vasogenic localized

Cerebral
edema
generalized
cytotoxic
 Cerebral edema
• Increased fluid leakage from blood vessels or injury to various cells of the
CNS

• Vasogenic edema-increase in extracellular fluid caused by BBB disruption

and increased vascular permeability, fluid shifts from intravascular
compartment to intercellular
• Types:
• Localized (adjacent to inflammation or neoplasms)
• Generalized(follows ischemic injury)

• Cytotoxic edema-increase in intracellular fluid secondary to neuronal, glial,

or endothelial cell membrane injury
• Causes: hypoxic/ischemic insult or with a metabolic derangement that
prevents maintenance of the normal membrane ionic gradient
• Generalized edema:
• gyri are flattened
• sulci are narrowed
• ventricular cavities are compressed
• As the brain expands, herniation may occur
• Complications:
• Macrocephaly-when develops in infancy before closure of the cranial sutures
• Increased ICP-when develops after 27 month
 Hydrocephalus types:
• Noncommunicating(obstructive)
• ventricular system is obstructed and does not communicate with the
subarachnoid space, as may occur because of a mass in the third ventricle
• Communicating
• ventricular system is in communication with the subarachnoid space, and
there is enlargement of the entire ventricular system
• Hydrocephalus ex vacuo
• compensatory increase in ventricular volume secondary brain parenchyma
loss
CSF pressure is transmitted to
the inner ear fluids (perilymph
and/or endolymph) via the
cochlear aqueduct and/or
endolymphatic sac, and that
these inner ear pressure
alterations can produce some
degree of hearing loss
 Herniation
• Displacement of brain tissue past rigid dural folds (the falx and
tentorium) or through openings in the skull because of increased
intracranial pressure
• Subfalcine (cingulate)
• unilateral or asymmetric expansion of a cerebral hemisphere displaces the
cingulate gyrus under the falx
• leads to compression of the anterior cerebral artery

• Tonsillar herniation
• displacement of the cerebellar tonsils through the foramen magnum
• brainstem compression and compromise od cardiorespiratory centers in
medulla(can be fatal)
• Transtentorial (uncinate, mesial temporal) herniation
• medial aspect of the temporal lobe is compressed against the
free margin of the tentorium

• 3d cranial nerve is compromised:

-pupillary dilation, impairment of ocular movements

• posterior cerebral artery may also be compressed

• Kernohan notch-contralateral cerebral peduncle may be

compressed, resulting in hemiparesis ipsilateral to the side of
the herniation

• Duret hemorrhages-Progression of transtentorial herniation is

often accompanied by secondary hemorrhagic lesions in the
midbrain and pons
Hydrocephalus
Urinary/bowel incontinence
Learning problems
Low skin sensation
Movement problems
Leg paralysis
 Anencephaly

Area cerebrovasculosa-forebrain remnant, flattened

disorganized brain tissue with admixed ependyma,
choroid plexus, and meningothelial cells.
Encephalocele
 Forebrain anomaly
• Megalencephaly/Microencephaly
• -chromosome abnormalities, fetal alcohol syndrome, HIV-1 acquired in utero
• Lissencephaly(agyria)
• type 1-smooth surfaced brain
• type 2-rough or cobblestoned surfaced brain

• Polymicrogyria
• small, unusually numerous, irregularly formed cerebral convolutions
• Neuronal heterotopias
• -neurons are present in inappropriate place, seizures are common
• Holoprosencephaly
• -incomplete separation of cerebral hemispheres, common in trisomy 13
• -manifests as cyclopia; arrhinencephaly(absence of olfactory nerves)

• Agenesis of the corpus callosum

• -Radiology: misshapen lateral ventricles (“bat-wing” deformity);
 Posterior Fossa
Anomalies
• Chiari type I malformation
• less severe
• low-lying cerebellar tonsils extend down into the vertebral canal
• may be a silent or may become symptomatic because of impaired CSF flow
and medullary compression
• Arnold-Chiari malformation (type II)
• small posterior fossa, a misshapen midline cerebellum
• downward extension of vermis through the foramen magnum
• hydrocephalus and a lumbar myelomeningocele

• associated changes:
• caudal displacement of the medulla
• malformation of the tectum
• Aqueductal stenosis
• cerebral heterotopias
• hydromyelia
• Dandy-Walker malformation
• Enlarged posterior fossa
• cerebellar vermis-absent or present only in rudimentary form
• Out of vermis, large midline cyst presents
• Cyst is lined by ependyma and is contiguous with leptomeninges
• Dysplasias of brainstem nuclei are common
• Joubert syndrome and its related disorders
• hypoplasia of the cerebellar vermis
• Elongation of the superior cerebellar peduncles
• Altered shape of the brainstem
• ‘molar tooth sign’ on imaging
• Hydromyelia-expansion of the ependyma-lined central canal of the cord
• Syringomyelia-formation of a fluid-filled cavity in spinal cord
• syringobulbia-when fluid extend into the brainstem

• Syringomyelia associations:
• Chiari malformations; intraspinal tumors

• Manifestation:
• In 2/3 decade
• isolated loss of pain and temperature sensation in the upper
extremities(caused by crossing anterior spinal commissural fibers of the
spinal cord)
• CP-nonprogressive neurologic motor deficit
• types: spasticity, dystonia, ataxia/athetosis, and paresis
 Diffuse axonal injury
• Defined clinically as a loss of consciousness lasting > 6
hours in the absence of a specific focal lesion.
• Edema from the injury often increases ICP, leading to
various manifestations
• DAI is underlying injury in shaken baby syndrome
 Basilar skull fracture

• Manifestations:
• CSF rhinorrhea
• CSF otorrhea
• Hemotympanum-blood behind the tympanic membrane
• Battle sign-ecchymosis behind the ear
• Raccoon eyes- in periorbital area
• Loss of smell/hearing
• Facial nerve function impairment
 GCS
• Quick , reproducible scoring system
• Initial examination to estimate TBI severity

• 14 or 15 is mild TBI
• 9 to 13 is moderate TBI
• 3 to 8 is severe TBI
 Caput succedaneum

• swelling, or edema, of an NB’s scalp soon after delivery

• caused by prolonged pressure from the dilated cervix or vaginal walls during
delivery
• Usually resolves spontaneously within a few days
 cephalhematoma
• hemorrhage in the plane between the bone and the periosteum on the
surface of the skull in a newborn
• increases in size after birth before resolving over a few weeks
• c. Dystrophic calcification may occur within the hematoma and may result in
a hard skull
• protuberance that may require months of skull growth and remodeling for
resolution.
• d. Most are unilateral and located over the parietal bone.
• e. Associated with forceps delivery and attributed to shearing forces that
separate the
• periosteum from the skull bone
 CVD

survival of the tissue depends on:

Ischemic-80%, late onset sympt.
- collateral circulation
Hemorrhagic-20%, sudden onset
- duration of ischemia
- magnitude and rapidity of the reduction of flow
Subdural hematoma

-venous bleeding is self-limited

-manifest within 48 hours of
injury
-bilateral in about 10%
 Subarachnoid Hemorrhage (SAH)

• Sudden bleeding into the subarachnoid space

• Causes: I(aneurysm), II(trauma)
• Less common causes:
• mycotic aneurysms, AV malformation, bleeding disor.
• Blood in the subarachnoid space causes a chemical
meningitis that commonly increases ICP
Xanthochromia

-Caused by oxyHb breakdown to Bilirubin

-first appears in 12 hours after a bleed and peaks in
2 to 4 days
-subsides in 2 to 4 weeks.
 Aneurysm causes:

• Mostly sporadic(smoking, HTN)

• Associated diseases:
• Autosomal dominant polycystic kidney disease
• Ehlers-Danlos syndrome type IV
• Neurofibromatosis type 1 [NF1]
• Marfan syndrome
• Fibromuscular dysplasia of extracranial arteries
Types:
• Rupture may occur at any time
• In 1/3 it is associated with acute increases in ICP(straining, orgasm)
• Between 25%-50% of patients die with the first rupture
Most common site of strokes
 Global cerebral ischemia
• Generalized reduction of cerebral perfusion (as in cardiac arrest, shock,
and severe hypotension)
transient post-
ischemic confusion
reversible

complete recovery

damage
widespread
neuronal
death
irreversible
persistent
vegetative
state
 Focal cerebral ischemia
• Follows reduction or cessation of blood flow to a localized area of the
brain due to arterial occlusion or hypoperfusion
• Causes:
• Emboli
• Inflammation: infectious, noninfectious
 Hypertensive Cerebrovascular Disease
• Lacunar infarcts
• Slit hemorrhages
• Hypertensive encephalopathy
• Massive hypertensive intracerebral hemorrhage
 Lacunar infarcts
• Arteriolar sclerosis of arteries supplying:
• basal ganglia, white matter, brainstem
• Leads to single/multiple, small, cavitary infarcts known as lacunes
• Lakelike spaces, less than 15 mm wide
• occur in:
• Lenticular/caudate nucleus, thalamus, internal capsule, deep white matter,
pons
• Microscopy: tissue loss surrounded by gliosis
• sometimes, widening of the perivascular spaces without infarction (état
criblé)
 Slit Hemorrhages
• HTN ruptures small caliber penetrating vessels, small hemorrhages develop
• When hemorrhages resorb, slitlike cavity (slit hemorrhage) surrounded by
brownish discoloration is left
• Microscopy:
• focal tissue destruction, pigment-laden macrophages, and gliosis
• Caused by malignant hypertension
• characterized by:
• Diffuse cerebral dysfunction- headaches, confusion, vomiting, and
convulsions, coma
• At postmortem: edematous brain with/without transtentorial or tonsillar
herniation
• Microscopically: Petechiae, fibrinoid necrosis of arterioles
• Binswanger disease(subcortical vascular dementia)
• When injury involves large areas of the subcortical white matter-myelin/axon
loss
 Intraparenchymal Hemorrhage(stroke)
• “Ganglionic hemorrhages”-Hemorrhages in basal ganglia/thalamus
• “Lobar hemorrhages”-hemorrhage in lobe
• Major causes: hypertension and cerebral amyloid angiopathy
• Other:
• systemic coagulation disorders
• Neoplasms
• Vasculitis
• Aneurysms
• vascular malformations
• chronic hypertension is associated with the development of minute
aneurysms, -Charcot-Bouchard microaneurysms, which rupture occur in vessels
that are less than 300 μm in diameter, mostly, the basal ganglia
• Cerebral autosomal dominant arteriopathy with subcortical infarcts
and leukoencephalopathy(CADASIL)
• Autosomal dominant disorder
• Caused by mutations in the NOTCH3 gene
• NOTCH3 is preferentially expressed in vascular smooth muscle
• Characterized clinically by recurrent strokes
 Vascular malformations
• arteriovenous malformations
• cavernous malformations
• capillary telangiectasias
• venous angiomas
CM
 Capillary telangiectasias (CTSs)
• small areas of abnormally dilated capillaries within otherwise normal
brain tissue. Although CTSs most commonly occur in the pons
Venous angiomas

Common in spinal cord

Mostly silent
 Meningitis:
• Meningitis-inflammatory process of
leptomeninges and CSF
• Meningoenchepatilis-combines this with
inflammation of brain parenchyma
Types:
• Chemical
• Aseptic
• Acute/chronic
 Bacterial meningitis:
• In neonates- E. coli, group B streptococci
• Adolescents/young adult-Neisseria
• Immunosuppressed-Klebsiella, anaerobs
• Immunization against Haemophilus influenzae has
markedly reduced the incidence of this infection in the
developed world
Till 1985, type b H.
influenzae was the most
common cause of meningitis
in children between the ages
of 6 months and 2 years
-resulting in 12,000 to 20,000
cases and over 500 deaths
annually in the U.S
 Complications:
• Ventriculitis
• Focal cerebritis
• venous thrombosis
• Hemorrhagic infarction
• Leptomeningeal fibrosis
• Hydrocephalus
• Chronic adhesive arachnoiditis
• In pneumococcal meningitis, large quantities of the capsular polysaccharide of
the organism produce a gelatinous exudate that promotes arachnoid fibrosis-
chronic adhesive arachnoiditis.
• Waterhouse-Friderichsen syndrome
• results from meningitis-associated septicemia
• Causes: meningococcal/pneumococcal meningitis
• Manifestations: hemorrhagic infarction of the adrenal
glands and cutaneous petechiae
 Diagnosis:
• Spinal tap:
• Cloudy/frankly purulent CSF
• 90,000 neutrophils per cubic millimeter
• Increased protein concentration
• Markedly reduced glucose content
 Viral meningitis
• Less severe
• self-limiting
• Acquired by fecal-oral route
• Treated symptomatically
• Most common cause-enteroviruses(80%)

• Diagnosis:
• lymphocytic pleocytosis
• protein elevation-moderate
• glucose content-normal
 Chemical meningitis
• Rupture of epidermoid cyst in subarachnoid space
• surgical/invasive procedures on brain/spinal cord

• CSF is sterile
• Pleocytosis with neutrophils
• Increased protein concentration
• Sugar content-normal

Dermoid cyst rupture

meningitis
 Spinal tap
• Complications:
• Bleeding from the puncture site
• allergic reaction to the anesthetic
• an infection at puncture site
• headache after the test
• damage to spinal cord nerves
• In healthy adults, ratio of glucose in CSF should be two-third of amount
of glucose found in the blood sample
Causes of low CSF glucose:
(hypoglycorrhachia)
•Bacterial/fungal infection
•Inflammation of the CNS
•Tumor
•subarachnoid hemorrhage
•Hypoglycemia
 Brain abscess
Sources:
• Direct implantation
• Extension from mastoiditis, sinusitis
• Hematogenous from hurt, lung, bones
Risk factors:
• Immunosupression(strep/staph)
• Right to left shunt
• Pulmonary sepsis
 Clinical manifestation:
• Progressive focal deficits
• General signs of raised ICP
• WBC count is raised
• Protein concentration is increased
• Glucose content is normal

• Complications:
• Herniation, ventriculitis, meningitis, and venous
sinus thrombosis
 Subdural Empyema
• Subdural-between dura and arachnoid
• Infection is spreading in subdural space
• Symptoms: fever, headache, neck stiffness,
focal neurologic signs, lethargy, and coma
• Complications:
• Thrombophlebitis-venous occlusion-brain
infarction
 Extradural abscess
• Extradulal/epidural-on or around the dura
• Causes:
• osteomyelitis, sinusitis, preview surgeries
• Sometimes, spinal cord compression
 Paranasal sinuses
sinus age draining innervation
frontal 7(not present at birth) Middle nm Supraorbital(CN V1)

ethmoidal 2 Aec-mnm Nasociliary (CN V1)

Mec-mnm
Pec-snm
Maxillary(biggest) mnm Sup. Alv. Nerves(CN
V2)
sphenoidal 2 Superior nm Post. Ethmoidal nerve
Complications of sinusitis
 Other CNS infections:
• Protozoal diseases (including malaria,
toxoplasmosis, amebiasis, trypanosomiasis),
• Rickettsial infections (such as typhus, Rocky
Mountain spotted fever)
• Metazoal (cysticercosis , echinococcosis)
 Toxoplasmosis
-ring enhancement or nodular
enhancement lesions
- еccentric target sign

Common in HIV
Most common cause of brain abscess in HIV

DD:
CNS lymphoma
 Cerebral amebiasis
• Fatal
• Causes abscess
• Assosciated with Naegleria, acanthamoeba
• Methenamine silver or PAS stains
 Prion disease
• Creutzfeldt-Jakob disease (CJD)-most commom
• Gerstmann-Sträussler-Scheinker syndrome (GSS)
• fatal familial insomnia
• kuru in humans;
• scrapie in sheep and goats;
• mink-transmissible encephalopathy
• chronic wasting disease of deer and elk;
• bovine spongiform encephalopathy

• Diagnosis-western blotting
 Chronic bacterial meningoencephalitis

• TB
• -systemic or isolated(from lung)
• -affects meninges, parenchyma diffusely
• -intraparenchymal mass (tuberculoma) in brain
• Complications:
• Arachnoid fibrosis, Hydrocephalus, obliterative
endarteritis, brain infarction, adhesive arachnoiditis
• Tuberculoma-inside central area of caseous
necrosis surrounded by granulomas;
• calcification may occur in inactive lesion
 Microscopy
• The subarachnoid space contains a gelatinous or fibrinous exudate
• Involves the base of the brain, cisterns, cranial nerves
• discrete, white areas of inflammation scattered over the leptomeninges
• granulomas with caseous necrosis and giant cells
• subarachnoid space arteries-obliterative endarteritis, marked intimal thickening.
 Neurosiphilis
• III stage
• Occurs in 10 % of untreated patients
Patterns:
• Meningovascular neurosyphilis
• paretic neurosyphilis
• tabes dorsalis
 Meningovascular:
• Involves: base of the brain, cerebral
convexities, spinal leptomeninges
• Associated with obliterative endarteritis
(Heubner arteritis), cerebral gummas
 Paretic neurosyphilis
• progressive mental deficits associated with
mood alterations (delusions of grandeur- person's
belief that they are someone other than who they
are, ex: supernatural figure or a celebrity.)
• terminate in severe dementia (general paresis
of the insane)
• Associated with hydrocephalus, granular
ependymitis
General paresis of the insane(paralytic dementia)
 Tabes dorsalis
• damage by the spirochetes to the sensory
nerves in the dorsal root
• Impaired joint position sense, locomotor
ataxia, loss of pain sensation, skin and joint
damage (Charcot joints), “lightning pains”;
absence of deep tendon reflexes.
 Argyll Robertson pupil
• prostitute's pupils-bilateral small pupils that
reduce in size on a near object
• (accommodate, but do not constrict when
exposed to bright light)
 Neuroborreliosis

• aseptic meningitis
• facial nerve palsies
• polyneuropathies
• encephalopathy
 HSV 1
• Most common in children and young adults
• 10% of the affected individuals have a history of
prior herpes
• Involves inferior/medial regions of temporal
lobes, orbital
• Symptoms: alterations in mood/memory/behav
• Cowdry tA viral inclusion bodies in neurons, glia
• Diagnosis: PCR
 HSV 2
• In adults it causes meningitis
• In infants, encephalitis, during vaginal delivery
• During HIV, HSV-2 causes acute, hemorrhagic,
necrotizing encephalitis
Patients with HSV-2 meningitis may
have enlarged mononuclear cells
(Mollaret cells) in the CSF.
HSV-2 meningitis often recurs
(called Mollaret meningitis).
 VZV
• postherpetic neuralgia syndrome after age 60
years
• In immunosuppressed individuals, herpes zoster may
cause acute encephalitis
• Demyelinated lesions followed by necrosis
• Granulomatous arteritis
 CMV
• Common in Immunosuppressed patients
• Causes subacute encephalitis, hemorrhagic necrotizing
ventriculoencephalitis, choroid plexitis, radiculoneuritis
• Infants-periventricular necrosis, followed by microcephaly and
periventricular calcification
 Poliovirus
• meningeal irritation, aseptic meningitis
• When the disease affects the motor neurons of the
spinal cord, flaccid paralysis with muscle wasting
hyporeflexia occurs
• Death-paralysis of the respiratory muscles,
myocarditis
IPV(Salk-1955) vs OPV(Sabin-1961)
 Postpolio syndrome

• develop in patients 25 to 35 years after the resolution of the initial illness

• Characterized by:
• progressive weakness associated with decreased muscle mass and pain, and
has been attributed to superimposed neuronal loss of aging with
inflammatory mechanisms
 Rabies
• Intense brain edema, vascular congestion, neuronal
degeneration, severe inflammation in brainstem
• Negri bodies, the pathognomonic microscopic
finding
• -cytoplasmic, round to oval, eosinophilic inclusions
• found in pyramidal neurons of the hippocampus
and Purkinje cells of the cerebellum
incubation period (1-3 months)
depends on the distance between
the wound and the brain
 Symptoms:
• Slightest touch is painful
• Motor responses progressing to convulsions
• Contracture of the pharyngeal musculature on
swallowing produces foaming at the mouth, which
may create an aversion to swallowing even
water(hydrophobia).
• Meningismus, flaccid paralysis
• Alternating mania and stupor progress to coma and
death from respiratory center failure
Progressive multifocal leukoencephalopathy
(PML)
• caused by the JC polyomavirus;
• infects oligodendrocytes, demyelination is pathologic
effect
• Occurs exclusively in immunosuppressed individuals
SSPE
-always fatal within 1 to 3 years.
cause of death is usually
pneumonia, the pneumonia results
from the extreme weakness and
abnormal muscle control caused
by the disease.
 Fungal ME
• Cryptococcus-inhalation of soil contaminated with pigeon
droppings.
• Histoplasma-contamination of bird or bat droppings(Ohio/
Mississippi Rivers)
• Blastomyces-soil rich in decaying organic matter-USA,
northern Midwest.
• Coccidioides-in soil of endemic areas, arthrospores can
be inhaled in the dust, after a heavy rain (Southwestern
USA, Central/South America)
• Candida spp-acquired in a hospital setting (contaminated
IV line).
Cryptococci
 MS

NMO
Demyelinating
Disseminated
diseases
Acute
encephalomyelitis
Necrotizing
Central pontine
myelinolysis
 MS
• Most common autoimmune demyelinating
disorder(1:1000)
• F:M=2:1
• Age: any, mostly, 20-30 decades
• Relapsing/remitting episodes of variable
duration (weeks to months to years)
• Neurologic defects, followed by gradual,
partial recovery of neurologic function
• Immune response that is directed against the components of
the myelin sheath
• DRB1*1501 allele-3x increased risk of MS

TH1/TH17 T
react against
myelin
antigens

demyelination IFN-γ

recruitment of
macrophages
leukocytes
Risk factors
 Morphology
• multiple, well-circumscribed, depressed,
glassy, gray-tan, irregularly shaped plaques.
• firmer than surrounding white matter-sclerosis
• occur adjacent to the lateral ventricles, in the
optic nerves and chiasm, brainstem, ascending
and descending fiber tracts, cerebellum, and
spinal cord.
 Plaque types:
• Active:
• Ongoing myelin breakdown associated with abundant macrophages,
containing lipid-rich, PAS-positive debris, other inflammatory cells
• Inactive:
• Inflammatory cells slowly disappear. little to no myelin is found,
reduction in the number of oligodendrocyte nuclei; instead, astrocytic
proliferation and gliosis are prominent.
• shadow plaques:
• border between normal and affected white matter is not sharply
circumscribed
 Active plaques patterns:
• pattern I-sharply demarcated and centered on
blood vessels
• pattern II-deposition of immunoglobulin and
complement
• less well demarcated and are not centered on
vessels (patterns III and IV).
• III/IV distinguished by the distribution of
oligodendrocyte apoptosis (III, widespread; IV,
central only).
• only one pair of patterns (I/II or III/IV) may present
in one patient
 Symptoms:
• Initial:
• Paresthesias
• Weakness/clumsiness of limbs
• Visual disturbances

• Fatigue
• Spasticity
• Vertigo
• Erectile dysf.
• Bladder control problems
• Cognitive symptoms: apathy, depression
• Lhermitte sign-electric shocklike pain that
radiates down the spine or into the legs
when the neck is flexed.
 Uhthoff phenomenon
• Excess heat (warm weather, hot bath, fever) may
temporarily exacerbate symptoms and signs
Types:
• Diagnosis:
• IgG levels in the CSF are increased
• oligoclonal IgG bands are usually observed on
immunoelectrophoresis
 Neuromyelitis optica(Devic disease)
• Bilateral optic neuritis and spinal cord demyelination
• Antibodies against aquaporin-4, antibodies injure
astrocytes through complement dependent pathway
• Diagnosis:
• CSF-neutrophilosis
• Vascular deposition of immunoglobulin and complement
• Treatment:
• plasmapheresis or depletion of B cells with anti-CD20
antibody
 Acute disseminated encephalomyelitis (ADEM)
• follows viral infection or, rarely, a viral immunization
• Symptoms: headache, lethargy, coma
• Develop after 1-2 week from infection
• 80 % complete recover, 20 %-death

• - grayish discoloration around white-matter vessels

• - polymorphonuclear leukocytes can be found within
the lesions
• - breakdown of myelin is associated with the
accumulation of lipid-laden macrophage
Acute necrotizing hemorrhagic encephalomyelitis(Hurst
disease)
• fulminant syndrome of CNS demyelination
• Affects young adults and children
• preceded by a recent episode of URI
• Mostly fatal, significant deficits in survivors
• - perivenular distribution of demyelination,
widespread dissemination throughout the CNS
 Central pontine myelinolysis
• Associated with:
• Rapid correction of hyponatremia(in 2-6 days)
• Electrolyte imbalances
 most common cause of dementia in elderly

1. impairment of higher intellectual function

2. alterations in mood and behavior

3. progressive disorientation, memory loss, and aphasia

4. End stage(in 5-10 years) disability, mutism, immobility

Secondary to brain atrophy in Alzhimer
 deposition of
Tau tangles aggregated Aβ
peptides in neutrophil
Protein accumulation
Aggregates of tau,
intracellularly, then
Aβ Plaques
persist extracellularly
after neuronal death
• Senile plaques (neuritic plaques)
• extracellular deposits of Aβ in the grey matter
• Degenerative neural structures and an
abundance of microglia/astrocytes can be
associated with senile plaque deposits
• Neurofibrillary tangles (NFTs)
• aggregates of hyperphosphorylated tau protein
• basophilic fibrillary structures(H&E, silver
(Bielschowsky) staining)
 Granulovacuolar degeneration
• formation of small (~5 μm in diameter), clear
intraneuronal cytoplasmic vacuoles, which
contains an argyrophilic granule.
• it occurs with normal aging, it is most
commonly found in great abundance in
hippocampus and olfactory bulb in AD.
 Hirano bodies
• elongated, glassy, eosinophilic bodies
consisting of paracrystalline arrays of beaded
filaments, with actin as their major
component.
• most commonly found within hippocampal
pyramidal cells.
 Frontotemporal Lobar Degenerations (FTLDs)

• Distinguished from AD:

• Alterations in personality, behavior and language (aphasias) precede
memory loss
• Occur at the same frequency as Alzeheimer disease under 65 years

atrophy reduces gyri

wafer-thin (“knife-
edge”) appearance
Tau

Pick cells/pick bodies

Types

TDP43(RNA-binding neuronal
protein)
loss and gliosis
 Pick disease(lobar atrophy)
• Rare, distinct, progressive dementia
• Early onset
• behavioral changes+alterations in personality
(frontal lobe signs), language disturbances
(temporal lobe signs)
• Mostly sporadic, some familial(mutated tau
protein)
• pattern of lobar atrophy is often prominent
enough to distinguish Pick disease from AD
 Progressive supranuclear palsy
• Cause- Mutations in MAPT gene
• Truncal rigidity, frequent falls, nuchal dystonia;
pseudobulbar palsy, abnormal speech;
• Ocular disturbances-vertical gaze
• Mild progressive dementia
• Fatal within 5 to 7 years of onset
 Corticobasal Degeneration (CBD)

• progressive tauopathy
• -extrapyramidal rigidity, asymmetric motor disturbances (jerking
movements of limbs), impaired higher cortical function (typically in the form
of apraxias).
• with PSP there is a greater burden of tau-containing lesions in brainstem and
deep gray matter, while in CBD the balance is shifted more toward cerebral
cortical involvement.
 Morphology
• “ballooned”neurons- neuronal achromasia
• “tufted astrocytes” -Tau immunoreactivity in astrocytes
• “coiled bodies”- Tau immunoreactivity in oligodendrocytes
• “astrocytic plaques”-tau-positive processes around astrocytes
• tau-positive threads in gray and white matter
basal ganglia structure
located in the midbrain

parts:
pars
compacta(dophaminergic)
pars reticulata(GABAergic)
Diseases involving nigrostriatal system:

• Parkinson disease (PD)

• Multiple system atrophy, commonly associated
with parkinsonism
• Postencephalitic parkinsonism
• Progressive supranuclear palsy and
corticobasal degeneration
• movement disorders that may also show
cognitive impairment
 Symptoms:
• Resting tremor
• Rigidity
• Postural instability
• Bradykinesia
• Dementia
• Sleep problems
• Voiding/defecation problems
• Anosmia
• Seborrheic dermatitis
• Morpology:
• pallor of the substantia nigra and locus ceruleus
• loss of the pigmented, catecholaminergic neurons in
these regions, gliosis
• synuclein-filled Lewy bodies in the nigrostriatal syst.
 Causes:
• Sporadic
• Familial(AD/AR)-10%
• Juvenile
• An acute parkinsonian syndrome:
• MPTP (1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine)destruction of neurons in -the
substantia nigra
• pesticide exposure(caffeine/nicotine may be
protective)
 Treatment:
• Carbidopa/levodopa (mainstay of treatment)
• Amantadine, MAO type B (MAO-B) inhibitors, or, in
few patients, anticholinergic drugs
• Dopamine agonists
• Catechol O-methyltransferase (COMT) inhibitors,
always used with levodopa, particularly when
response to levodopa is wearing off
• Surgery if drugs do not sufficiently control
symptoms or have intolerable adverse effects
• Exercise and adaptive measures
 Multiple System Atrophy
• Cause:
• cytoplasmic inclusions of α-synuclein in
oligodendrocytes
• Patterns:
• 1.parkinsonism(MSA-P, striatonigral
degeneration)
• 2.cerebellar dysfunction (MSA-C,
olivopontocerebellar atrophy)
• 3.autonomic dysfunction (MSA-A, Shy-Drager
syndrome)
• α-synuclein is the major component of the
inclusions
Camptocormia-abnormal, severe and
involuntary forward flexion of the
Pisa syndrome-dystonia
thoracolumbar spine
 HD
• AD
• progressive movement disorders, dementia
• Jerky, hyperkinetic, dystonic movements
• parkinsonism with bradykinesia and rigidity
• Motor symptoms often precede the cognitive
impairment.
• Polyglutamine trinucleotide repeat expansion
disease(CAG)
• Mutation protein huntingtin on chr.4
• Expansions occur during spermatogenesis, so
that paternal transmission is associated with
early onset in the next generation, the
phenomenon of anticipation
• Fatal in 15 years
 Morphology
• Brain is small
• atrophy of the caudate nucleus, putamen
• Lateral/third ventricles are dilated
• Normal HD genes contain 6 to 35 copies of the
repeat;
• when repeat numbers increase, it is associated
with disease
 Friedreich Ataxia

• AR, progressive, spinocerebellar degeneration

• GAA trinucleotide- repeat on chromosome 9q13,
encodes a protein-frataxin
• Beginning in the first decade of life with gait ataxia,
followed by hand clumsiness and dysarthria.
• pes cavus, kyphoscoliosis, hypertrophic CM, cardiac
arrhythmias, CHF
• Concomitant diabetes in 10% of patients
• Most patients become wheelchair-bound within about
5 years of onset;
• Cause of death: intercurrent pulmonary infections/
cardiac disease
 Ataxia-Telangiectasia
• AR, ataxia-telangiectasia mutated (ATM) gene on
chromosome 11q22-q23
• ataxic-dyskinetic syndrome beginning in early
childhood+telangiectasias in conjunctiva/skin,
immunodeficiency
• The lymph nodes, thymus, gonads-hypoplastic
• Complications:
• recurrent sinopulmonary
infections
• dysarthria, eye movement
abnormalities
• lymphoid neoplasms, often T-
cell leukemias; gliomas,
carcinomas
• progressive disorder
• loss of upper motor neurons in the cerebral cortex and lower motor
neurons in the spinal cord and brainstem
• Loss of these neurons results in denervation of muscles
• ALS seems to be caused by an adverse gain-of-function phenotype
associated with mutant SOD1(copper-zinc superoxide dismutase) chr 21
• PASpositive cytoplasmic inclusions, called
Bunina bodies, that appear to be remnants of
autophagic vacuoles.
• Skeletal muscles innervated by the
degenerated lower motor neurons show
neurogenic atrophy
• Early: asymmetric weakness of the hands,
manifested as dropping objects and difficulty
in performing fine motor tasks, and cramping
and spasticity of the arms and legs
• Later, muscle strength and bulk diminish, and
involuntary contractions of individual motor
units, termed fasciculations, occur.
• involves the respiratory muscles, leading to
recurrent bouts of pulmonary infection
 Bulbospinal Atrophy (Kennedy
Syndrome)
• X-linked, adult-onset
• Distal limb amyotrophy and bulbar signs such as atrophy and
• fasciculations of the tongue and dysphagia.
• androgen insensitivity, gynecomastia, testicular atrophy, and
oligospermia.
• degeneration of lower motor neurons in the spinal cord
• brainstem.
• The gene defect is expansion of a CAG/polyglutamine repeat in the
androgen receptor
• nuclear inclusions containing aggregated androgen receptor can be
found, although it remains unclear whether these inclusions are
critical to cellular injury.71
 CNS Tumors:
• 50 % of brain/spinal cord tumors are metastatic
• 2-3 % of cancer death in US
• 20% of childhood cancers
• Approximately 70% of all brain tumors are benign, 30% of all brain tumors are
malignant
• Approximately 58% of all brain tumors occur in females, 42% of all brain tumors occur
in males
• 70% childhood CNS tumors arise in the posterior fossa
• Tumors in adults arise within the cerebral hemispheres above the tentorium
 benign meningioma

adults

malignant glioblastoma
Most common
brain tumors

Pilocytic astrocytoma
(17.7%)
children
Glioma, malignant (14.5%)
Embryonal tumors (12.7%)
 Gliomas
• most common group of primary brain tumors
• Astrocytomas
• Oligodendrogliomas
• Ependymomas
 No grade I diffuse infiltrative
astrocytoma!!!

Diffuse astrocytoma g. II
Diffuse Anaplastic astrocytoma g.III
Glioblastoma g.IV
Astrocytoma

Local
 Spectrum: OLD classification!
• grade I/IV pilocytic astrocytoma
• grade II/IV diffuse astrocytoma
• grade III/IV anaplastic astrocytoma
• grade IV/IV glioblastoma
histologic separation
of polocytic astrocytoma from
other astrocytomas is
supported
by the rarity of TP53
mutations or molecular
signatures
of infiltrating astrocytomas
 Infiltrating Astrocytomas
• 80% of adult primary brain tumors in adults
• Commonly, in 40-60 years
• Location: cerebral hemispheres, cerebellum,
brainstem, spinal cord
• Clinical manifestations:
• seizures, headaches, focal neurologic deficits
• gemistocytic astrocytoma(variant of anaplastic a.)
• predominant neoplastic astrocyte shows a brightly eosinophilic cell body from
which emanate abundant, stout processes.
• Can progress to glioblastoma
 New onset tumor
primary
in elderly
glioblastoma
Progressed low
secondary grade astrocytoma
in young adults

molecular classic proneural neural mesenchymal

subtypes
mutation PTEN TP53 neuronal NF1
markers: NEFL,
GABRA1, SYT1,
and SLC12A5
CDKN2A IDH1/IDH2

Most common
type in II
glioblastoma
• pseudo-palisading pattern in GB -Tumor cells collect along the edges of the
necrotic regions
• Gliomatosis cerebri
• diffuse glioma with extensive infiltration of multiple regions of the brain,
in some cases the entire brain
 GFAP

• GFAP gene codes GFAP, which distinguishes

astrocytes from other neuronal cells
• GFAP gene mutation occurs in Alexander
disease(leukodystrophy)
Alternation in BRAF signaling
Targeted BRAF inhibitors are effective
Morphology: biphasic parts-
Microcystic and fibrillary areas
Rosenthal fibers-eosinophilic granular bodies
mutations of the isocitrate
dehydrogenase genes (IDH1 and IDH2) in 90
%
Fried egg appearance
Calcification, present in 90% of
these tumors, ranges from
microscopic foci to massive
depositions
 Retinoblastoma
• Can run in families
• Usually happens before age 2
• In 25% both eyes are affected
• Manifestations:
• white pupil, crossed eyes, vision problems
• Treatment includes surgery, chemotherapy,
and sometimes radiation therapy
Verocay bodies
• NF1—mutation on chromosome 17 coding for
neurofibromin
• NF2—mutation on chromosome 22 coding for
merlin
• Both proteins act as tumor suppressors
 NF 1
• AD
• Characterized by:
• neurofibromas (plexiform and solitary) gliomas
of the optic nerve
• pigmented nodules of the iris (Lisch nodules)
• cutaneous hyperpigmented macules (café au
lait spots)
• NF1 gene, located at 17q11.2, encodes neurofi
bromin—a large protein with a GTPase-
activating domain that inhibits RAS.
 NF 2
• Tumors:
• bilateral eighth-nerve schwannomas
• multiple meningiomas
• Gliomas, typically ependymomas of the spinal cord
• Non neoplastic:
• Ingrowth of Schwann cells into the spinal cord
(schwannosis)
• meningioangiomatosis (a proliferation of meningeal cells
and blood vessels that grows into the brain)
• Glial hamartia (microscopic nodular collections of glial
cells at abnormal locations, often in the superfcial and
deep layers of cerebral cortex).
 Tuberous sclerosis
• Hamartomas
• Benign neoplasms
• Infantile spasms
• renal angiomyolipomas
• retinal glial hamartomas
• pulmonary lymphangioleiomyomatosis
• cardiac rhabdomyomas
• Cysts in liver, kidneys, and pancreas.
• Cutaneous lesions include angiofibromas, localized leathery
thickenings (shagreen patches), hypopigmented areas (ash-leaf
patches), subungual fibromas.
• shagreen patches or ash leaf spots identified
with Wood lamp occur in >80% of case
• (TSC1) is found on chromosome 9q34, and it
encodes a protein known as hamartin;
• the more commonly mutated tuberous
sclerosis locus (TSC2) is at 16p13.3 and
encodes tuberin
 Von Hippel–Lindau Disease
• hemangioblastomas
• cysts involving the pancreas, liver, and kidneys
• renal cell carcinoma
• Pheochromocytoma
• Hemangioblastomas in the cerebellum, retina
 Peripheral Neuropathies:
• Mononeuropathies
• Polyneuropathies
• Mononeuritis multiplex
• Polyradiculoneuropathies
 Cause:
• Inflammatory diseases
• Infections
• Metabolic changes
• Toxic injury
• Trauma
• (para)neoplastic disease
• Inherited gene defects
Inflammatory: Guillain-Barré Syndrome (Acute Inflammatory
Demyelinating Polyneuropathy)

• rapidly progressive ascending paralysis

• self-limited
• begins 5-20 days after a banal infectious
disorder, surgery, or vaccination
• If weakness progresses for > 2 months, chronic
Inflammatory demyelinating polyneuropathy
is diagnosed
• Campylobacter jejuni
• Enteric viruses
• Herpesviruses (CMV, EBV)
• Mycoplasma species
• Zika virus
• COVID-19
 Red flags:
• Forced vital capacity < 15 mL/kg-
endotracheal intubation is indicated
• Inability to lift the head off the pillow by
flexing the neck is another danger sign;
-develops simultaneously with phrenic
nerve weakness
• Oliguria
Facial/oropharyngeal muscle
weakness results in
dehydration/undernutrition

2% -5% of affected
patients die of:
respiratory paralysis
autonomic instability
cardiac arrest

Common in Hodgkin lymphoma

 Miller-Fisher syndrome
• unusual variant
• may cause only ophthalmoparesis, ataxia,
and areflexia
• Recovery in 2-4 weeks
• In 3 %, relapses occur
 DD:
• Myasthenia gravis-intermittent, worsened
by exertion.
• Botulism -fixed dilated pupils (in 50%) and
prominent cranial nerve dysfunction with
normal sensation.
• Poliomyelitis - occurs in epidemics.
• Tick paralysis- causes ascending
paralysis but spares sensation
• EMG:
• slow nerve conduction velocities
• segmental demyelination
• CSF:
• albuminocytologic dissociation (increased
protein but normal white blood cell count)
• may not appear for up to 1 week
• does not develop in 10% of patient
 Treatment:
• IV immune globulin (IVIG)
• plasma exchange
 Chronic Inflammatory Demyelinating
Poly(radiculo)neuropathy

• Continues more than 2 month

• Most common cause of CIPN
• Symmetrical mixed sensorimotor
polyneuropathy
• evolves over years, with relapses and remissions
• Treat: steroids, IV Ig, plasma exchange
• Differ from GBS:
• Time course, steroid response
 Infectious neuropathies:
• VZV
• Leprosy
• Diphteria
• HIV
• Lyme
most severe in the
relatively cool distal
extremities and in the
face because
lower temperatures
favor mycobacterial
growth

involves pain fibers,

patients frequently
develop injuries
 Diphtheria
• Common during incomplete immunization
• Diphtheria exotoxin damages Peripheral nerves
• Results in:
• bulbar and respiratory muscle dysfunction
-Latent phase in sensory ganglia
-Reactivation in keratinocytes of
skin-results in shingles in sensory
dermatomes(thoracic/trigerminal)
-ascending distal symmetric
sensorimotor polyneuropathy
most common cause of peripheral neuropathy
numbness
loss of pain
sensation
difficulty with
balance
Paresthesias
dysesthesias
 Traumatic
neuropathies
Carpal tunnel syndrome
• Tinel sign-median nerve paresthesias are
reproduced by tapping at the volar surface
of the wrist over the site of the median
nerve in the carpal tunnel.
• Phalen sign-reproduction of tingling with
wrist flexion or with direct pressure on the
nerve at the wrist in a neutral position
 Charcot-Marie-Tooth
(peroneal muscular atrophy)

• Most common inherited peripheral neuropathies

• Frequency: 1 in 2500 people
• Symptoms: distal muscle atrophy, sensory loss, and foot
deformities
• Types: AD, X-linked
• Mostlu begin in childhood
 Myasthenia gravis
• Episodic muscle weakness and easy fatigability
caused by autoantibody- and cell-mediated
destruction of acetylcholine receptors
• Bimodal age distribution:
Most common NMJ
• 20- 40; 50-80 disorder

• Suspect during:
• Ptosis, diplopia, muscle weakness
• Symptoms worsen during activity, improve with
rest
Autoantibodies to postsynaptic ACh receptor
 Cause:
• antibodies to postsynaptic acetylcholine
receptors (AChR)
• antibodies to muscle-specific receptor
tyrosine kinase (MuSK)-focal symptoms
• 10% no known cause
 associated with:
• abnormalities of the thymus:
• Cancer-10%, hyperplasia-30%
• autoimmune hyperthyroidism
• RA
• SLE
• Pernicious anemia
 Symptoms are triggered by:
• Infection
• Surgery
• Drugs:
• Aminoglycosides
• Quinine
• magnesium sulfate
• Procainamide
• calcium channel blockers
• Immune checkpoint inhibitors
 Rare types:
• Ocular: only extraocular muscles are involved
• Neonatal: IgG passes from mother to child
-self limited in several weeks
• Congenital(AR):
• Reduced ACh resynthesis due to choline
acetyltransferase deficiency
• End-plate acetylcholinesterase deficiency
• Structural abnormalities in postsynaptic receptor
 milkmaid's grip
• Uncontrollable(alternation in strong and weak) rhythmic
squeezing of the examiner's fingers when trying to grip
and hold the fingers
Myasthenic crisis
severe generalized quadriparesis or
life-threatening respiratory muscle
weakness
occurs in about 15 to 20%
Triggered by infection
Cholinergic crisis
muscular weakness that can result when
the dose of anticholinesterase drugs is too
high
muscle fasciculations, increased
lacrimation and salivation, tachycardia,
and diarrhea
 Diagnosis:
• AChR antibody levels
• Anti-MuSK antibodies
• EMG
• Imaging for thymoma
• Screening for autoimmune diseases
 Icepack test
• Myasthenia weakness lessens in cooler
temperature
• Does not work if patients have ophthalmoparesis
 Treatment:
• anticholinesterase drugs
• Immunosuppressants
• Corticosteroids
Reverses symptoms
• plasma exchange (pyridostigmine)

• IV immune globulin
• Thymectomy
 Eaton-lambert syndrome
• Paraneoplastic syndrome(small/oat cell lung cancer) Rare
• antibodies block acetylcholine release by inhibiting presynaptic calcium
channel

• Assosciated with:
• Vitiligo
• Thyroid diseases

• Treatment is first directed at the underlying cancer and sometimes induces

remission
 Clinical manifestations:
• Proximal muscle weakness
• Autonomic symptoms (dry mouth, constipation,
impotence)
• Hyporeflexia
• Improves with muscle use
• Weakness spares ocular and bulbar muscles

In contrast to myasthenia gravis,

rapid repetitive stimulation
increases muscle response
Raynaud phenomenon

• Arteriolar (small vessel) vasospasm in response to cold/

stress:
• Color change:
• white (ischemia) to blue (hypoxia) to red (reperfusion).
• Mostly affects fingers and toes.
• Raynaud disease - idiopathic
• Raynaud syndrome – secondary to mixed connective
tissue disease, SLE, CREST syndrome (limited form of
systemic sclerosis).
• Digital ulceration (critical ischemia) seen in 2° Raynaud
syndrome.
• Treat with calcium channel blockers
Inflammatory Myopathies

Dermatomyositis

Polymyositis

Inclusion body
myositis
 Dermatomyositis
• Involves skin, skeletal muscles(proximal muscle)
• Hallmark: perifascicular atrophy.
• Clinically similar to polymyositis, but also involves Gottron papules A ,
photodistributed facial
• erythema (eg, heliotrope [violaceous] edema of the eyelids B ), “shawl and
face” rash C ,
• mechanic’s hands (thickening, cracking, irregular “dirty”-appearing marks
due to hyperkeratosis
• of digital skin D. risk of occult malignancy. Perimysial inflammation and
atrophy with CD4+ T
• cells.
small blood vessels telangiectasias Deposition of (C5b-9)
contributes to muscle (dilated capillary within
injury. loops) in the nail folds, capillary beds.
eyelids, and gums and Type I interferons is
as dropout of capillary seen in muscle
vessels in skeletal
muscle and in leukocytes.
 Specific antibodies lead to specific
symptoms
Anti-Mi2 antibodies Anti-P155/P140
Anti-Jo1 antibodies
(directed against a antibodies (directed
(directed against the
helicase implicated against several
enzyme histidyl
in nucleosome transcriptional
t-RNA synthetase)
remodeling) regulators)

Interstitial lung
disease, nonerosive
paraneoplastic
Gottron papules and arthritis, and a skin
and juvenile cases of
heliotrope rash rash described
dermatomyositis
as “mechanic’s
hands.”
 Morphology:
• Distinctive pattern in which myofiber atrophy is
accentuated at the edges of the fascicles—
perifascicular atrophy
 Polymyositis
• Progressive symmetric proximal muscle weakness
• Endomysial inflammation with CD8+ T cells
• Most often involves shoulders Diagnosis of exclusion:
• T cell–mediated autoimmune disease 1. Lacks skin changes od
dermatomyositis
Rest is same
2. vascular injury does
not have a major role in
the pathogenesis
of polymyositis
 Diagnosis for P/D:
• Nonspecific: ⊕ ANA
• Increased CK
• Specific: ⊕ anti-Jo-1 (histidyl-tRNA synthetase)
• ⊕ anti-SRP (signal recognition particle)
• ⊕ anti-Mi-2 (helicase)
 Inclusion Body Myositis

• Most common inflammatory myopathy in patients older than age 65

years.
• slowly progressive muscle weakness
• Most severe in the quadriceps and the distal upper extremity muscles.
• Dysphagia from esophageal and pharyngeal muscle
• modestly elevatedCK;
• most myositis associated autoantibodies are absent
• Antibody to cytosolic 5’-nucleotidase 1A (cN1A) in 50 %
 excoriation
• Traumatic lesion breaking the epidermis and
causing a raw linear area (i.e., deep scratch);
often self-induced(OCD)
 Lichenification
• Thickened and rough skin characterized by
prominent skin markings (as lichen on a tree
trunk)
 Macule
• Circumscribed lesion, 5 mm or smaller in
diameter, characterized by flatness and
distinguished by coloration (patch is greater
than 5 mm)
 Papule
• Elevated dome-shaped or flat-topped lesion 5
mm or less across
• nodule is greater than 10 mm
 Plaque
• Elevated flat-topped lesion, usually greater
than 5 mm across (may be caused by
coalescent papules)
 Pustule
• Discrete, pus-filled, raised lesion
 Scale
• Dry, horny, platelike excrescence; usually the
result of imperfect cornification
 Vesicle/Bulla
• Vesicle-Fluid-filled raised lesion 5 mm
• Bulla is greater than 5 mm
• Blister is the common term for either
 Wheal
• Itchy, transient, elevated lesion with variable
blanching and erythema formed as the result
of dermal edema
 Spongiosis
• Intercellular edema of the epidermis
 Ulceration
• Discontinuity of the skin showing complete
loss of the epidermis revealing dermis or
subcutis
 Vacuolization
• Formation of vacuoles within or adjacent to
cells; often refers to basal cell–basement
membrane zone area
 onycholysis
• Separation of nail plate from nail bed
 Freckles
• 1 mm macules
• contain aggregated melanosomes within the
cytoplasm of melanocytes
• Most common pigmentation
• Darken in sun
 Lentigo
• Benign localized hyperplasia of melanocytes
occurring at all ages
• not darken when exposed to sunlight
 Melanocityc nevus
• neoplasm of melanocytes
• Become more prominent during pregnancy,
indicating a degree of hormone sensitivity.
Congenital nevus
Blue nevus
Spitz nevus
Halo nevus
Dysplastic nevus
 Melanoma
• Skin
• Oral mucosa
• Anogenital mucosal surfaces
• Esophagus
• Meninges
• Eye
 Symptoms:
• Early manifestations-itching, pain, Change in
color, size, shape, pigmentation
• Borders-irregular, notched, not smooth, round,
and uniform as in melanocytic nevi.
• most important warning signs-
 Risk factors:
• Sun exposure(repeated blistering sunburns)
• Repeated tanning UVA or psoralen plus UVA
• Nonmelanoma skin cancer
• Family/personal history
• Fair skin, freckling
• Atypical moles, particularly > 5
• Increased numbers of melanocytic nevi
• Immunosuppression
• Occurrence of lentigo maligna
• Congenital melanocytic nevus > 20 cm
• Atypical mole syndrome (dysplastic nevus)
 4 main types:
• Superficial spreading melanoma
• Nodular melanoma
• Lentigo maligna melanoma
• Acral-lentiginous melanoma

• Rarely, all subtypes can be amelanotic

Occurs in <10%
Amelanosis leads to late diagnosis, worst prognosis
 outcome based on the following
variables:
• tumor depth (the Breslow thickness);
• number of mitoses;
• Evidence of tumor regression
• presence/number of tumor infiltrating
lymphocytes (TILs);
• gender;
• location (central body or extremity).
Brislow
Paraneoplastic syndrome in GI
cancers
 Acanthosis nigricans
• Velvet like texture
• Paraneoplastic syndrome(growth factors)
• GI adenocarcinoma
• Obesity, achondroplasia
• Familial- FGFR3 mutation
 fibroepithelial polyp

• acrochordon, squamous papilloma, skin tag

• Sporadic
• Seen together in Birt-Hogg-Dubé syndrome
• Associated with diabetes, obesity, and intestinal polyposis
• Become more numerous or prominent during pregnancy
 Epitheloid cyst(wen)
• Invagination and cystic expansion of the
epidermis or a hair follicle
• cysts are filled with keratin and lipid-containing
debris derived from sebaceous secretions
Menzies method
 SSC
• second most common tumor
• arising on sun-exposed sites in older people
• <5% of these tumors metastasize to regional nodes
• Cause: DNA damage induced by exposure to UV light

• Risk:
• immunosuppression as a result of chemotherapy or organ transplantation
• industrial carcinogens (tars and oils)
• chronic ulcers and draining osteomyelitis
• old burn scars, ingestion of arsenicals, ionizing radiation, and (in the oral
cavity)
• tobacco and betel nut chewing

• Prognosis:
• The 5-year survival is 99 percent when detected early
 BSC
• most common invasive cancer in humans
• 1 mln cases per year in USA
• <0.5% are locally aggressive
• occur at sun-exposed sites in lightly pigmented elderly adults
 basal cell nevus or Gorlin syndrome
• AD
• multiple basal cell carcinomas
• often before age 20
• accompanied by other tumors (medulloblastomas and ovarian fibromas)
• pits of the palms and soles
• certain developmental abnormalities
 Dermatofibroma
• Benign dermal neoplasms of uncertain lineage
• Occur on the legs of middle-aged women
• Firm, tan to brown papules
• Dimple inward on lateral compression
Dermatofibrosarcoma protuberans
• locally aggressive
• can recur
• rarely metastasize
• Sometimes ulcerate
• Arise most frequently on the trunk
• balanced translocation between genes:
• collagen 1A1 (COL1A1) and platelet derived growth
factor-β (PDGFB)
• Treatment-targeted tyrosine kinase inhibitor
imatinib mesylate(lifelong)
• S

Storiform pattern
Honeycomb pattern
 Mycosis fungoidosis-Cutaneous T cell
lymphoma (CTCL)
• mycosis fungoides-chronic proliferative
process
• mycosis fungoides d’emblée-more aggressive
nodular eruptive variant
• Confused with psoriasis, fungal nodules
• seeding of the blood by malignant T cells is
accompanied by diffuse erythema and scaling
of the entire body surface (erythroderma), a
condition known as Sézary syndrome
Sézary-Lutzner cells
 Mastocytosis
• Increased numbers of mast cells in skin/organs
• urticaria pigmentosa-localized cutaneous form in children,
shortly after birth
• 10 % have systemic disease
• Signs/symptoms are due to histamine, heparin

• Triggers of pruritus/flushing:
• certain foods, temperature changes, alcohol, and certain drugs
(morphine, codeine, aspirin);
• watery nasal discharge (rhinorrhea); rarely, gastrointestinal or
nasal bleeding, possibly due to the anticoagulant effects of
heparin; and bone pain as a result of osteoblastic and
osteoclastic involvement.
 Types:
• urticaria pigmentosa-localized cutaneous form
in children, shortly after birth
• Solitary mastocytomas-one or several pink to
tan-brown nodules pruritic or blister
• systemic mastocytosis-similar to urticaria
pigmentosa, accompanied by mast cell
infiltration of bone marrow,liver, spleen, and
lymph nodes
• Darier sign- localized area of dermal edema
and erythema (wheal) that occurs when lesion
skin is rubbed
Molluscum contagiosum
 Ichthyosis

• Impaired epidermal maturation

• Excessive keratin buildup (hyperkeratosis)
results in fish-like scales
• Defective desquamation, leading to retention
of abnormally formed scale
• Congenital -apparent either at or around the
time of birth.
• Acquired (vulgaris)-association with lymphoid,
visceral malignancies
 Types:
• Ichthyosis vulgaris (AD or acquired)
• Congenital ichthyosiform erythroderma (AR)
• Lamellar ichthyosis (AR)
• X-linked ichthyosis(deficiency of steroid sulfatase,
which removes of proadhesive cholesterol sulfate
secreted into the intercellular spaces.
• Accumulation of cholesterol sulfate results in
persistent cell-to-cell adhesion within the stratum
corneum, hindering the desquamation process)
 Urticaria(hives)
• localized mast cell degranulation, dermal
microvascular hyperpermeability
• Wheals-rise to pruritic edematous plaques
• Angioedema-deeper edema of both the dermis
and the subcutaneous fat
• Persistent episodes may herald an underlying
disease (e.g., collagen vascular disorders,
Hodgkin lymphoma)
 Causes:
Ig E dependent Ig E independent

pollens opiates

food Antibiotics, aspirin, curare

drugs C1 deficiency

Insect venom Contrast media

 Red flags

• Angioedema (swelling of face, lips, tongue)

• Stridor, wheezing, respiratory distress
• Hyperpigmented lesions, ulcers, or
urticaria that persist > 48 hours
• Signs of systemic illness (eg, fever,
lymphadenopathy, jaundice, cachexia)
 Acute eczematous dermatitis
• (1) allergic contact dermatitis
• (2) atopic dermatitis
• (3) drugrelated eczematous dermatitis
• (4) photoeczematous dermatitis
• (5) primary irritant dermatitis
 Erythema multiforme
• self-limited disorder
• hypersensitivity reaction to infections, drugs,
diseases
Infections drugs
herpes simplex sulfonamides
mycoplasmal infections penicillin
histoplasmosis Barbiturates
coccidioidomycosis salicylates,
typhoid, hydantoins
leprosy antimalarials
 Stevens-Johnson syndrome
• An extensive and symptomatic febrile form of
erythema multiforme
• Erosions/hemorrhagic crusts involve:
• Lips, oral mucosa, conjunctiva, urethra, genital,
perianal
 Psoriasis
• Affects:
• skin of the elbows, knees, scalp, lumbosacral
areas, intergluteal cleft, glans penis
• pink to salmon-colored plaque covered by
loosely adherent scale(silver-white in color)
• associated with arthritis, myopathy,
enteropathy, spondylitic joint disease, or the
acquired immunodeficiency syndrome
• The stratum granulosum is thinned or absent,
and extensive overlying parakeratotic scale is
seen.
• Auspitz sign-bleeding points when the scale is
lifted from the plaque
 Sebhorreic dermatitis
• scalp, forehead (especially the glabella),
external auditory canal, retroauricular area,
nasolabial folds, and the presternal area)
• Dandruff is the common clinical expression
• Associate with HIV, Leiner disease
• Increased risk with parkinson, Malasezia
furfur(fungi)
 Lichen planus
• self-limited
• Commonly resolves spontaneously 1 to 2 years
after onset
• leaves zones of postinfammatory
hyperpigmentation
• Oral lesions may persist for years
• Squamous cell carcinoma has been noted to
occur in chronic mucosal and paramucosal
lesions
• Wickham striae - papules are often highlighted
by white dots or lines, are created by areas of
hypergranulosis.
• Koebner phenomen-appearance of new skin
lesions on previously unaffected skin
secondary to trauma
• colloid or Civatte bodies
 Pemphigus
• Autoantibodies that result in the dissolution of
intercellular attachments within the epidermis
and mucosal epithelium.
• Pemphigus vulgaris- most common type (80%)
• Sites-mucosa, skin, scalp, face, axilla, groin,
trunk.
• oral ulcers persist for months before skin
involvement appears
• Primary lesions- superficial vesicles and bullae
that rupture easily, leaving shallow erosions
covered with dried serum and crust
• Pemphigus vegetans –rare
• presents not with blisters but with large, moist,
verrucous (wart-like), vegetating plaques
studded with pustules on the groin, axillae,
and flexural surfaces
• Pemphigus foliaceus -more benign form
• Endemic in Brazil (called fogo selvagem)
• Sites- scalp, face, chest, back, mucous memb.
• Bullae are so superficial that only zones of
erythema and crusting, sites of previous blister
rupture resulting in superficial erosions
• Pemphigus erythematosus(Senear-Usher
syndrome) –
• localized, less severe form of pemphigus
foliaceus
• Involve malar area of the face in a lupus
erythematosus–like fashion
• Paraneoplastic pemphigus
• associated with various malignancies, most
commonly non- Hodgkin lymphoma.
 Morphology:
• Acantholytic cells dissociate from one another,
lose their polyhedral shape and become
rounded
 Cause:
• IgG autoantibodies against desmogleins, and
show linkage to specific HLA types
• By direct immunofluorescence, lesional sites
show a characteristic net-like pattern of
intercellular IgG deposits.
• IgG is usually seen at all levels of the
epithelium in pemphigus vulgaris, but tends to
be more superficial in pemphigus foliaceus
 Bullous pemphigoid
• affects elderly individuals
• Sites-skin/skin+mucosa:
• -thighs, flexor surfaces of the forearms, axillae,
groin, and lower abdomen.
• lesions are tense bullae, filled with clear fluid,
on normal or erythematous skin
• Heal without scarring, if not infected
• The separation of bullous pemphigoid from
pemphigus is based on the identification of
subepidermal, nonacantholytic blisters
• Eosinophils showing degranulation are
typically detected directly beneath the
epidermal basal cell layer
• The vacuolated basal cell layer eventually gives
rise to a fluid-filled blister
 Pathogenesis
• linear deposition of immunoglobulin and
complement in the basement membrane zone
 Dermatitis herpetiformis
• Urticaria+grouped vesicles
• affects predominantly males, 30-40y
• Associated with intestinal celiac disease and
responds to a gluten-free diet
• Genetically predisposed individuals develop lgA
antibodies to dietary gluten (derived from the
wheat protein gliadin).
• The antibodies cross-react with reticulin, a
component of the anchoring fibrils that tether the
epidermal basement membrane to the superficial
dermis.
• The resultant injury and inflammation produce a
subepidermal blister
• granular deposits of lgA selectively localized in the
tips of dermal papillae
• Pruritic, bilateral, symmetric and grouped,
involving preferentially the extensor surfaces,
elbows, knees, upper back, and buttocks
 Epidermolysis bullosa
• Inherited defects in structural proteins that
lend mechanical stability to the skin
• Complication -Squamous cell carcinoma
• "onion skin approach" — classification by
determination of the level of blister formation,
usually by immunofluorescence antigen
mapping and/or transmission electron
microscopy
 Classification:
• 1.Epidermolysis bullosa simplex (EBS) – Intraepidermal
cleavage plane, within the basal keratinocytes (basal EBS) or
above the level of basal keratinocytes (suprabasal EBS)
• 2.Junctional epidermolysis bullosa (JEB) – Cleavage plane
within the lamina lucida of the dermoepidermal junction
• 3.Dystrophic epidermolysis bullosa (DEB) – Cleavage plane
below the lamina densa, within the upper papillary dermis at
level of anchoring fibrils
• 4.Kindler syndrome – Multiple cleavage planes
(intraepidermal, intralamina lucida, or sublamina densa)
• 5. Epidermolysis bullosa acquisita (EBA)-nongenetic,
autoimmune
 Porphyria
• Porphyrins are pigments normally present in
hemoglobin, myoglobin, cytochromes
• Types:
• (1) congenital erythropoietic porphyria
• (2) erythrohepatic protoporphyria
• (3) acute intermittent porphyria
• (4) porphyria cutanea tarda
• (5) mixed porphyria
 Skin manifestations:
• urticaria and vesicles that heal with scarring
• exacerbated by exposure to sunlight
• Microscopy: subepidermal vesicle with
associated marked thickening of the walls of
superficial dermal vessels
 Acne vulgaris
• Physiologic hormonal variations and alterations in hair
follicles, particularly sebaceous gland.
• Induced/exacerbated:
• by drugs (corticosteroids, adrenocorticotropic hormone,
testosterone, gonadotropins, contraceptives,
trimethadione, iodides, and bromides)
• Occupational contactants (cutting oils, chlorinated
hydrocarbons, and coal tars)
• Occlusive conditions: heavy clothing, cosmetics, tropical
climates
• Treatment-synthetic vitamin A derivative 13-cisretinoic
acid (isotretinoin)
 Morphology:
• components contributing acne:
• (1) changes in keratinization, development of a
keratin plug blocking outflow of sebum to the skin
surface;
• (2) hypertrophy of sebaceous glands with puberty
or increased activity due to hormonal stimulation;
• (3) lipase-synthesizing bacteria (Propionibacterium
acnes) break down sebaceous oils, liberating highly
irritating fatty acids and resulting in the earliest
inflammatory phases
• (4) inflammation of the follicle associated with
release of cytotoxic and chemotactic factors
 Rosacea
• Stages:
• (1) flushing episodes (pre-rosacea)
• (2) persistent erythema and telangiectasia
• (3) pustules and papules
• (4) rhinophyma—permanent thickening of the
nasal skin by confluent erythemaous papules
and follicular prominence.
• -patients have high cutaneous levels of the
endogenous antimicrobial peptide cathelicidin
 Panniculitis
• Erythema nodosum
• Erythema induratum
• Weber-Christian disease
• Factitial panniculitis
• SLE panniculitis
 Erythema nodosum
• associated with:
• Infections (β- hemolytic streptococci, TB
coccidioidomycosis, histoplasmosis, leprosy)
• Drugs (sulfonamide, contraceptives)
• Sarcoidosis
• Inflammatory bowel disease
• Malignant neoplasms
• Fever, malaise
• Over weeks, lesions usually flatten and become
bruiselike, leaving no residual clinical scars,
while new lesions develop.
 Erythema induratum
• affects adolescents and menopausal women
• Sometimes, hypersensitivity response to TB
• necrotizing vasculitis affecting small- to
medium-sized arteries and veins in deep
dermis and subcutis.
 Weber-Christian disease

• rare form of lobular, nonvasculitic panniculitis

seen in children and adults
• Crops of erythematous plaques or nodules,
predominantly on the lower extremities,
created by deep-seated foci of inflammation
with aggregates of foamy histiocytes mixed
with lymphocytes, neutrophils, giant cells
 Factitial panniculitis
• secondary panniculitis caused by self-inflicted
trauma or injection of foreign or toxic
substances.
 Warts
• Caused by papilomavirus
• Transmission-direct contact between
individuals or auto-inoculation.
• self-limited, regressing spontaneously within 6
months to 2 years
 Impetigo
• superficial bacterial infection of skin
• It is highly contagious
• Types(caused by staph):
• impetigo contagiosa
• impetigo bullosa

• accumulation of neutrophils beneath the stratum

corneum, often producing a subcorneal pustule
• bacterial production of a toxin cleaves desmoglein 1,
the protein responsible for cell-to-cell adhesion within
the uppermost epidermal layers
 Molluscum contagiosum
• common, self-limited viral disease of the skin
• caused by a poxvirus(one of the largest viruses in nature)
• spread by direct contact, among children and young adults
The eye
The orbit
 Proptosis
• displace the eye forward
• Types: axial (directly forward) or positional
 Graves opthalmolopathy
• Proptosis is caused by the accumulation of
extracellular matrix proteins and variable
degrees of fibrosis in the rectus muscles
 Inflammation of orbits
• Causes:
• From sinusitis
• During Wegener granulomatosis
• Idiotahthic inflammation(during connective
tissue disorders, vasculitis)
 Neoplasms

• Mostly, vascular in origin:

• capillary hemangioma
• lymphangioma
• cavernous hemangioma

• Encapsulated:
• pleomorphic adenoma of the lacrimal gland, dermoid cyst
• Neurilemmoma

• Other:
• Non Hodgkin lymphoma
• Orbital lymphomas
• metastatic prostatic carcinoma may present
clinically like idiopathic orbital inflammation;
• metastatic neuroblastoma and Wilms tumor—
richly vascular neoplasms—may produce
characteristic periocular ecchymoses.
• Neoplasms may also invade from the sinuses
into the orbit
• elements within the eyelid generate critical
components of the tear film.
• If the drainage system of the sebaceous glands
is obstructed by chronic inflammation at the
eyelid margin (blepharitis) or by neoplasm,
then lipid may extravasate into surrounding
tissue and provoke a granulomatous response
producing a lipogranuloma, or chalazion
 Neoplasms
• basal cell carcinoma(Most common)
• sebaceous carcinoma(II most common)
• squamous cell carcinoma(III)
• primary melanomas are rare
• Subaceous carcinoma(mimics chalazion)
• Kaposi sarcoma in AIDs, either the eyelid or
the conjunctiva is affected
• The conjunctiva in the fornix is a
pseudostratified columnar epithelium rich in
goblet cells.
• The fornix contains accessory lacrimal tissue,
and the ductules of the main lacrimal gland
pierce through the conjunctiva in the fornix
superiorly and laterally.
• The lymphoid population of the conjunctiva is
most noticeable in the fornix
Granulomatous conjuctivitis in
sarcoidosis
 conjunctival scarring
• Chlamydia trachomatis
• Exposure to alkalis

•
•
• ocular cicatricial pemphigoid
• dry eye results from a
deficiency in the aqueous
component of the tear film
generated by the accessory
lacrimal glands
Nasolacrimal duct obstruction in infants
•Excessive tearing
•Redness
•Recurrent eye infection or
inflammation (pink eye)
•Painful swelling
•Crusting of the eyelids.
•Mucus or pus discharge
•Blurred vision
 Pinguecula/pterygium
• appear as submucosal elevations on the
conjunctiva
• result from actinic damage
• located in sun-exposed regions of the
conjunctiva
 Pterygium
• Originates in the conjunctiva astride the
limbus.
• formed by a submucosal growth of
fibrovascular connective tissue that migrates
onto the cornea
• does not pose a threat to vision
• entirely benign, can be precursors of actinic-
induced neoplasms— squamous cell carcinoma
and melanoma
 Pinguecula
• appears astride the limbus
• small, yellowish submucosal elevation
• does not invade the cornea as pterygium does
• As a consequence of focal dehydration, a
saucer-like depression in the corneal tissue—a
delle—may develop.
 Neoplasms
• squamous neoplasms (preceded by
intraepithelial neoplastic changes)
• Squamous papillomas(t 16/18)
• mucoepidermoid carcinoma of the
conjunctiva(more aggressive)
• melanocytic neoplasms(unilateral)
• Conjunctival nevi-precursor of inflamed
juvenile nevus
 papiloma

Squamous neoplasm

melanoma

nevi

mucoepidermoid
 Blue sclera:
• Bluish-thin after episodes of scleritis
• Increased preassure
• Staphyloma
• osteogenesis imperfecta
• heavily pigmented
• congenital nevus of the underlying uvea-
congenital melanosis oculi
• Periocular nevus of Ota
 Cornea
• The cornea and its overlying tear film—not the
lens—make up the major refractive surface of
the eye
• Myopia- eye is too long for its refractive power
• Hyperopia -an eye that is too short
• Laserassisted in situ keratomileusis (LASIK) to
sculpt the cornea and change its refractive
properties attests to the importance of corneal
shape in contributing to the refractive power
of the eye.
• The corneal stroma lacks blood vessels and
lymphatics:
• contributes to transparency of the cornea
• success of corneal transplantation
• non-immunological graft failure (loss of endothelial
cells/corneal edema) is seen more commonly than
is immunological graft rejection.
• The risk of corneal graft rejection increases with
stromal vascularization and inflammation.
Kayser-Fleischer ring of Wilson disease
 bullous keratopathy
corneal epithelial bullae, resulting from
corneal endothelial disease.
 hypopyon

Corneal ulcer
 Degenerations/dystrophies
• Corneal degenerations(keratopathies) may be
either unilateral or bilateral, nonfamilial.
• corneal dystrophies are typically bilateral and
are hereditary.
• Corneal dystrophies may affect selective
corneal layers
• Calcific band keratopathy-deposition of calcium in
the Bowman layer
• may complicate chronic uveitis, especially in JRA

• Actinic band keratopathy develops in individuals

who are exposed chronically to high levels of
ultraviolet light
 Keratoconus
• progressive thinning and ectasia of the cornea
without evidence of inflammation or
vascularization.
• results in conical rather than spherical cornea
• abnormal shape generates irregular
astigmatism that is difficult to correct with
spectacles
• Associated with:
• Down/Marfan syndrome, atopic disorders.
• corneal hydrops-sudden effusion of aqueous
humor through a gap in the Descemet
membrane.
• An episode of hydrops may be followed by
corneal scarring that can also contribute to
visual loss.
• Acute corneal hydrops can elevate intraocular
pressure in infantile glaucoma (Haab’s striae)
Corneal hydrops glaucoma
 Fuchs endothelial dystrophy
• Stromal edema + bullous keratopathy—are
both related to a primary loss of endothelial
cells.
• endothelial cells produce droplike deposits of
abnormal basement membrane material
(guttata) that resemble the fetal component of
the Descemet membrane ultrastructurally
• Stroma acquires ground-glass appearance
clinically, and vision is blurred
 Stromal dystrophy
• stromal deposits generate discrete opacities in
the cornea may eventually compromise vision.
• may result in painful epithelial erosions.
• Macular corneal dystrophy
• -deposits of keratan sulfate in corneal stroma.
 AD stromal dystrophy(TGFB1)
• lattice dystrophy
• -needle-shaped deposits of
amyloid
• Granular dystrophy -Chunky
deposits of hyalin
• Avelino dystrophy
• -combinations of these two in
same person
 Anterior chamber
• anteriorly -cornea
• laterally - trabecular meshwork
• posteriorly -the iris
• Aqueous humor, formed by ciliary body, enters
posterior chamber, bathes the lens, circulates through
the pupil to gain access to the anterior chamber.
 Cataract
• lenticular opacities that may be congenital or
acquired.
• Causes:
• Systemic diseases (such as galactosemia, diabetes
mellitus, Wilson disease, and atopic dermatitis),
corticosteroids, radiation, trauma
• Agerelated cataract typically results from opacifi
cation of the lens nucleus (nuclear sclerosis).
• accumulation of urochrome pigment may render
the lens nucleus brown, thus distorting the
individual’s perception of blue color
• antigen-antibody complexes containing lens
cortical material develop especially in the
presence of Propionibacterium acnes (which
acts as an adjuvant), generating a lens-induced
uveitis
• lens cortex may liquefy nearly entirely, a
condition known as hypermature or
morgagnian cataract.
• High-molecular-weight proteins from liquefi ed
lens cortex may leak through the lens capsule
(phacolysis).
 Glaucoma
• distinctive changes in the visual field and in the
cup of the optic nerve.
• glaucomas are associated with elevated intra-
ocular pressure or normal p (low-tension
glaucoma)
• aqueous humor is produced in the ciliary body and
passes from the posterior chamber through the pupil
into the anterior chamber.
• drains through the trabecular meshwork, situated in
the angle formed by the intersection between the
corneal periphery and the anterior surface of the iris.
• Classification:
• open-angle glaucoma
• Closed angle glaucoma
 Open angle
• -aqueous humor has complete physical access
to the trabecular meshwork, elevation in intra-
ocular pressure results from an increased
resistance to aqueous outflow in the open
angle
 Close angle glaucoma
• peripheral zone of the iris adheres to the
trabecular meshwork and physically impedes
the egress of aqueous humor from the eye.
Primary angle open Secondary angle open
Most common type high-molecular-weight
lens proteins produced by phacolysis
MYOC gene RBC after trauma (ghost cell glaucoma)
Iris epithelial pigment
granules (pigmentary glaucoma),
fragments of oxytalan
fibers (exfoliation glaucoma
necrotic tumors (melanomalytic
glaucoma
Primary angle closure Secondary angle closure
hyperopia chronic retinal ischemia
Necrotic tumors-retinoblastomas
tumors in the ciliary body
• In intra-ocular inflammation, vessels in the ciliary
body and iris become leaky, allowing cells and
exudate to accumulate in the anterior chamber
• inflammatory cells may adhere to the corneal
endothelium, forming clinically visible keratic
precipitates
• aggregates of macrophages on the endothelium in
sarcoid produce characteristic “mutton-fat” keratic
precipitates.
• exudate in the anterior chamber causes adhesions
between the iris and the trabecular meshwork or
cornea (anterior synechiae) or between the iris and
anterior surface of the lens (posterior synechiae).
• Anterior synechiae can lead to elevation in intra-ocular
pressure, which may lead to optic nerve damage.
Prolonged contact between the iris and the anterior
surface of the lens can deprive lens epithelium of
contact with aqueous humor and can induce fibrous
metaplasia of the lens epithelium: anterior subcapsular
cataract
• suppurative inflammation in the vitreous
humor (endophthalmitis) is poorly tolerated by
the retina;
• Endophthalmitis is classified as exogenous
(originating in the environment and gaining
access to the interior of the eye through a
wound) or endogenous (delivered to the eye
hematogenously)
• panophthalmitis is applied to infl ammation
within the eye that involves the retina,
choroid, and sclera and extends into the orbit
 Uvea
• Uvea-iris, the choroid and ciliary body
• Causes:
• JRA
• Pneumocystis carinii
• Sarcoidosis
• sympathetic ophthalmia
• Retinal toxoplasmosis
• Cytomegalovirus uvitis
 Retina
• Retinal pathology is characterized by
perivascular inflammation; this is responsible
for the well-known ophthalmoscopic sign of
“candle wax drippings.”
• Sympathetic ophthalmia is an example of
noninfectious uveitis limited to the eye. This
condition is characterized by bilateral
granulomatous inflammation typically affecting
all components of the uvea: a panuveitis.
• Uveal melanoma is the most common primary
intra-ocular malignancy of adults.
• Uveal nevi, especially choroidal nevi, are rather
common, affecting an estimated 10% of the
Caucasian population but their progression to
melanoma is exceptionally uncommon.
• Melanomas situated exclusively in the iris tend to
follow a relatively indolent course, whereas
melanomas of the ciliary body and choroid are
more aggressive.