Download - Neuropathology I
Neuropathology I
Main elements of the CNS and their basic pathologic reactions
Neuronsmarked variations in size and shape (Purkinje cell, granular cell)cell body + processes (axon and dendrites)Nissl substance (GER) – proteosynthesis
hypoxic/ischemic injuryshrinkage of the cell body, ↑eosinophilia („red cell change“), pyknosis of the nucleus
axonal injuryswelling 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 atrophyshrinkage of the neuronal body, ↑basophilia, thickened and tortuous („corkscrew“) dendritesneurodegenerative diseases, trans-synaptic degeneration
accumulation of abnormal materiallysosomal disordersinclusions (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 damagegemistocytes (eccentrically expanded pink cytoplasm)
Rosenthal fibresthick, elongated, eosinophilic protein aggregates within astrocytic processeschronic gliosis, low-grade gliomas
corpora amylacearound, basophilic, PAS+ polyglucosan aggregates within end processessubpial, perivascular
Oligodendrocytes
small, round-shaped, dark nucleus in HEmyelin formationregressive changes in demyelinating disorders and leukodystrophy
Ependymal cells
cuboidal lining of the ventricular system
ependymal granulationsependymal damagelocal proliferation of subependymal astrocytes
Choroid plexus
villous structure covered by cuboidal epitheliumstroma contains fenestrated capillariesCSF secretion
cystic degeneration
Microglia
small elongated nucleus in HEbone marrow-derived cells
gitter cellsphagocytosis
rod cellsneurosyphilis
microglial nodules, neuronophagianodules around dying neurons
Cerebral edema, hydrocephalus and intracranial hypertension
Cerebral edemaaccumulation of fluid in excess within cerebral parenchyma
Vasogenic edemaBBB disrupted (haemorrhagia, trauma, tumour) → ↑permeability of vessels → fluid shifted into intercellular spaceslocalized or diffuse
Cytotoxic edemaischaemia → energy failure → disturbance of ionic gradient on cellular membrane → shift of fluid from extracellular to intracellular spaceusually diffuse
macrodiffuse or localized brain swelling, brain softer than normal, flattened gyri, ventricular system compressed
microvacuolation, red cell change, loss of myelin staining, enlargement of extracellular spaces
Hydrocephalusaccumulation of excessive CSF within the ventricles
Normal circulation of CSFproduced by choroid plexus → circulation through ventricular system → exit to subarachnoideal space (foramina Luschka and Magendie) → resorbed by arachnoid granulations
Causesimpaired 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 systemventricular dilatation proximal to the block
Communicating h.reduced CSF resorptiondilatation of the entire ventricular system
Hydrocephalus e vacuocompensatory enlargement of the ventricled due to brain atrophy
macrochildren before the closure of cranial sutures → enlargement of the headadults → 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 hypertensionheadachevomitingpapilloedema (ophthalmoscopy)
Three patterns of brain herniationtranstentorial (uncinate)tonsilarsubfalcine (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 entryhematogeneous spread (most common; endocarditis, bronchiectasia…)local extension from paranasal sinuses, teeth, middle eardirect implantation (trauma, lumbar puncture, ventricular drainage)via peripheral nerves (lyssa, herpetic viruses)
Acute pyogenic meningitisleptomeninges + subarachnoid spaceperivascular spread into underlying brain → meningoencephalitisEtiologyneonates: E. coli, Proteus, Streptococci group Btoddlers + young children: Haemophilus influenzaeadolescents: Neisseria meningitidis (meningococcus)older people: Streptococcus pneumoniae (pneumococcus), Listeria monocytogenesClinical presentationfever, headache, clouding of consciousness, neck stiffneslumbar puncture: ↑pressure, ↑↑neutrophils, ↑protein, ↓glucoseMorphologyleptomeningeal and subarachnoideal purulent exudate over the convexity of brain („pus cap“)Complicationspyocephalusvasculitis → infarctionsarachnoid adhesions → hydrocephalus
Acute viral („aseptic“) meningitis
morbilli, ECHO, Coxsackie, EBV, HSV2
clinical course less severe
macromild brain swelling
micromild lymphocytic infiltration of leptomeninges
lumbar puncture↑lymphocytes, mild ↑protein, glucose normal
Tuberculous meningitisMycobacterium tuberculosishematogeneous spreadrare in developed countries children and young adults
Clinical presentationheadache, malaise, mental confusion, vomitinglumbar puncture: mononuclear cells, protein ↑↑, glucose n. or ↓
Macrobase of the brain (basilary m.)gelatinous exudate within subarachnoid spacewhite nodules
Microlymphocytes, plasma cells, macrophagesepithelioid granulomas with Langhans’ giant cellscaseous necrosisobliterative endarteritis (marked intimal thickening)
Complication: arachnoid fibrosis → hydrocephalus
Brain abscess
acute focal suppurative infectionbacterial infection (Staphylococci, Streptococci)hematogeneous spread (endocarditis, bronchiectasia, osteomyelitis)local extension (sinusitis, middle ear - mastoiditis)direct implantation (trauma)
Clinical presentationfocal neurological deficitssigns of Intracranial hypertension
Morphologysolitary or multiple central liquefactive necrosis + purulent exudatepyogenic membrane (granulation tissue)gliosis, perifocal edema
Complicationspyocephalusherniation
Encephalitisinfection of brain parenchymausually associated with meningitis (meningoencephalitis)
Viral encephalitismost common form of encephalitisplenty of viral agents (measles, herpetic viruses, rabies, CMV, HIV…)common features:
perivascular mononuclear infiltratesmicroglial nodules, neuronophagiainclusion 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
HSV1any age, most common in children and young adultsfrontal and temporal lobes → alterations in mood, memory and behaviorfoci of necrosis and hemorrhageperivasculat inflammatory infiltratesintranuclear inclusions in both neurons and glial cells
HSV2neonates (infection from mother during delivery)severe disseminated encephalitis
Varicella-zoster virusimmunosuppressed patientsacute encephalitis with intranuclear inclusions
Rabies (lyssa)rhabdovirusreservoirs: 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 presentationnonspecific 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
Morphologyswelling and hyperemia of brainslight lymphocytic infiltration of leptomeningesNegri bodies – intracytoplasmatic eosinophilic inclusions (hippocampus, Purkinje cells)
Poliomyelitis acuta anterior
enteroviruseradicated in some countries (Czech rep.), common in developing countriesmost cases: asymptomatic or mild gastroenteritissmall fraction of patients: involvement of motor gray matter
damage and loss of motor neurons of spinal cord and brainstem → flaccid paralysis with muscle atrophymost severe cases: paralysis of respiratory muscles → death from asphyxia
micro:perivascular lymphocytic infiltratesnecrosis of motor neurons → neuronophagia, glial nodules
Human immunodeficiency virus
60% of patients with AIDS develop neurologic dysfunctionseither direct effect of HIV or secondary involvement by opportunistic infections (toxoplasma, cryptococcus, HSV1, HSV2, VZV, CMV, …)
HIV meningoencephalitiscause of AIDS-dementia complexHIV-infected macrophages → cytokines → neuronal damagewidely distributed microglial nodules with multinucleated giant cells
HIV vacuolar myelopathy
HIV polyneuropathy
NeurosyphilisTreponema pallidumthird stage, 10% of untreated patients
Tabes dorsalisdegeneration of posterior spinal columns and roots (sensory fibres) → grayish and shrunkenunsteady and stamping gaitloss of deep tendon reflexesvery severe „lightning“ pains in lower limbssevere degeneration of large joints (Charcot joint)
Progressive paralysis (general paresis of the insane)deterioration of personalitychanges in mental functions (bizzare and grandiose delusions)complete dementiabrain atrophydisorganisation of the cortex (neuronal degeneration, gliosis, perivascular lymphocytic infiltrates, rod cells)
Other encephalitides
Lyme disease (borreliosis)Borrelia burgdorferi, transmitted via tick bitessee musculoskeletal pathology
Fungal encephalitisCandida, Aspergilus, Mucor, Cryptococcusmultiple abscesses, granulomas, hemorrhagic infarcts
ToxoplasmosisToxoplasma gondiiimmunosuppressed individuals, AIDSmultiple foci of necrosis surrounded by mixed inflammatory infiltrationtachyzoites and cyst filled by bradyzoites
Amoebic encephalitisNaegleria: swimming pools, rapidly fatal necrotizing encephalitisAcantamoeba: chronic granulomatous meningoencephalitis
Cysticercosisencysted larvae of tapeworm (Taenia solium)intracranial hypertension (mass effect), seizures
Slow viral infectionsvery long latent period
Subacute sclerosing panencephalitisaltered measles virus or aberrant T-cell response (measles or vaccination in clinical history)adolescentsprogressive loss of intelectual functions, motor abnormalities, dementia, death within 1 yearbrain atrophy, dilatation of ventricles, firm brain tissueloss of neurons, gliosis, subcortical demyelinationintranuclear inclusion bodies within neurons and oligodendrogliaperivascular lymphocytic infiltrations
Progressive multifocal leucoencephalopathyJC virus (member of papovavirus group)preferential infection of oligodendrocytes → demyelinationimmunosupressed individuals (lymphoproliferative disorders, AIDS, immunosuppressive therapy)variable progressive neurologic symptomsmultiple small gray foci throughout the brainloss of myelin staining, reduced number of axons, lipid-laden macrophagesabnormal oligodendrocytes (intranuclear amphophilic inclusions), atypical astrocytes
Prion diseases
abnormal forms of normal cellular protein (prion protein, PrP; prion = proteinaceous infection)abnormal PrP – „knotted“ conformationability of abnormal PrP to initiate comparable conformation changes of other PrP molecules → transmissible diseasesspontaneous conformation change → sporadic formsmutation of gene encoding PrP → higher rate of conformation changes → familial formsaccumulation of abnormal PrP → cell injury (cytoplasmic vacuoles, neuronal cell death
Creutzfeldt-Jacob disease (CJD)rare (incidence 1 per million)in 85% sporadic, some cases familialiatrogenic infections (corneal transplants, human growth hormone preparations, brain implantation electrodes)peak incidence in 7. decade of liferapidly progressive dementia, motor dysfunction, fatal within 1 yearusually no gross abnormalities or mild atrophy (due to rapid course) spongiform transformation of gray mattermultiple small empty vacuoles (intracellular), loss of neurons, reactive gliosis
Variant Creutzfeldt-Jacob disease (vCJD)UK 1995young adults, slower clinical courseexposure to bovine spongiform encephalopathy (BSE, „mad cow disease“)similar histologic picture, abundant cortical amyloid plaques
Gerstmann-Sträussler-Scheinker syndromedementia with cerebellar ataxiaoften familial (autosomal dominant pattern), transmissibleseveral mutations in PrP genemicro similar to CJD + amyloid plaques and amyloidosis of small vessels
Kuruendemic to highlands of New Guinea (Fore tribe)ritual canibalismcerebellar ataxia, progressive motor dysfunction, severe tremor (kuru = shivering)death usually within 1 year