Transcript neuropathology01web

Neuropathology I
Main elements of the CNS and their basic
pathologic reactions
Neurons
marked variations in size and shape (Purkinje cell, granular cell)
cell body + processes (axon and dendrites)
Nissl substance (GER) – proteosynthesis
hypoxic/ischemic injury
shrinkage of the cell body, ↑eosinophilia („red cell change“), pyknosis of the
nucleus
axonal injury
swelling and rounding of the neuronal body, central chromatolysis
(disappearance of the Nissl substance)
axonal spheroids (disruption of axonal transport), Waller degeneration distally
from the site of injury
neuronal atrophy
shrinkage of the neuronal body, ↑basophilia, thickened and tortuous („corkscrew“)
dendrites
neurodegenerative diseases, trans-synaptic degeneration
accumulation of abnormal material
lysosomal disorders
inclusions (viral, neurodegenerative diseases)
Astrocytes
oval-shaped pale nucleus, numerous processes (invisible in HE)
supporting and metabolic function
gliosis (hypertrophy and hyperplasia)
repair of brain tissue damage
gemistocytes (eccentrically expanded pink cytoplasm)
Rosenthal fibres
thick, elongated, eosinophilic protein aggregates within astrocytic processes
chronic gliosis, low-grade gliomas
corpora amylacea
round, basophilic, PAS+ polyglucosan aggregates within end processes
subpial, perivascular
Oligodendrocytes
small, round-shaped, dark nucleus in HE
myelin formation
regressive changes in demyelinating disorders and leukodystrophy
Ependymal cells
cuboidal lining of the ventricular system
ependymal granulations
ependymal damage
local proliferation of subependymal astrocytes
Choroid plexus
villous structure covered by cuboidal epithelium
stroma contains fenestrated capillaries
CSF secretion
cystic degeneration
Microglia
small elongated nucleus in HE
bone marrow-derived cells
gitter cells
phagocytosis
rod cells
neurosyphilis
microglial nodules, neuronophagia
nodules around dying neurons
Cerebral edema, hydrocephalus and
intracranial hypertension
Cerebral edema
accumulation of fluid in excess within cerebral parenchyma
Vasogenic edema
BBB disrupted (haemorrhagia, trauma, tumour) → ↑permeability of vessels →
fluid shifted into intercellular spaces
localized or diffuse
Cytotoxic edema
ischaemia → energy failure → disturbance of ionic gradient on cellular
membrane → shift of fluid from extracellular to intracellular space
usually diffuse
macro
diffuse or localized brain swelling, brain softer than normal, flattened gyri,
ventricular system compressed
micro
vacuolation, red cell change, loss of myelin staining, enlargement of extracellular
spaces
Hydrocephalus
accumulation of excessive CSF within the ventricles
Normal circulation of CSF
produced by choroid plexus → circulation through ventricular system → exit to
subarachnoideal space (foramina Luschka and Magendie) → resorbed by
arachnoid granulations
Causes
impaired flow of CSF (subarachnoideal scarring after meningitis or hematoma,
block of ventricular system by tumour or blood clot, congenital malformations)
↓resorption of CSF (hypoplasia or damage of arachnoideal granulations)
↑secretion of CSF (choroid plexus tumours)
Noncommunicating h.
CSF flow block within ventricular system
ventricular dilatation proximal to the block
Communicating h.
reduced CSF resorption
dilatation of the entire ventricular system
Hydrocephalus e vacuo
compensatory enlargement of the ventricled due to brain atrophy
macro
children before the closure of cranial sutures → enlargement of the head
adults → dilatation of the ventricular system, intracranial hypertension
Intracranial hypertension
brain enclosed within rigid container (skull)
↑volume of intracranial contents (edema, hydrocephalus, tumour, haemorrhage,
abscess…) → ↑intracranial pressure → displacement of brain tissue across dural
barriers or through openings (herniation), decrease of blood perfusion (global
ischaemia)
General clinical features of intracranial hypertension
headache
vomiting
papilloedema (ophthalmoscopy)
Three patterns of brain herniation
transtentorial (uncinate)
tonsilar
subfalcine (cingulate)
Transtentorial (uncinate) herniation
medial aspect of temporal lobe compressed against margin of tentorium
damage of III. cranial nerve → pupillary dilation and impairment of ocular
movements on the side of the lesion
compression of posterior cerebral artery → ischemia of occipital lobe (including
primary visual cortex)
tearing of penetrating vessels → Duret’s hemorage of midbrain and pons
Tonsilar herniation
cerebelar tonsils into foramen magnum
brainstem compresion → damage of respiratory and cardiac centres of medulla
Subfalcine (cingulate) herniation
cingulate gyrus under the edge of falx
compression of anterior cerebral artery → infarction
Infections
Infections
Possible routes of entry
hematogeneous spread (most common; endocarditis, bronchiectasia…)
local extension from paranasal sinuses, teeth, middle ear
direct implantation (trauma, lumbar puncture, ventricular drainage)
via peripheral nerves (lyssa, herpetic viruses)
Acute pyogenic meningitis
leptomeninges + subarachnoid space
perivascular spread into underlying brain → meningoencephalitis
Etiology
neonates: E. coli, Proteus, Streptococci group B
toddlers + young children: Haemophilus influenzae
adolescents: Neisseria meningitidis (meningococcus)
older people: Streptococcus pneumoniae (pneumococcus), Listeria
monocytogenes
Clinical presentation
fever, headache, clouding of consciousness, neck stiffnes
lumbar puncture: ↑pressure, ↑↑neutrophils, ↑protein, ↓glucose
Morphology
leptomeningeal and subarachnoideal purulent exudate over the convexity of brain
(„pus cap“)
Complications
pyocephalus
vasculitis → infarctions
arachnoid adhesions → hydrocephalus
Acute viral („aseptic“) meningitis
morbilli, ECHO, Coxsackie, EBV, HSV2
clinical course less severe
macro
mild brain swelling
micro
mild lymphocytic infiltration of leptomeninges
lumbar puncture
↑lymphocytes, mild ↑protein, glucose normal
Tuberculous meningitis
Mycobacterium tuberculosis
hematogeneous spread
rare in developed countries
children and young adults
Clinical presentation
headache, malaise, mental confusion, vomiting
lumbar puncture: mononuclear cells, protein ↑↑, glucose n. or ↓
Macro
base of the brain (basilary m.)
gelatinous exudate within subarachnoid space
white nodules
Micro
lymphocytes, plasma cells, macrophages
epithelioid granulomas with Langhans’ giant cells
caseous necrosis
obliterative endarteritis (marked intimal thickening)
Complication: arachnoid fibrosis → hydrocephalus
Brain abscess
acute focal suppurative infection
bacterial infection (Staphylococci, Streptococci)
hematogeneous spread (endocarditis, bronchiectasia, osteomyelitis)
local extension (sinusitis, middle ear - mastoiditis)
direct implantation (trauma)
Clinical presentation
focal neurological deficits
signs of Intracranial hypertension
Morphology
solitary or multiple
central liquefactive necrosis + purulent exudate
pyogenic membrane (granulation tissue)
gliosis, perifocal edema
Complications
pyocephalus
herniation
Encephalitis
infection of brain parenchyma
usually associated with meningitis (meningoencephalitis)
Viral encephalitis
most common form of encephalitis
plenty of viral agents (measles, herpetic viruses, rabies, CMV, HIV…)
common features:
perivascular mononuclear infiltrates
microglial nodules, neuronophagia
inclusion bodies
Tick encephalitis
arboviruses (arthropod borne)
several forms (central european, russian, St. Louis fever, …)
transmitted by tick bites, disease reservoirs – animals (rodents)
perivascular monocelular infiltrates, lymphocytic meningitis
severe cases: focal gray and white matter necroses, individual neuronal necrosis
followed by neuronophagia and glial nodules → neurologic deficits (paresis)
Herpetic encephalitis
HSV1
any age, most common in children and young adults
frontal and temporal lobes → alterations in mood, memory and behavior
foci of necrosis and hemorrhage
perivasculat inflammatory infiltrates
intranuclear inclusions in both neurons and glial cells
HSV2
neonates (infection from mother during delivery)
severe disseminated encephalitis
Varicella-zoster virus
immunosuppressed patients
acute encephalitis with intranuclear inclusions
Rabies (lyssa)
rhabdovirus
reservoirs: various animals (dogs, foxes, bats)
transmission by bite of a rabid animal (saliva)
virus enters CNS by ascending along peripheral nerves → incubation period up
to 9 months
Clinical presentation
nonspecific symptoms (malaise, fever, headache)
severe CNS excitability (even slight touch → convulsions)
hydrophobia (painful pharyngeal contracture after swallowing or even looking at
water)
death from respiratory center failure
Morphology
swelling and hyperemia of brain
slight lymphocytic infiltration of leptomeninges
Negri bodies – intracytoplasmatic eosinophilic inclusions (hippocampus,
Purkinje cells)
Poliomyelitis acuta anterior
enterovirus
eradicated in some countries (Czech rep.), common in developing countries
most cases: asymptomatic or mild gastroenteritis
small fraction of patients: involvement of motor gray matter
damage and loss of motor neurons of spinal cord and brainstem → flaccid
paralysis with muscle atrophy
most severe cases: paralysis of respiratory muscles → death from asphyxia
micro:
perivascular lymphocytic infiltrates
necrosis of motor neurons → neuronophagia, glial nodules
Human immunodeficiency virus
60% of patients with AIDS develop neurologic dysfunctions
either direct effect of HIV or secondary involvement by opportunistic infections
(toxoplasma, cryptococcus, HSV1, HSV2, VZV, CMV, …)
HIV meningoencephalitis
cause of AIDS-dementia complex
HIV-infected macrophages → cytokines → neuronal damage
widely distributed microglial nodules with multinucleated giant cells
HIV vacuolar myelopathy
HIV polyneuropathy
Neurosyphilis
Treponema pallidum
third stage, 10% of untreated patients
Tabes dorsalis
degeneration of posterior spinal columns and roots (sensory fibres) → grayish and
shrunken
unsteady and stamping gait
loss of deep tendon reflexes
very severe „lightning“ pains in lower limbs
severe degeneration of large joints (Charcot joint)
Progressive paralysis (general paresis of the insane)
deterioration of personality
changes in mental functions (bizzare and grandiose delusions)
complete dementia
brain atrophy
disorganisation of the cortex (neuronal degeneration, gliosis, perivascular
lymphocytic infiltrates, rod cells)
Other encephalitides
Lyme disease (borreliosis)
Borrelia burgdorferi, transmitted via tick bites
see musculoskeletal pathology
Fungal encephalitis
Candida, Aspergilus, Mucor, Cryptococcus
multiple abscesses, granulomas, hemorrhagic infarcts
Toxoplasmosis
Toxoplasma gondii
immunosuppressed individuals, AIDS
multiple foci of necrosis surrounded by mixed inflammatory infiltration
tachyzoites and cyst filled by bradyzoites
Amoebic encephalitis
Naegleria: swimming pools, rapidly fatal necrotizing encephalitis
Acantamoeba: chronic granulomatous meningoencephalitis
Cysticercosis
encysted larvae of tapeworm (Taenia solium)
intracranial hypertension (mass effect), seizures
Slow viral infections
very long latent period
Subacute sclerosing panencephalitis
altered measles virus or aberrant T-cell response (measles or vaccination in
clinical history)
adolescents
progressive loss of intelectual functions, motor abnormalities, dementia, death
within 1 year
brain atrophy, dilatation of ventricles, firm brain tissue
loss of neurons, gliosis, subcortical demyelination
intranuclear inclusion bodies within neurons and oligodendroglia
perivascular lymphocytic infiltrations
Progressive multifocal leucoencephalopathy
JC virus (member of papovavirus group)
preferential infection of oligodendrocytes → demyelination
immunosupressed individuals (lymphoproliferative disorders, AIDS,
immunosuppressive therapy)
variable progressive neurologic symptoms
multiple small gray foci throughout the brain
loss of myelin staining, reduced number of axons, lipid-laden macrophages
abnormal oligodendrocytes (intranuclear amphophilic inclusions), atypical
astrocytes
Prion diseases
abnormal forms of normal cellular protein (prion protein, PrP; prion =
proteinaceous infection)
abnormal PrP – „knotted“ conformation
ability of abnormal PrP to initiate comparable conformation changes of other PrP
molecules → transmissible diseases
spontaneous conformation change → sporadic forms
mutation of gene encoding PrP → higher rate of conformation changes → familial
forms
accumulation of abnormal PrP → cell injury (cytoplasmic vacuoles, neuronal cell
death
Creutzfeldt-Jacob disease (CJD)
rare (incidence 1 per million)
in 85% sporadic, some cases familial
iatrogenic infections (corneal transplants, human growth hormone preparations, brain
implantation electrodes)
peak incidence in 7. decade of life
rapidly progressive dementia, motor dysfunction, fatal within 1 year
usually no gross abnormalities or mild atrophy (due to rapid course)
spongiform transformation of gray matter
multiple small empty vacuoles (intracellular), loss of neurons, reactive gliosis
Variant Creutzfeldt-Jacob disease (vCJD)
UK 1995
young adults, slower clinical course
exposure to bovine spongiform encephalopathy (BSE, „mad cow disease“)
similar histologic picture, abundant cortical amyloid plaques
Gerstmann-Sträussler-Scheinker syndrome
dementia with cerebellar ataxia
often familial (autosomal dominant pattern), transmissible
several mutations in PrP gene
micro similar to CJD + amyloid plaques and amyloidosis of small vessels
Kuru
endemic to highlands of New Guinea (Fore tribe)
ritual canibalism
cerebellar ataxia, progressive motor dysfunction, severe tremor (kuru =
shivering)
death usually within 1 year