Download Disease Description Group/Types Cause/Mutations Info/Clinical

Disease
Spina Bifida Occulta
Description
Asymptomatic bony defect or
severe malformation with a flat,
disorganized segment of the
spinal cord with meningneal
outpouching.
Group/Types
Neural Tube
defect
(Diagnosed
based on
imaging and
screening of
maternal blood
for afetoprotein)
Neural Tube
defect
Cause/Mutations
Anencephaly
Malformation of the anterior
end of the neural tube with
absence of the brain and
calvarium.
Megalencephaly
Volume of the brain abnormally
large
Forebrain
anomalies
Microencephaly
Volume of brain abnormally
small
Forebrain
anomalies
Lissencephaly
(agyria)
Decrease in the number of gyri
to total absence leaving a
smooth-surfaced brain
Forebrain
anomalies
-Gene encoding
microtubule-associated
protein LIS-1
-can also be caused by
enzymes responsible for
glycosylation of adystroglycan
Polymicrogyria
Small, unusually numerous and
irregular formed cerebral
convolutions. This also has
entraptment of apparent
meningeal tissue at point of
fusion that should be cortical
surface.
Forebrain
anomalies
-Induced by localized
tissue injury towards the
end of neuronal migration
-Also genetic forms
Info/Clinical symptoms
- Myelomeningocele
(meningomyelocele) = extension of the
CNS tissue through the defect 
mostly in lumbar with clinical defects
to motor and sensory in LE with
abnormal bowel and bladder control.
- Meningiocele = only meninges
extrude
Forebrain development is disrupted at
28 days  just area cerebrovasculosa
(flat remnant of brain tissue with
admized ependyma, choroid plexus
and meningothelial cells)
Occurs in chromosome abnormalities,
fetal alcohol syndrome and HIV-1
acquired inutero
- LIS-1 = complexes with dynein and
affects the function of the centrosome
in nuclear movement.
Disease
Neuronal
Heterotopias
Description
Migrational disorders where
neurons are in inappropriate
locations and are associated
with epilepsy
Heterotopia in the ventricular
system
Group/Types
Forebrain
anomalies
Cause/Mutations
Forebrain
anomalies –
Neuronal
heterotopias
Holoprosencephaly
Incomplete separation of the
cerebral hemisphere across the
midline
Forebrain
anomalies
Mutation in gene encoding
filamin A (an acting
binding protein 
assembly of the complex
meshworks of filaments)
Associated with trisomy
13 and other genetic
syndromes
Agenesis of the
corpus callosum
Absence of the white matter
bundles that carry cortical
projections from one
hemisphere to the other
Forebrain
anomalies
Dandy-Walker
malformation
Enlarged posterior fossa
-cerebellar vermis is absent or
present in rudimentary -form
in its anterior portion  in its
place is large midline cyst lined
by ependyma and is contiguous
with leptomeninges
Small posterior fossa,
misshapen midline cerebellum
with downward extension of
vermis through the foramen
magnum
-hydrocephalus
-lumbar myelo-meningocele
Discontinuous multisegmental
or confluent expansion of the
ependyma-lined central canal
Posterior fossa
anomalies
Periventricular
Heterotopias
Arnold-Chiari
Malformation (type
2)
Hydromyelia
Posterior fossa
anomalies
Info/Clinical symptoms
One location is in ventricular system =
Periventricular heterotopias.
-severe form  cyclopia
-less severe (arrhinenceophaly) 
absence of olfactory CN
-severity lowest to highest: normal 
lobar  semilobar  alobar
-radiological: misshapen lateral
ventricle (“bat-wing” deformity)
-associated with mental retardation or
can occur in clinically normal
individuals.
-cyst in this dz represents expanded,
roofless 4th ventricle in the absence of
the normally vermis
-Chiari malformation (type 1) = lowlying cerebellar tonsils extend down
into the vertebral canal
Disease
Description
Syngromyelia, syrinx Formation of fluid-filled
cleftlike cavity in the inner
portion of the cord
Syringobulbia
Formation of fluid-filled
cleftlike cavity in the inner
portion of the cord that may
extend into the brainstem
Ataxia Telangectasia
Ataxicdyskinetic syndrome in
early childhood 
development of telangiectasia
(dilated blood vessels in outer
layer of skin) in conjunctive
and skin
-immunodeficiency
Group/Types
Cause/Mutations
Info/Clinical symptoms
-Associated with the Chairi I and with
intraspinal tumors or following
traumatic injury
-disease occurs in 2nd-3rd decade of life
-symptoms: isolated loss of pain and
temp in UE (due to crossing anterior
spinal commissural fibers of the spinal
cord)
Autosomal recessive
-ataxia-telangiectasia
mutated (ATM) gene on
chromosome 11 (encodes
kinase needed for cell
response to ds DNA
breaks)
-show increase sensitivity to x-ray
induced chromosome abnormalities
-abnormalities are predominately
cerebellum with loss of Purkinje and
granule cells.
-Degeneration of dorsal columns,
spinocerebellar tracts, anterior horn
cells and peripheral neuropathy.
-telangiectatic lesions are in CNS,
conjunctive and skin of face, neck and
arms.
-disease is progressive and death early
in life.
-patients have recurrent
sinopulmonary infections and
unsteady walk  later have speech
problems, dysarthric, eye movement
abnormalities
-many develop lymphoid neoplasm, T
cell leukemia
Disease
Sturge-Weber
syndrome
Description
Venous angiomatous masses in
the cortical leptomeninges and
ipsilateral facial port wine nevi
Tuberous Sclerosis
in CNS
Tuberous Sclerosis
with NON-CNS
lesions
Group/Types
Cause/Mutations
Info/Clinical symptoms
-mental retardation, seizures,
hemiplegia and skull radio-opacities
-(large facial vascular malformation in
child with mental deficiency may
indicate a extensive vascular
malformations)
Development of hamartomas
and benign neoplasms
Autosomal dominant
-locus TSC1 on
chromosome 9 (encodes
protein hamartin) or locus
TSC2 at chromosome 16
(encodes tuberin)  these
inhibit kinase mTOR that
regulates protein
synthesis and other
anabolic metabolisms.
-Hamartomas in CNS = cortical tubers
and subependymal nodules
-subependymal giant-cell
astrocytomas (low grade neoplasms
that develop from hamartomatous
nodules)
-cortical tubers are epileptogenic and
sx beneficial
Development of hamartomas
and benign neoplasm’s
Autosomal dominant
-mutations same as above.
-renal angiomyolipomas, retinal glial
hamartomas, pulmonary
lymphangioleiomyomatosis and
cardiac rhabdomyomas
-cysts can be found in liver, kidneys
and pancreas
-cutaneous lesions  angiofibromas,
localized leathery thickenings
(shagreen patches), hypopigmented
(Ash-lead patches) and subungual
fibromas
Disease
Tay Sachs
Description
-Mutation leads to deficiency of
hexosaminidase A (which
breaksdown GM2)
-Inability to catabolize GM2
ganglioside leading to
accumulation of GM2
ganglioside
-symptoms = motor
coordination, mental
obtundation  muscle
flaccidity, blindness and
increasing dementia
Group/Types
GM2
Ganliosideosis
Hexosaminidase
a-subunit
deficiency
Cause/Mutations
Mutation in a-subunit
locus of chromosome 15
Info/Clinical symptoms
-prevelent among Ashkenazic Jews
-Gangliosides mostly accumulate in
neurons in CNS, ANS and retina
-neurons are ballooned with
cytoplasmic vacuoles
-stains oil red O and sudan black are
positive
-infants normal at birth but show
symptoms at 6 months vegetative at
1-2 yrs and dead at age 2-3 y/o
-cherry-red spot in macula of the eye
-Clinically similar diseases: sandhoff
(due to B-subunit defect) and GM2
activator deficiency
Niemann-Pick
disease Type A and
B
-Sphingomyelinase deficiency
(which is required for cell
membranes) so deficiency
blocks degredation of the lipid
resulting in accumulation of
sphingomyelin in lysosome
mainly in cells in
mononuclear phagocyte system
Sphingomyelina
se deficiency
Missense mutation to
chromosome 11 p15.4
Type A: Almost complete
deficiency of
sphingomyelinase
-Common in Ashkenazi Jews
-Enlarged cells (90um) filled with
sphingomyelin and cholesterol have a
foaminess to the cytoplasm
-Foam cells found in: spleen, liver,
lymph nodes, bone marrow, tonsils, GI
and lungs
-Clinical symptoms:
hepatosplenomegaly, brain gyri are
shrunken and sulci, diffuse neuronal
involvement, vacuolation and
ballooning of neurons  cell death and
loss of brain substance, retinal cherryred spot
-Type A: also have protuberant
abdomen, progressive failure to thrive,
vomiting, fever, generalized
lymphadenopathy, decrease
psychomotor skills.
Severe infant
form with Type
A: neurological
involvement due
to visceral
accumulations
of
sphingomyelin
Apparent
by 6 mo, death
at 1-2 y/o
-Type B:
patients have
organomegaly
but NO CNS
involvement
Disease
Gauchers disease
Description
Glucocerebroside accumulates
in phagocytes or sometimes
CNS.
-Not only do they store more
glucocerebrosides but
macrophages are activated
secreting cytokines: IL-1, IL-6
and TNF
Chronic non-neuronopathic
form  glucocerebrosides
limited to mononuclear
phagocytes without brain
involvement
Group/Types
There are 3
types (each
listed below)
Cause/Mutations
Autosomal Recessive
-Mutation in gene for
glucocerebrosidase (which
cleaves glucose residues
from ceramide)
Info/Clinical symptoms
-distended phagocyte cells = called
Gaucher cells around found in: spleen,
liver, bone marrow, lymph nodes,
tonsils, thymus, Peyer’s patch.
-Gauchers cells have fibrillary type of
cytoplasm (look like crumpled tissue
paper
Gauchers
Disease (see
more details
above)
-Type 1: reduced but +
levels of glucocerebroside
activity
Gauchers Type 2:
Acute neuronopathic Gauchers
 infantile acute cerebral
pattern
Gauchers
Disease (see
more details
above)
NO detectable
gluocerebroside activity in
tissues
-Common in Jews of European stock
-Longevity is shortened and
progressive in adults but is compatible
with a long life
-First appear in adult
-Clinical symptoms: splenomegaly or
bone involvement (splenic and
skeletal) pancytopenia or
thrombocytopenia due to
hypersplenism, pathological fractures
and bone pain due to expansion of
marrow space
No predilection for Jews
-heptaosplenomegaly present but
progressive CNS involvement is
dominant leading to death at an early
age.
-Clinical symptoms: CNS
abnormalities, convulsions,
progressive mental deterioration, and
affects organs such as: liver, spleen
and lymph nodes
Gauchers Type 3:
Intermediate between Type 1 &
2
Gauchers
Disease (see
more details
above)
Systemic involvement
Gauchers Type 1:
Progressive CNS disease beginning in
adolescence or early adulthood
-Clinical symptoms: same as type 2:
Disease
Mucopolysaccharido
ses (MPS)
Description
Accumulation of
mucopolysaccharide are in
mononuclear phagocytic cells,
endothelial cells, intimal
smooth muscle cells and
fibroblast throughout the body.
Group/Types
There are types
1-7, each with a
specific enzyme
deficiency (so
clinical picture is
different for
each type)
Cause/Mutations
Deficiency of lysosomal
enzymes fro the
degredation of
mucopolysaccharides
(glycosaminoglycans)
which are long chain
complex carbs linked to
form proteoglycans (in
connective tissues)
-All are autosomal
recessive (except Hunters
syndrome = X-linked
recessive)
Info/Clinical symptoms
-The glycosaminoglycans that
accumulate in MSP are: dermatan
sulfate, heparan sulfate, keratan
sulfate, and chondroitin sulfate
-The enzyme that degrade MPS cleave
the terminal sugar from the
polysaccharide chain diposed along a
polypeptide or core protein
-Common sites involved: spleen, liver,
bone marrow, lymph nodes, blood
vessels, and heart.
-Clinical symptoms:
hepatosplenomegaly, skeletal
deformities, valvular lesions,
subendothelial arterials (mainly in
coronary arteries and the brain)
 can lead to coronary subendothelial
lesion  MI
-Cardiac decompensation and MI are
main causes of death
Hurler syndrome
MPS 1-H
Type 1:
Deficiency of a-IMucopolysaccari iduronidase
doses (MPS
deficiency)
-One of the most severe forms of MPS
-normal at birth  develop
heptosplenomegaly by age 6-24 y/o
-Other clinical symptoms: growth
retardation, coarse facial features,
skeletal deformities
-death occurs by age 6-10y/o mostly
due to cardiovascular complications
Hunter Syndrome
MPS 2
Mucopolysaccari X-linked inheritance
doses (MPS
deficiency)
Clinical symptoms: absence of corneal
clouding and milder symptoms
Disease
Neuronal Ceroid
Lipofuscinoses
Description
Accumulation of lipofuscin
(autofluorescent substance
with a variety of ultrastructural
appearance in neurons)
Group/Types
Neuronal
Storage Disease
Cause/Mutations
Inherited lysosomal
storage disease
Info/Clinical symptoms
Clinical symptoms: blindness, mental
and motor deterioration, seizure
-Classified by age of onset:
 infantile (INCL), late infantile
(LINCL), juvenile (JNCL) and adult
neuronal ceroid lipofuscinoses (ANCL;
Kuf disease)
-Also can be classified by pattern of
inclusions by electron microscopy
Krabbe Disease
Deficiency of
galactosylceramidase is needed
for catabolism of
galactocerebroside  cermaide
and galactose
(accumulation of
galactocerebroside is NOT the
direct toxic agent)
-The alternate catabolic
pathway removes the fatty acid
from this molecule making
galactosylsphingosine which IS
cytotoxic causing
oligodendrocyte injury
Leukodystrophi
es
Autosomal recessive
disease with deficiency of
galactocerebroside Bgalactosidase
(galactosylceramidase)
-chromosome 14q31
-Clinical symptoms are dominated by
motor signs: stiffness, weakness, with
gradual worsening difficulties in
feeding
-Clinical course is rapidly progressing
with onset between 2-6 mo
-usually causes death prior to 2 y/o
Metachromatic
Leukodystrophy
Arylsulfatase A which cleaves
the sulfate from the sulfatecontaining lipid (sulfatide) in
their degredation  deficiency
causes accumulation of
sulfatides
(especially cerebroside sulfate)
Leukodystrophi
es
Autosomal recessive with
deficiency of lysosomal
enzyme: arylsulfatase A
-Chromosome 22q
-Clinical subtypes include: late
infantile form (most common),
juvenile form and adult form
-Symptoms Child onset: motor
symptoms which progress gradually
with death in 5-10 yrs
 Adult form: initial symptoms are
psychiatric or cognitive symptoms
with motor symptoms coming later
Disease
Adrenoleukodystrop
hy
Description
Progressive disease with
myelin loss from the CNS,
peripheral nerves and adrenal
insufficiency
Group/Types
Cause/Mutations
-X-linked form: earliest
onset
-Mutation of the ALD gene
on chromosome Xq28
(which encodes the ATP
binding cassette
transporter family of
proteins ABCD1)
Info/Clinical symptoms
Earlier onset have more rapid course:
X-linked  presents in school years
with neuro symptoms and adrenal
insufficiency and rapidly progressive
 fatal
-later onset in adults: slowly
progressing with PNS involvement
developing over decades
-There will be loss of myelin, gliosis
and lymphocytic infiltration with
atrophy of the adrenal cortex
-inability to properly catabolize
very-long-chain fatty acids
(VLCFA) in peroxisomes with
elevated VLCFA in serum
-Mitochondrial
Encephalomyopathy
-Lactic Acidosis,
-Strokelike episodes
(MELAS)
-These are common
neurological syndromes
-Characterized by recurrent
episodes of acute neurological
dysfunction, cognitive changes,
muscle involvement with
weakness and lactic acidosis
Mitochondrial
Encephalomyop
athies
-Mutation for MELAS:
tRNA
-Coding-gene mutations
have also been seen
-Most present as a muscle disease
while second most common is CNS
-Pathologically areas of infarction are
seen with vascular proliferation and
focal calcification
Myoclonic epilepsy
and ragged red
fibers (MERRF)
Syndrome that causes
myoclonus (a seizue disorder)
and evidence of myopathy
Mitochondrial
Encephalomyop
haties
Maternally transmitted
disease
-Also associated with
tRNA mutation
-Can also see ataxia due to neuronal
loss of cerebellar system (inferior olive
in medulla, cerebellar cortex and deep
nuclei)
Leigh Syndrome
(Subacute
Necortizing
Encephalpathy)
Syndrome that causes lactic
academia, arrest of
psychomotor development,
feeding problems, seizures,
extra-ocular palsies and
weakness with hypotonia
Mitochondrial
Encephalomyop
haties
Diverse mutations
affecting mitochondrial
genome-encoded
components of oxidative
phosphorylation
complexes
-Also possibly
mitochondrial tRNA
mutations
-Usually in early childhood
-Death occurs within 1-2 yrs
Disease
Thiamine (Vit B1)
deficiency
Description
-Can be associated with
Beriberi and its associated
cardiac failure
Group/Types
Acquired
Metabolic
Disease
Usually called
WernickeKorsakoff
syndrome
Vitamin B12
deficiency
Causes anemia and potential
irreversible effects on the
nervous system
Acquired
Metabolic
Disease
Hypoglycemia
Initially leads to selective injury
to large pyramidal neurons of
the cerebral cortex
-If severe: result in
pseudolaminar necrosis of the
cortex
Neurological
Sequelae of
Metabolic
Disturbances
Cause/Mutations
Info/Clinical symptoms
-Can lead to the development of
psychotic symptoms or
ophtalmoplegia  Wernicke
encephalopathy (but treatment with
thiamine can reverse symptoms)
-Acute stages due to prolonged,
untreated deficiency may lead to 
Korsakoff syndrome memory
disturbances and confabulation
-Common in chronic alcoholism or
individuals with gastric disorders like
carcinomas, chronic gastritis or
persistent vomiting
-Neuro symptoms that occur within a
few weeks = numbess, tingling and
slight ataxia in LE but progress rapidly
to spastic weakness in LE
-Vitamin replacement can cause
clinical improvement
If complete paralegia occurs later in
disease, recover is poor
-Similar to O2 deprivation
-Some areas of the brain more
sensitive to hypoglycemia  if severe
enough can lead to widespread brain
injury
-Hippocampus is vulnerable showing
loss of pyramidal neurons in Sommer
sector (area CA1)
-Purkinje cells of the cerebellum are
sensitive but to lesser extent then
hypoxia
Disease
Hyperglycemia
Description
Inadequately controlled
diabetes mellitus and can be
associated with ketoacidosis
and hyperosmolar coma
Group/Types
Neurological
Sequelae of
Metabolic
Disturbances
Carbon Monoxide
Hypoxia from O2-carrying
capacity of hemoglobin
Toxic disorders
Methanol
Affects the retina where
degeneration of retinal ganglia
cause blindess
Chronic alcohol abuse:
neurological sequelae including
Wernicke-Korsakoff syndrome
Toxic disorders
Ethanol
Toxic disorder
Cause/Mutations
Info/Clinical symptoms
-Clinical symptoms: dehydration,
development of confusion, stupor and
eventual coma
-fluid depletion must be corrected
gradually or else severe cerebral
edema will arise
-Severe injury of neurons of layers 3 &
4 of cerebral cortex, sommer sector of
hippocampus and Purkinje cells
-Bilateral necrosis of the globus
pallidus
-Bilateral putamenal necrosis and focal
white matter necrosis occur if
exposure is severe
-either due to direct or secondary
nutritional deficits
-cerebellar dysfunction can occur (1%
chronic alcoholics)  associated with
clinical syndrome of truncal ataxia,
unsteady gait and nystagmus
Disease
Tay-Sach’s Disease
Description
Inability to Catabolize GM2
Gangliosidosis
Deficinecy of hexosaminidase A
Neurons are ballooned with
cytoplasmic vacuoles
Common among jewish
population
Mutation
α-Subunit locus on chromosome 15
Sandhoff Disease
GM2 Activator deficiency
Neimann-Pick Disease
GM2 Gangliosidosis
GM2 Gangliosidosis
Lysosomal accumulation of
sphingomyelin due to an
inherited deficiency of
spingomyelinase
Β-subunit defect
Type A NPD: Severe infantile
form with neurologic
involvement, visceral
accumulations of
sphingomyelin, and progressive
wasting and early death .
Type B NPD: Pts have
ortanomegaly but not CNS
involvement. Can survive into
adulthood
Type A: Missense mutation resulating in
almost complete deficiency of
sphingomyelinase.
Chromosome 11p15.4
More than 100 mutations with a
correlation between type of mutation and
severity
Clinical
Accumulation of GM2 Gangliosidosis
affects neurons in the CNS, ANS, and
retina
Normal at birth symptoms begin
around 6months motor and
mental deterioration including
motor incoordination, blindness,
muscular flaccidity
Cherry red spot in macula
Similar to clinical features of TaySach’s listed above
Affected cells become enlarged with
innumerable small vacuoles of
uniform size are created giving
cytoplasm a “foaminess” look. These
cells are found in spleen, liver,
lymph nodes, bone marrow, tonsils,
GI and lungs.
Brain gyri are shrunken and sulci
widened. This effects are diffuse.
Vacuolation and ballooning of
neurons constitute histological
change. Rtinal cherry-red spot is
also occasionally present
Type A: Symptoms may be present
at birth to 6months. Infants have
protuberant abdomen, which is
followed by failure to thrive,
vomiting, fever, lymphadenopathy.
Death within1-2 years.
Disease
Description
Mutation
Gaucher Disease
Accumulation of
glucocerebrosides activating
Mac, IL-1, IL-6, and TNF.
Distended phagocytic cells 
Gaucher cells
Type 1: Chronic nonneuronopathic form.
Glucocerebrosides accumulate
in mononuclear phagocytes. NO
BRAIN INVOLVEMENT!
Type 2: Acute neuropathic.
Infantile acute cerebral pattern.
No detectible
glucocerebrosides.
Type 3: intermediate between I
and II
Autosomal recessive disorder- mutation
in gene encoding glucocerebrosidase
Have types I-VII each resulting
form the deficiency of one
specific enzyme
Accumulation of MPS are
foundin mononuclear
phagocytic cells, endothelial
cells, intimal smooth muscle
cells, and fibroblasts
Hurler Syndrome: MPS 1-H.
Deficiency of α-I-iduronidase.
Severe form. Affects children
6-24 months
Hunter syndrome: MPS II
Autosomal X-linked
Genetically determined deficiency of
lysosomal enzymes involved in
degradation of MPS
Most autosomal recessive except Hunter
syndrome
Description
Mutation
Mucoploysachharideoses
(MPS)
Disease
Clinical
Type 1: Splenic and skeletal
involvement dominate. Longevity
not markedly decreased . Symptoms
appear in adult life
Type 2: Hepatospelnomegaly.
Progressive CNS involvement.
Convulsions and progressive mental
deterioration. Death at an early age
Type 3: Systemic involvement but
no progressive CNS disease. Usually
begins in adolescence or early
adulthood.
Hepatosplenomegaly, skeletal
deformities, valvular lesions, and
subendothelial arterial deposits
Hurler Syndrome: Growth is
retarded, coarse facial features, and
skeletal deformities. Death by 6-10
due to cardiovascular problems
Hunter Syndrome: absence of
corneal clouding. Milder clinically
Clinical
Schwannoma
Benign tumor arises form
neural crest derived Schwann
cells. Common component of
Neurofibromatosis 2
Well circumscribed,
ecapsulated, easily separated
form nerve
Neurofibroma
Present as discrete localized
masses. Most commonly
cutaneous or in a peripheral
nerve as solitary neurofibroma
The presence of multiple of
plexiform neurofirboma suggest
diagnosis of neurofibromatosis
type 1 (NF1)
Plexiform Neurofibroma: result
in significant neurologic deficit.
Difficult to remove and
significant potential for
malignant transformation
Malignant Peripheral
Nerve Sheath Tumor
Disease
Highly malignant that are locally
invasive, frequently recurrent
and spread. Commonly in
medium or large nerves 50%
arise from plexiform
neurofibroma or radiation
Description
Inactivatin mutation in NF2 gene on
chromosome 22. Resulting in the loss of
merlin product Cells then
hyperproliferate because merlin is no
present to restrict expression of GFR
Compression of involved nerve or
adjacent structures. Commonly
cerebellopontine angle presenting
with tinnitus and hearing loss
(acoustic neuroma, CN 8)
Histologically: Antoni A- elongated
cells with cytoplasmic processed
arranged in fascicles. Verocay
bodies are the “nuclear free zones”
Antoni B timor is less densely
cellular consisting of loose
meshwork of cells
Skin lesions grow nodules
sometimes overlying
hyperpigmentation. Mostly
cosmetic very little risk of these
becoming malignant.
Alteration in both copies of NF1 gene
have been observed in Schwann cell
component of plexifrom neurofribromas
supporting critical role for loss of NF1
function which is to produce
neurofirbomin that stimulate GTPase that
inhibits RAS
May arise anywhere along a nerve.
Affected nerves are irregularly
expanded as each fascicle is
infiltrated by neoplasm. No possible
to separate lesion from nerve.
Lesion is loose, myxoid background
with low cellularity. Schwann cells,
multipolar fibroblastic ells,
inflammatory cells, and axons are all
present in tumor
NF1 function is lost and subsequent
alteration often disrupt p-53 and Rbdependent pathways for regulating cell
proliferation
Mutation
Clinical
Neurofibromatoses (Von
Recklinghausen Disease)
Neurofibroma, gliomas or optic
nerve, pigmented nodules of iris
(Lisch nodules) and cutaneous
hyperpigmented macules (café
au lait spots)
Autosomal dominant
Type 1 (NF1): Proprensity for
plexiform neurofibromas to
undergo malignant
degeneration at higher rate than
comparable tumors
Type 1: Course is highly variable
some have no symptoms other
develop progressive disseae with
spinal deformities, disfiguring
lesions, and compression of vital
structures.
Type 2 (NF2): Range of tumors
commonly bilateral eight nerve
schwannomas and multiple
meningiomas. Non neoplastic
lesions including nodular
ingrowth of Schwann cells to
spinal cord,
meningioangiomatosis and glial
harmartia
Disease/ Injury
Description
MOI
Symptoms
Diastic Skull fracture
Kinetic energy from fracture
dissipated to fused suture. This
type is when it crosses the
suture
Displaced Skull fracture
The bone is displaced into
cranial cavity by distance
greater than bone thickness
Linear Skull fracture
Branching fracture radiating out Fall and hit head on hard surface
from main fracture line
Majority are this type!
Basilar skull fracture
Fracture of the base of the skill
Follows impact to occiput or side of head
(MVA)
Symptoms can be referred to lower
cranial nerves or cervicomedullary
region, presence of orbital or
mastoid hematomas can also be
present. CSF may discharge from
nose or ear.
Ring Fracture
Fracture that encircles or nearly
encircles the foramen magnum
Concussion
Clinical syndrome of altered
consciousness
Head forcibly pushed inferiorly into
vertebral column or visa versa
EX: someone jump from great high and
land on feet
Head injury brought on by change in
momentum
Contusion
DIRECT PARENCHYMAL
INJURY
Blow to surface of brain leading
to rapid tissue displacement,
disruption of vascular channels,
hemorrhage, and edema
(Crest of gyri most susceptible)
Getting hit in head with hammer
Instant onset of transiet
neurological dysfunction, LOC, loss
of reflexes, temporary respiratory
arrest
Typically happens when head is mobile at Coup Injury: Develops a contusion
time of injury
at point of contact
Countrecoup Injury: Contusion on
brain surface diametrically
opposite to point of contact
Usually after sudden deceleration
Disease/ Injury
Diffuse Axonal Injury
Description
Axonal swelling. Mechanical
force assoc with trauma
damage integrity of axon at
node of Ranvier
Wearing of an artery
extravasation of blood under
arterial pressure can cause dura
to separate from inner surface
of skull
MOI
Angular acceleration (even in absence of
impact) or hemorrhage
Symptoms
Injury greatest where density
difference is greatest. Many indv.
w/ coma have this injury
Injury to dural arteries most commonly
the middle meningeal artery. Commonly
injured in temporal skull fractures
Expanding hematoma compress
brain and can expand rapidly—
emergency requiring drainage
Subdural Hematoma
Between inner surface of dura
and outer arachnoid layer
Bridging veins traveling from cerebrum
though dura and arachnoid to empty into
sinus can be torn @ point where they
penetrate dura during trauma
Usually manifest within 48hours
of injury normally over lateral
aspects of brain. Non-localizing
headaches and confusion are
common along with slowly
progressing deterioration.
Common in elderly patients even
with mild trauma
Gunshot Wound
Entrance Wound: Usually round with associated marginal abrasion
Exit Wounds: Typically tear skin and have irregular margins
Contact Gunshot Wound: Associated with muzzle stamp or soot
Close Range: Soot and searing of skin
Medium Range: Some soot stippling around entrance wound
Distance Range: No gunpowder or other defect of the skin associated with entrance wound
Child Abuse
Child with head trauma
Post Traumatic
Hydrocephalus
Build up of CSF around brain
Epidural Hematoma
“Shaken baby syndrome”
Scalp contusions, subdural
hematoma or blood, perioptic
nerve or retinal hemorrhages
Due to obstruction of CSF resportion
from hemorrhage into subarachnoid
space
Post Traumatic Dementia
Follow repeated head trama during
and Punch drunk Syn
protracted period
Post Traumatic Epilepsy, tumors, infection, diseases, and psychiatric disorders can also follow head trauma
Disease/ Injury
Spinal Cord Trauma
Description
MOI
Segmental damage to descending and
ascending white matter isolates distal
cord from CNS connections
Symptoms
Above C4 Resp compromise
Cervical Lesions Quadriplegia
Thoracic and below Paraplegia
Vasogenic Edema
Increased CSF volume
Caused by BBB disruption and increased
vascular permeability allowing fluid to
shift form intravascular compartment to
intercellular space of brain
Can be localized or generalized
Cytotoxic Edema
Increased CSF volume
Interstitial Edema
(hydrocephalic edema)
Increased CSF volume
Increase in intracellular fluid 2ndary to
neuronal, glial, or endothelial cell
membrane injury
Increase in intravascular pressure causes
abnormal flow of fluid from
intraventricular CSF across ependymal
lining to periventricular white matter
Common in patients with
generalized hypoxic/ischemic
insult or with metabolic disease
Occurs especially around lateral
ventricle
Generalized Edema
Gyri are flattened, Sulci are
narrowed, and ventricular
cavities are compressed. As
brain expands herniation may
occur
Accumulation of excessive CSF
within ventricular system
increases volume of ventricles
and expands them increasing
intracranial pressure
Communicating: enlargement of
all ventricular sytem
Non –Com: Only portion of
ventricular system is enlarged
(usually mass in 3rd ventricle)
Impaired flow and resorption or
overproduction of CSF
Infancy Enlarged head
(increased circumference)
After Infancy Expansion of
ventricles and increased pressure
without change in head
circumference
Hydrocephalus
Hydrocephalus ex vacuo:
dilation of ventricular system
with ↑ in CSF volume 2ndary to
loss of brain parenchyme
Disease/ Injury
Description
MOI
Symptoms
Increased Intracranial
Pressure
Volume of brain increases
beyond limit permitted by
compression of veins and
displaced CSF
Associated with diffuse brian edema or
focal effect (Tumor, abscesses, or
hemorrages)
Can lead to herniation Syndrome
Subfalcine (cingulate): Unilateral
expansion of cerebral hemisphere
that displaces cingulate gyrus.
Compression branches of Ant.
Cerebral a.
Transtentorial: Medial aspect of
temporal lobe is compressed
against free margin of tentorium.
CN 3 compromised: pupillary
dilation and impaired ocular
movement (ipsilateral side).
Post Cerebral a. compressed:
ischemic injury, impairing visual
cortex.
Contralateral cerebral peduncle
may also be compressed resulting
in ipsilateral hemiparesis known as
Kernohan’s notch
Lesions to the midbrain and pons
are also commonly present and
termed secondary brainstem or
Duret hemorrhages
Tonsillar Herniation: Displacement
of cerebellar tonsills through
foramen magnum. Life threatening
because of compression placed on
brainstem and vital respiratory and
cardiac centers in medulla