coma
- @etechiae and 2&rinoid necrosis of
arterioles in the gray and !hite matter
- (ostmortem? edematous &rain !ith
or !ithout transtentorial or tonsillar
herniation
!ascular (multi-infarct) dementia
- a distinctive clinical syndrome
characteri3ed &y dementia gait
a&normalities and pseudo&ul&ar
signs often !ith superimposed focal
neurologic de2cits
- multiple &ilateral gray matter
(corte" thalamus &asal ganglia) and
#hite matter (centrum semiovale)
infarcts
- is caused &y multifocal vascular
disease of several types including (')
cerebral atherosclerosis (() vessel
thrombosis or emboli'ation from
carotid vessels or from the heart and
(E) cerebral arteriolar sclerosis
from chronic hypertension+
000 2ins4anger disease !hen the pattern
of in.ury preferentially involves large areas of
the su&cortical !hite matter !ith myelin and
a"on loss
*NTRACRAN*A3 61%/RR6A,1
*ntracerebral "*ntraparenchymal$
6emorrhage
- The t!o ma.or underlying etiologies of
this form of cere&rovascular disease
are hypertension and cerebral
amyloid angiopathy "CAA$.
- "ypertension is the most common
underlying cause of primary brain
parenchymal hemorrhage
- CAA is a condition in !hich
amyloidogenic peptides nearly al!ays
the same one found in ,l3heimer
disease deposit in the !alls of
medium- and small-cali&er meningeal
and cortical vessels+
Cere#ral autosomal dominant
arteriopathy 4ith su#cortical infarcts
and leu.oencephalopathy "CA4AS*3$
- is a rare hereditary form of stro4e
caused &y mutations in the gene
encoding the Notch: receptor
- characteri3ed clinically &y recurrent
strokes (usually infarcts less often
hemorrhages) and dementia
- abnormalities of #hite matter and
leptomeningeal arteries consisting
of concentric thickening of the
media and adventitia.
- Casophilic @,S-positive deposits
Subarachnoid 6emorrhage and
Ruptured Saccular Aneurysms
- The most fre<uent cause of clinically
signi2cant subarachnoid
hemorrhage is rupture of a saccular
"#erry) aneurysm
- Su&arachnoid hemorrhage may also
result from e"tension of a traumatic
hematoma rupture of a hypertensive
intracere&ral hemorrhage into the
ventricular system vascular
malformation hematologic
distur&ances and tumors+
000 Saccular aneurysm is the most
common type of intracranial aneurysm
%ycotic! Traumatic! and 4issecting -
li4e saccular aneurysms are most often
found in the anterior circulation &ut di/er in
that they more often cause cere&ral
infarction rather than su&arachnoid
hemorrhage+
&ascular %alformations
000 arterioenous and caernous
malformations are associated !ith ris4 of
hemorrhage and development of neurologic
symptoms+
Arteriovenous malformations (,1=)
- =ost common malformation
- involve vessels in the su&arachnoid
space e"tending into &rain
parenchyma or may occur e"clusively
!ithin the &rain+
- has prominent pulsatile arteriovenous
shunting !ith high &lood fo!+
- They are composed of greatly
enlarged &lood vessels separated &y
gliotic tissue often !ith evidence of
prior hemorrhage+
Cavernous malformations
- consist of greatly distended loosely
organi3ed vascular channels !ith thin
collageni3ed !alls and are devoid of
intervening nervous tissue
- They occur most often in the
cere&ellum pons and su&cortical
regions in decreasing order of
fre<uency
- have a lo! fo! !ithout arteriovenous
shunting+
- -oci of old hemorrhage infarction
and calci+cation fre<uently surround
the a&normal vessels
Capillary telangiectasias
- are microscopic foci of dilated thin-
!alled vascular channels separated &y
relatively normal &rain parenchyma
and occurring most fre<uently in the
pons
&enous angiomas (varices)
- consist of aggregates of ectatic
venous channels+
- -oi-Alajouanine disease
(angiodysgenetic necroti3ing
myelopathy) is a venous angiomatous
malformation of the spinal cord and
overlying meninges most often in the
lum&osacral region associated !ith
ischemic myelomalacia and slo!ly
progressive neurologic symptoms+
:nfections
"ematogenous spread
- is the most common means of entry
- infectious agents ordinarily enter
through the arterial circulation &ut
retrograde venous spread can occur
through anastomoses !ith veins of the
face+
,irect implantation of microorganisms
- is almost invaria&ly traumatic or is
associated !ith congenital
malformations
AC8T1 %1N*N,*T*S
)eningitis
- refers to an infammatory process of
the leptomeninges and CS7 !ithin the
su&arachnoid space
- =eningitis is usually caused &y an
infection &ut may also occur in
response to a non&acterial irritant
introduced into the su&arachnoid
space
)eningoencephalitis
- Com&ined meningitis !ith
infammation of the &rain
parenchyma+
Acute (yogenic "2acterial$ %eningitis
*n neonates - %scherichia coli and the group
C streptococci
At etreme of life - &treptococcus
pneumoniae and 'isteria monocytogenes
Among adolescents and in young adults
- (eisseria meningitidis
Acute Aseptic "&iral$ %eningitis
- :s a clinical term referring to the
a&sence of recogni3a&le organisms in
a patient !ith meningeal irritation
fever and alterations of consciousness
of relatively acute onset+
AC8T1 -/CA3 S8((8RAT*&1 *N-1CT*/NS
2rain Abscess
- may arise &y direct implantation of
organisms local etension from
adjacent foci (mastoiditis paranasal
sinusitis) or hematogenous spread
(usually from a primary site in the
heart lungs or distal &ones or after
tooth e"traction)+
@redisposing conditions include?
'+ acute #acterial endocarditis
)/ congenital heart disease !ith right-to-
left shunting and loss of pulmonary 2ltration
of organisms
E+ chronic pulmonary sepsis - seen !ith
&ronchiectasis
)+ immunosuppression
000 Streptococci and staphylococci are
the most common o/ending organisms
identi2ed in nonimmunosuppressed
populations+
Subdural 1mpyema
- caused &y &acterial or occasionally
fungal infection of the s4ull &ones or
air sinuses that can spread to the
su&dural space
1tradural Abscess
- commonly associated !ith
osteomyelitis often arises from an
ad.acent focus of infection such as
sinusitis or a surgical procedure
- 4hen the process occurs in the
spinal epidural space it may cause
spinal cord compression and
constitute a neurosurgical emergency
C6R/N*C 2ACT1R*A3 %1N*N,/1NC1(6A3*T*S
Chronic &acterial infection of the meninges
and the &rain may &e caused &y )/
tu#erculosis! $/ pallidum! and 2orrelia
species
Tuberculosis
- the su&arachnoid space contains a
gelatinous or 2&rinous e"udate most
often at the &ase of the &rain
o&literating the cisterns and encasing
cranial nerves+
- The most common pattern of
involvement is a di/use
meningoencephalitis
- symptoms of headache malaise
mental confusion and vomiting
Neurosyphilis
- is a manifestation of the tertiary stage
of syphilis and occurs in only a&out
'8G of individuals !ith untreated
infection
- The ma.or patterns of CNS
involvement are meningovascular
neurosyphilis paretic
neurosyphilis and tabes dorsalis
%eningovascular neurosyphilis
- is a chronic meningitis involving the
&ase of the &rain and more varia&ly
the cere&ral conve"ities and the spinal
leptomeninges+
- there may &e an associated
obliterative endarteritis "6eubner
arteritis$ accompanied &y a
distinctive perivascular infammatory
reaction rich in plasma cells and
lymphocytes+
- Cerebral gummas "plasma cellD
rich mass lesions$ may also occur in
the meninges and e"tend into the
parenchyma+
(aretic neurosyphilis
- is caused &y invasion of the &rain &y
Treponema pallidum and is clinically
manifested as insidious &ut
progressive mental de2cits associated
!ith mood alterations (including
delusions of grandeur) that terminate
in severe dementia "general paresis
of the insane$+
Tabes dorsalis
- is the result of damage &y the
spirochetes to the sensory nerves in
the dorsal roots !hich produces
impaired .oint position sense and
resultant ata"ia (locomotor ata"ia)5
- loss of pain sensation leading to s4in
and .oint damage (Charcot .oints)5
Neuroborreliosis "3yme 4isease$
- is caused &y the spirochete *orrelia
burgdorferi transmitted &y various
species of !xodes tic45 involvement of
the nervous system is referred to as
neuro&orreliosis+
- Neurologic symptoms? aseptic
meningitis facial nerve palsies and
other polyneuropathies as !ell as
encephalopathy+
- focal proliferation of microglial cells in
the &rain as !ell as scattered
e"tracellular organisms
&*RA3 %1N*N,/1NC1(6A3*T*S
- is a parenchymal infection of the &rain
almost invaria&ly associated !ith
meningeal in5ammation
"meningoencephalitis$ and
sometimes !ith simultaneous
involvement of the spinal cord
"encephalomyelitis$.
6erpes Simple &irus Type 9
- is most common in children and young
adults
- The most commonly o&served clinical
presenting symptoms in herpes
encephalitis are alterations in mood
memory and &ehavior
6erpes Simple &irus Type A
- in adults it causes meningitis
- as many as F8G of neonates &orn &y
vaginal delivery to !omen !ith active
primary #S1 genital infections ac<uire
the infection during passage through
the &irth canal and develop severe
encephalitis
Cytomegalovirus
- This infection of the nervous system
occurs in fetuses and
immunosuppressed individuals+
- The outcome of infection in utero is
periventricular necrosis that
produces severe &rain destruction
follo!ed later &y microcephaly and
periventricular calci+cation+
- C=1 is a common opportunistic viral
pathogen in individuals !ith ,:>S !ith
CNS involvement &eing common in
this setting+
(oliomyelitis
- a/ects the motor neurons of the spinal
cord it produces a faccid paralysis
!ith muscle !asting and hyporefe"ia
in the corresponding region of the
&odyHthe permanent neurologic
residue of poliomyelitis+
- :n the acute disease death can occur
from paralysis of the respiratory
muscles and a myocarditis
sometimes complicates the clinical
course
Rabies
- is a severe encephalitis transmitted to
humans &y the &ite of a ra&id animal
usually a dog or various !ild mammals
that form natural reservoirs
6uman *mmunode+ciency &irus
- is &est characteri3ed microscopically
as a chronic infammatory reaction
!ith !idely distri&uted in2ltrates of
microglial nodules sometimes !ith
associated foci of tissue necrosis and
reactive gliosis
- ,n important component of the
microglial nodule is the macrophage-
derived multinucleated giant cell+
(rogressive %ultifocal
3eukoencephalopathy
- is a viral encephalitis caused &y the IC
polyomavirus5
- &ecause the virus preferentially infects
oligodendrocytes demyelination is
its principal pathologic e#ect+
- lesions consist of patches of irregular
ill-de2ned destruction of the !hite
matter ranging in si3e from millimeters
to e"tensive involvement of an entire
lo&e of the &rain
Subacute Sclerosing (anencephalitis
- (SS@%) is a rare progressive clinical
syndrome characteri3ed &y cognitive
decline spasticity of lim&s and
sei3ures+ :t occurs in children or young
adults months or years after an initial
early-age acute infection !ith measles
- represents persistent &ut
nonproductive infection of the CNS &y
an altered measles virus5 changes in
several viral genes have &een
associated !ith the disease
- #idespread gliosis and myelin
degeneration5 viral inclusions
largely !ithin the nuclei of
oligodendrocytes and neurons5
varia&le in5ammation of #hite and
gray matter5 and neuro+brillary
tangles
-8N,A3 %1N*N,/1NC1(6A3*T*S
7ungusE Candida albicans! %ucor
species! Aspergillus fumigatus! and
Cryptococcus neoformans
three main patterns of fungal infection in the
CNS? chronic meningitis! vasculitis! and
parenchymal invasion
&asculitis is most fre<uently seen !ith
mucormycosis and aspergillosis &oth of
!hich are characteri3ed &y direct fungal
invasion of blood vessel #alls &ut it
occasionally occurs !ith other infections
such as candidiasis+
The most commonly encountered fungi
invading the &rain are Candida and
Cryptococcus.
,lthough most fungi invade the &rain &y
hematogenous dissemination direct
e"tension may also occur particularly in
mucormycosis most commonly in dia&etics
!ith 4etoacidosis+
Cryptococcal meningitis
- a common opportunistic infection in
the setting of #:1*,:>S
Transmissi&le Spongiform %ncephalopathies
(@rion >iseases)
@rion group of diseases?
Creut3feldt-Ia4o& disease (CI>) 6
most common
Jerstmann-StrKussler-Schein4er
syndrome (JSS)
fatal familial insomnia
4uru in humans
scrapie in sheep and goats
min4-transmissi&le encephalopathy
chronic !asting disease of deer and
el4
&ovine spongiform encephalopathy
,re predominantly characteri3ed &y
spongiform change caused &y
intracellular vacuoles in neurons and glia+
Clinically most of the a/ected
patients develop progressive dementia.
FFF Normal @r@ is a E8-4> cellular protein
present in neurons+ >isease occurs !hen the
@r@ undergoes a conformational change from
its normal 0-heli-containing isoform
(@r@
c
) to an abnormal G-pleated sheet
isoform! usually termed @r@
sc
+
Creut'feldt-)akob 4isease
- is a rare disorder that manifests
clinically as a rapidly progressive
dementia
- primarily sporadic
- familial forms also e"ist that are
caused &y mutations in ,-(,
- su&tle changes in memory and
&ehavior follo!ed &y a rapidly
progressive dementia often !ith
pronounced involuntary .er4ing muscle
contractions on sudden stimulation
(startle myoclonus)+
- long-surviving cases sho! e"tensive
atrophy of involved gray matter+
&ariant Creut'feldt-)akob 4isease
- the disease a/ects young adults
- &ehavioral disorders 2gured
prominently in the early stages of the
disease
- neurologic syndrome progressed more
slo!ly than in individuals !ith other
forms of CI>+
- neuropathologic 2ndings and
molecular features of these ne! cases
!ere similar to those of CI>+
- variant CI> (vCI>) is characteri3ed &y
the presence of e"tensive cortical
pla<ues !ith a surrounding halo of
spongiform change+ "No alterations
in the +7N+ gene are present$
-atal -amilial *nsomnia
- sleep distur&ances that characteri3e
its initial stage
- is also caused &y a speci2c mutation
in the ,-(, gene
- the mutation !hich leads to an
aspartate substitution for
asparagine at residue 'LB of @r@
c

results in 77: !hen it occurs in a ,-(,
allele encoding methionine at codon
'(M &ut causes CI> !hen present in
tandem !ith a valine at this position+
000 77: does not sho! spongiform pathology+
:nstead the most stri4ing alteration is
neuronal loss and reactive gliosis in the
anterior ventral and dorsomedial nuclei of
the thalamus

>emyelinating >iseases
- ,re ac<uired conditions characteri3ed
&y preferential damage to myelin !ith
relative preservation of a"ons+
- The clinical de2cits are due to the
e/ect of myelin loss on the
transmission of electrical impulses
along a"ons+
- limited capacity of the CNS to
regenerate normal myelin and &y the
degree of secondary damage to a"ons
that occurs as the disease runs its
course
%83T*(31 SC31R/S*S
- is an autoimmune demyelinating
disorder characteri3ed &y distinct
episodes of neurologic de+cits
separated in time attri&uta&le to
#hite matter lesions that are
separated in space+
- most common of the demyelinating
disorders
- lesions of =S are caused &y an
immune response that is directed
against the components of the
myelin sheath
- Dnilateral visual impairment due to
involvement of the optic nerve (optic
neuritis% retro#ul#ar neuritis) is a
fre<uent initial manifestation of =S+
N18R/%713*T*S /(T*CA
- ,eic disease
- development of synchronous (or near
synchronous) &ilateral optic neuritis
and spinal cord demyelination
- Ahite cells are common in the CS7
often including neutrophils+
- a/ected individuals sho! antibodies
to aHuaporins !hich are in part
responsi&le for maintenance of
astrocytic foot process and thus the
integrity of the &lood-&rain &arrier
Acute disseminated encephalomyelitis
- perivenous encephalomyelitis
- is a di/use monophasic demyelinating
disease that follo!s either a viral
infection or rarely a viral
immuni3ation
Acute necroti'ing hemorrhagic
encephalomyelitis
- acute hemorrhagic leu4oencephalitis
of Aeston #urst
- is a fulminant syndrome of CNS
demyelination typically a/ecting
young adults and children+
- The illness is almost invaria&ly
preceded &y a recent episode of upper
respiratory infection most often of
un4no!n cause+
- The disease is fatal in many patients
!ith signi2cant de2cits present in
most survivors+
Central pontine myelinolysis
- is characteri3ed &y loss of myelin
(!ith relative preservation of aons
and neuronal cell bodies) in a
roughly symmetric pattern involving
the &asis pontis and portions of the
pontine tegmentum &ut sparing the
periventricular and subpial
regions+
- -esions may &e found more rostrally
- most commonly associated !ith rapid
correction of hyponatremia
- myelin loss #ithout evidence of
in5ammation
>egenerative >iseases
- These are diseases of gray matter
characteri3ed &y the progressive
loss of neurons !ith associated
secondary changes in #hite
matter tracts
- presence of protein aggregates that
are resistant to degradation through
the u&i<uitin-proteasome system
( approaches in degenerative diseases?
Symptomatic/anatomic. is typically
refected in the clinical symptoms
+athologic. &ased on the types of
inclusions or a&normal structures
o&served
41,1N1RAT*&1 4*S1AS1S A--1CT*N, T61
C1R12RA3 C/RT1I
,ementia
- @rincipal clinical manifestation of
,l3heimer
- progressive loss of cognitive function
independent of the state of attention+
Al'heimer 4isease
- is the most common cause of
dementia in the elderly
- as insidious impairment of higher
intellectual function !ith alterations in
mood and &ehavior+
- -ater progressive disorientation
memory loss and aphasia &ecome
manifest indicating severe cortical
dysfunction
- the &rain sho!s a varia&le degree of
cortical atrophy mar4ed &y
#idening of the cerebral sulci that
is most pronounced in the frontal
temporal and parietal lo&es
- The fundamental abnormality in /D is
the deposition of AG peptides
!hich are derived through processing
of ,@@+
- ,@@ is a cell surface protein !ith a
single transmem&rane domain that
may function as a receptor although
ligands have remained elusive+
(ick 4isease
- -o&ar atrophy
- is a rare distinct progressive
dementia characteri3ed clinically &y
early onset of &ehavioral changes
together !ith alterations in personality
(frontal lo&e signs) and language
distur&ances (temporal lo&e signs)+
(rogressive Supranuclear (alsy
- is an illness characteri3ed clinically &y
truncal rigidity !ith dyseHuilibrium
and nuchal dystonia5
pseudobulbar palsy and abnormal
speech5 ocular disturbances
including vertical ga'e palsy
progressing to diNculty !ith all eye
movements5 and mild progressive
dementia in most a/ected individuals
- N; mutations in the 0/,T gene
Corticobasal 4egeneration
- e"trapyramidal signs and symptoms
- grouped !ith syndromes of &asal
ganglia dysfunction
- there is cortical atrophy mainly of the
motor premotor and anterior parietal
lo&es
- These regions of corte" sho! severe
loss of neurons gliosis and
=ballooned> neurons (neuronal
achromasia)+
- associated !ith 0/,T haplotype lin4ed
to progressive supranuclear palsy
41,1N1RAT*&1 4*S1AS1S /- 2ASA3 ,AN,3*A
AN4 2RA*NST1%
- 7re<uently associated !ith movement
disorders including rigidity a&normal
posturing and chorea+
- a reduction of voluntary movement or
an a&undance of involuntary
movement
000 The &asal ganglia especially the
nigrostriatal path#ay - play an important
role in the system of positive and
negative regulatory synaptic path#ays
that serve to modulate feed&ac4 from the
thalamus to the motor corte"+
(arkinsonism
- is a clinical syndrome characteri3ed &y
diminished facial epression
stooped posture slo#ness of
voluntary movement festinating
gait (progressively shortened
accelerated steps) rigidity and a
pill-rolling> tremor+
- >amage to the nigrostriatal
dopaminergic system
- may also &e induced &y drugs that
a/ect this system particularly
dopamine antagonists and to"ins
- This diagnosis is made in individuals
!ith progressive 3-4/(A-
responsive signs of par4insonism
(tremor rigidity and &rady4inesia) in
the absence of a toic or other
kno#n underlying etiology
@rincipal diseases that involve the
nigrostriatal system?
@ar4inson disease
=ultiple system atrophy
@ostencephalitic par4insonism
@rogressive supranuclear palsy and
cortico&asal degeneration
multiple system atrophy ")SA$
- descri&es a group of disorders
characteri3ed &y the presence of glial
cytoplasmic inclusions typically !ithin
the cytoplasm of oligodendrocytes
that can have di/erent patterns of
clinical presentation+
- The dominant symptoms can &e
parkinsonism or cerebellar
dysfunction or autonomic
dysfunction.
- ;f these %SA-C "cerebellar
dysfunction$ is the least fre<uently
o&served pure syndrome+
6untington 4isease
- is an autosomal dominant disease
characterized clinically by
progressie moement disorders
and dementia, and histologically by
degeneration of striatal neurons+
- Ier4y hyper4inetic sometimes
dystonic movements involving all
parts of the &ody (chorea) are
characteristic+
- is the prototype of the polyglutamine
trinucleotide repeat e"pansion
diseases
- 1huntingtin2
- +athogenesis8 The loss of medium
spiny striatal neurons leads to
dysregulation of the &asal ganglia
circuitry that modulates motor output+
These neurons normally function to
dampen motor activity5 thus their
degeneration in #> results in
increased motor output often
manifested as choreoathetosis+
S(*N/C1R12133AR 41,1N1RAT*/NS
- ,/ects the cere&ellar corte" spinal
cord peripheral nerves and other
regions of the neura"is
Spinocerebellar Ataias
- group of genetically distinct diseases
characteri3ed &y signs and symptoms
refera&le to the cere&ellum
(progressive ata"ia) &rainstem spinal
cord and peripheral nerves as !ell as
other &rain regions in di/erent
su&types+
- characteri3ed &y neuronal loss from
the a/ected areas and secondary
degeneration of !hite-matter tracts
Ataia-Telangiectasia
- an autosomal recessive disorder
characteri3ed &y an ataic-
dyskinetic syndrome &eginning in
early childhood !ith the su&se<uent
development of telangiectasias in
the conjunctiva and skin5 and
immunode2ciency
- ataia-telangiectasia mutated
"A$)$ gene on chromosome ''<((6
<(E encodes a 4inase !ith a critical
role in orchestrating the cellular
response to dou&le-stranded >N,
breaks
41,1N1RAT*&1 4*S1AS1S A--1CT*N,
%/T/R N18R/NS
- group of inherited or sporadic diseases
that a/ect &oth lo!er motor neurons
in the anterior horns of the spinal cord
and &rainstem motor nuclei and upper
motor neurons in the motor corte"
(also 4no!n as 2et' cells$.
Amyotrophic 3ateral Sclerosis "A3SJ
%otor Neuron 4isease$
- characteri3ed &y loss of lo!er motor
neurons in spinal cord and &rainstem
and upper motor neurons that pro.ect
in corticospinal tracts
2ulbospinal Atrophy ";ennedy
Syndrome$
- I-linked adult-onset disease is
characteri3ed &y distal limb
amyotrophy and bulbar signs such
as atrophy and fasciculations of
the tongue and dysphagia
- androgen insensitivity gynecomastia
testicular atrophy and oligospermia
Spinal %uscular Atrophy
- group of diseases a/ects mainly the
lo!er motor neurons in children+
- ,s in ,-S there is a selective loss of
anterior-horn cells and atrophy of
anterior spinal roots.
Jenetic =eta&olic >iseases
Neuronal storage diseases
- are mostly autosomal recessive
disorders caused &y the de2ciency of
a speci2c en3yme involved in the
cata&olism of sphingolipids
mucopolysaccharides or mucolipids+
- characteri3ed &y the accumulation of
the su&strate of the en3yme !ithin the
lysosomes of neurons leading to
neuronal death+
- may also cause sei3ures
*eu.odystrophies
- are characteri3ed &y myelin
a&normalities and generally lac4
neuronal storage defects
- >i/use involvement of !hite matter
leads to deterioration in motor s4ills
spasticity hypotonia or ata"ia
- =ost are autosomal recessive
disorders5 adrenoleukodystrophy!
an O-lin4ed disease is a nota&le
e"ception
)itochondrial
encephalomyopathies
- are a group of disorders of
oidative phosphorylation! usually
resulting from mutations in the
mitochondrial genome+
- They typically involve gray matter as
!ell as s4eletal muscle
-
N18R/NA3 ST/RA,1 4*S1AS1S
Neuronal Ceroid 3ipofuscinoses
- set of inherited lysosomal storage
diseases that are grouped &ecause
they share the accumulation of
lipofuscinHan autofuorescent
su&stance !ith a variety of
ultrastructural appearancesHin
neurons.
- Neuronal dysfunction typically leads to
a com&ination of blindness! mental
and motor deterioration! and
sei'ures+
- These disorders are classi+ed based
on age of onset into infantile (:NC-)
late infantile (-:NC-) .uvenile (INC-)
and adult neuronal ceroid
lipofuscinoses (,NC-5 Puf disease) or
on the pattern of inclusions &y
electron microscopy+
Tay-Sachs 4isease
- disease &egins in early infancy !ith
developmental delay follo!ed &y
paralysis and loss of neurologic
function and death after several years
LEUKODYSTROPHIES
;rabbe 4isease
- an autosomal recessive
leu4odystrophy resulting from a
de(ciency of galactocere#roside
G-galactosidase
"galactosylceramidase$ - the
en3yme re<uired for the cata&olism of
galactocere&roside to ceramide and
galactose+
- clinical symptoms are dominated &y
motor signs including sti/ness and
!ea4ness !ith gradually !orsening
diNculties in feeding
%etachromatic 3eukodystrophy
- transmitted in an autosomal recessive
pattern and results from a de+ciency
of the lysosomal enzyme
arylsulfatase A.
- %n3yme de2ciency leads to an
accumulation of the sulfatides!
especially cere&roside sulfate
- most stri4ing histologic 2nding is
demyelination !ith resulting gliosis
Adrenoleukodystrophy
- is a progressive disease !ith
symptoms refera&le to myelin loss
from the CNS and peripheral
nerves as !ell as adrenal
insuKciency.
- The disease is associated #ith
mutations in the A*, gene on
chromosome O<(B !hich encodes a
mem&er of the ,T@-&inding cassette
transporter family of proteins ,CC>'+
(eli'aeus-%er'bacher 4isease
- an O-lin4ed invaria&ly fatal
leu4odystrophy &eginning either in
early childhood or .ust after &irth
- characteri3ed &y slo!ly progressive
signs and symptoms resulting from
#idespread #hite-matter
dysfunction.
- ,/ected individuals present !ith
pendular eye movements!
hypotonia! choreoathetosis! and
pyramidal signs early in the disease
follo!ed later &y spasticity!
dementia! and ataia+
Canavan 4isease
- characteri3ed &y megalocephaly!
severe mental de2cits &lindness and
signs and symptoms of !hite matter
in.ury &eginning in early infancy and
relentlessly progressing to death
!ithin a fe! years of onset
Aleander 4isease
- is characteri3ed &y megalencephaly!
sei'ures! and progressive
psychomotor retardation+
- There is #hite-matter loss typically
!ith a frontal-to-occipital gradient+
- The characteristic pathologic 2nding is
the euberant accumulation of
Rosenthal +bers around &lood
vessels in the su&pial and
su&ependymal 3ones and in the &rain
parenchyma
&anishing-.hite-%atter 3eukodystrophy
- characteristic progression of the
disorder as revealed &y imaging
studies is associated !ith mutations
in the genes encoding any of the
+ve subunits of eukaryotic
initiation factor A2 (e:7(C)+
%*T/C6/N4R*A3 1NC1(6A3/%7/(AT6*1S
)itochondrial encephalomyopathy%
lactic acidosis% and stro.eli.e episodes
"%13AS$
- most common neurologic syndrome
caused &y mitochondrial a&normalities
- characteri3ed &y recurrent episodes of
acute neurologic dysfunction
cognitive changes and evidence of
muscle involvement !ith !ea4ness
and lactic acidosis
%yoclonic 1pilepsy and Ragged Red
-ibers
- (=%RR7) is a maternally transmitted
disease in !hich a/ected individuals
have myoclonus! a sei3ure disorder
and evidence of a myopathy
3eigh Syndrome "Subacute Necroti'ing
1ncephalopathy$
- characteri3ed &y lactic acidemia
arrest of psychomotor development
feeding pro&lems sei3ures e"tra-
ocular palsies and !ea4ness !ith
hypotonia
;earn-Sayre Syndrome
- is a sporadic disorder most often
associated !ith a large mitochondrial
>N, deletion*rearrangement+
- The disorder presents !ith cere&ellar
ata"ia progressive e"ternal
ophthalmoplegia pigmentary
retinopathy and cardiac conduction
defects
Alpers 4isease
- This disorder com&ines neurologic
symptoms #ith evidence of
hepatic dysfunction and pathologic
2ndings including hepatitis and bile
duct proliferation+
To"ic and ,c<uired =eta&olic >iseases
&*TA%*N 41-*C*1NC*1S
Thiamine "&itamin 29$ 4e+ciency
- #eri#eri !hich is associated !ith
cardiac failure
- related to chronic alcoholism
- -ernic.e encephalopathy-
development of psychotic symptoms
or ophthalmoplegia that &egin
a&ruptly
- &orsa.o9 syndrome a prolonged
and largely irreversi&le condition
!hich characteri3ed clinically &y
memory distur&ances and
confa&ulation
- -ernic.e-&orsa.o9 syndrome D
com&ination
&itamin 29A 4e+ciency
- often causes anemia
- itially !ith num&ness tingling and
slight ata"ia in the lo!er e"tremities
&ut may progress rapidly to include
spastic !ea4ness of the lo!er
e"tremities
N18R/3/,*C S1L813A1 /- %1TA2/3*C
4*ST8R2ANC1S
6ypoglycemia
- Jlucose deprivation initially leads to
selective in.ury to large pyramidal
neurons of the cere&ral corte" !hich
if severe may result in pseudolaminar
necrosis of the corte" predominantly
involving deep layers
- #ippocampus and @ur4in.e cells are
also sensitive to hypoglycemia
6yperglycemia
- most commonly found in the setting of
inade<uately controlled dia&etes
mellitus and can &e associated !ith
either 4etoacidosis or hyperosmolar
coma
T/I*C 4*S/R41RS
Carbon %onoide
- result of hypo"ia from altered o"ygen-
carrying capacity of hemoglo&in
- Selective injury of the neurons of
layers *** and & of the cere&ral
corte" Sommer sector of the
hippocampus and (urkinje cells is
characteristic+
%ethanol
- preferentially a/ects the retina !here
degeneration of retinal ganglion cells
may cause &lindness
- -ormate a ma.or meta&olite of
methanol may have a role in the
retinal to"icity
1thanol
- ,cute ethanol into"ication are
reversi&le
- histologic changes are atrophy and
loss of granule cells predominantly
in the anterior vermis
Radiation
- e"posure to very high doses of
radiation "M9BBB rems$ can cause
intracta&le nausea confusion
convulsions and rapid onset of coma
follo!ed &y death
- The typical lesion is restricted to !hite
matter
Combined %ethotreate and Radiation-
*nduced *njury
- commonly develops !hen the drug
has &een administered in association
!ith radiation therapy either together
or at separate times
- pathologic &asis of the symptoms are
focal areas of coagulative necrosis
!ithin !hite matter
- Surrounding a"ons are often dilated
and form a"onal spheroids
- ad.acent gliosis of a"ons

DANE