Pathology

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Tuberculosis

Back 1

Chronic bacterial CNS infection typically due to hematogenous spread of bacteria from pulmonary lesions or lymph nodes. Leads to caseous tubercles in the subarachnoid space or brain parenchyma.

Front 2

Common result of discharge of mycobacteria from tubercles into the subarachnoid space

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Chronic tuberculous meningitis that typically affects the base of the brain.

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Microscopic findings of Tuberculous meningitis

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Granulomatous inflammation with multinucleated giant cells, epithelioid cells, macrophages and lymphocytes

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Tuberculoma

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Growth or coalescence of small parenchymal tubercles creates abcesses with a caseous center. It may occur anywhere in the brain, but show a predilection for the cerebellum

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Viral (Aseptic) Meningitis

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Most common viral infection of the CNS

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Common causative agents of viral (aseptic) Meningitis

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Enteroviruses, herpes simplex virus type 2, and mumps virus

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Pathology of Viral (Aseptic) Meningitis

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Mild to moderate lymphocytic infiltration of the leptomeninges.

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Clinical symptoms of Viral (aseptic) Meningitis

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Headache, fever, usually short, bengn course

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Encephalitis

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Viral infections of the brain
Many features of microscopic pathology similar independent of causative virus: Perivascular cuffs of lymphocytes, astrogliosis, microglial nodules, if neurons are infected: neuronophagia.

Viral inclusions in some cases may be characteristic.

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Myelitis

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Viral infections of the spinal cord

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Encephalomyelitis

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Viral infections of the brain and spinal cord

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Clinically most important infections that cause viral encephalitis, myelitis and encephalomyelitis

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HIV, herpes simplex virus, human cytomegalovirus, poliovirus, rabies virus, measles virus, JC virus and arboviruses.

Localizaton of the infection within the CNS is often characteristic for specific viruses.

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HIV Encephalitis

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Infection of CNS leading to opportunistic CNS infections and CNS lymphoma.

-Typically affects deep gray structures and white matter
-Main target cells in CNS are microglial cells.
-Cytokines and reactive oxygen and nitrogen species released from infected cells may cause secondary neuron damage and lead to dementia

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Most common opportunistic CNS infections in AIDS

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CMV encephalitis, toxoplasma abscess, JC virus-induced progressive multifocal leukoencephalopathy

Front 15

Herpes Simplex Encephalitis

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Most common sporadic encephalitis in the US
Affects Immunocompetent people
Most commonly due to HSV-1
Typically involves the temporal lobes

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How does Herpes Simplex Encephalitis Spread

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Initial infection of mucocutaneous surfaces of oral cavity, nose and eye.
Virus infects nerve endings, reaches ganglia in the peripheral nervous system and the CNS by axonal transport, leading to latent infection in most cases.
Initial infection and reactivation from neurons may cause encephalitis.

Front 17

CMV infection of the CNS

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Occurs in fetuses and the immunosupressed
Acute infection leads to necrotizing encehpalitis
Residual lesions causes microcephaly, polymicrogyria, hydrocephalus and periventricular calcifications.

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Target of CMV ventriculoencephalitis in AIDS patients

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Ependyma and subependymal brain parenchyma

Front 19

Fungal infections of the CNS

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Affect primarily immunocompromised patients in industrialized countries
Presents as a component of widespread hematogenous dissemination of fungus

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3 patterns of Fungal infections of the CNS

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Vasculitis, chronic meningitis and parenchymal invasion (granulomas or abscesses)

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Causative agent of Fungal infections of the CNS

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Mucormycosis: CNS vasculitis following local brain invasion from a paranasal sinus in a DKA patient.

Others include: Aspergillus and Candida

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Fungi causing chronic meningitis

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Histoplasma capsulatum, Coccidioides immitis, blastomyces dermatitidis, Cryptococcus neoformans

Cryptococcal meningitis: common in AIDS patients

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Cryptococcus meningitis

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Fungi that cause chronic meningitis. Presents as multiple small cysts in the basal ganglia corresponding to aggregates of fungi within expanded perivascular spaces with minimal associated inflammation.

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Toxoplasmosis

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Protozoal CNS Infection
Important cause of congenital infection (like CMV)
Causes solitary or multifocal abscesses in the immunocompromised. Cysts can have bradyzoites.
Up to 30% of AIDS patients affected

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Classic triad of congenital toxoplasma infection

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Cerebral calcification
Hydrocephalus
Chorioretinitis

Front 26

Two major categories of diseases of myelin

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1. Leukodystrophies: Associated with abnormal myelin metabolism

2. Demyelinating diseases: Associated with loss of normal myelin. Most common: Multiple sclerosis

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Leukodystrophies

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Disease of Myelin that include inherited diseases that typically onset in infancy to adolescense with diffuse white matter involvement and a relentless progressive course.

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Multiple sclerosis characteristics

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Sporadic incidence, typical onset in the 20's and 30's, multiple demyelinating foci and different times during disease course, waxing and waning course.

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Metachromatic Leukodystrophy

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Most common leukodystrophy
-Intra and extracellular deposition of metachromatic -sulfatides
-arylsulfatase A deficiency
-autosomal recessive inheritance

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Gross pathology of Multiple sclerosis

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Multiple, well delineated, firm, gray lesions (plaques) in white matter, may focally extend into gray matter

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Microscopic pathology of Multiple sclerosis

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Well defined area of selective myelin loss with relative preservation of axons.

Lymphocytic infiltrate, loss of oligodendrocytes, foamy macrophages, astrogliosis

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Clinical/common symptoms of Multiple Sclerosis

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Clinical-Distinct episodes of neurological deficits attributable to white matter lesions "separated in time and space", waxing and waning course.

Symptoms- impaired vision, motor weakness, paresthesias, ataxia, etc.

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Multiple Sclerosis etiology

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Prevalence: 1:1000 in US
Autoimmune demyelinating disease
Genetic Influence: Associated w/HLA antigens; incidence 150-folds higher with affected monozygotic twins
Environmental agents, like viruses, may have a role in initiating autoimmune reaction.

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Acute Pyrogenic Bacterial Meningitis

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Bacterial reach leptomeninges by hematogenous or local extension routes resulting in neutrophilic leptomeningeal infiltrate. Can be associated with vasculitis and thrombosis of leptomeningeal vessels resulting in multifocal infarction of brain parenchyma.

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Symptoms of Acute pyogenic bacterial meningitis

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Headache, fever, cervical rigidity, delirium, coma

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Most common cause of acute pyogenic meningitis in neonates

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E.coli, group B streptococcus

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Most common cause of Acute pyogenic meningitis in young children

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Streptococcus pneumoniae

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Most common cause of Acute pyogenic meningitis in young adults

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Neisseria meningitidis (meningococcus)

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Most common cause of acute pyogenic meningitis later in life

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Streptococcus pneumoniae (pneumoncoccus)

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Predisposing conditions to brain abscess

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Acute bacterial endocarditis
Chronic pulmonary sepsis
Immunosupppression

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Most common cause of brain abscess in immunocompentent patients

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Staphylococcic and streptococci

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Preferential site of brain abscesses

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Gray/white junction

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Most important route bacteria reach brain parenchyma in the formation of brain abscesses

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Hematogenous route

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Main determinants of clinicopathologic presentation in CNS infections

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Microbial virulence
Dose and route of CNS entry
Host immune status and age

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What do the main determinants of clinicopathologic presentation of CNS infections?

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Disease course
Disease site
Associated tissue reaction

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CNS findings of an acute pyogenic bacteria meningitis

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Neutrophil infitration
High Protein
Low glucose

Front 47

How does Acute pyogenic bacterial meningits in patients?

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Parenchyma damage due to infarction because vessels in the meningies are injured during the process

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Why is the gray/white junction a preferential site for brain abscess?

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Vessels will show a narrowing as they leave the gray matter and enter the white matter. Any type of embolus will most likely get stuck in this area i.e. metastatic carcinomas, septic embolus coming from the heart or lungs.

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What is special about the abscesses that from in the brain?

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They have a fibrous capsule around it that's formed from fibroblast from surrounding vessels.

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Complication of brain abscess

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If the fibrous and/or glial response is not strong enough to limit the injury, you can a rupture. This can result in a secondary abscess that goes to the ventricular system. Because this is a space occupying lesion, you can get a herniation that can lead to death

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Differential between the gross pathology of Acute and Chronic meningitis

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Acute meningitis- The purulent often goes to the hemispheric surface in addition the base of the brain

Chronic meningitis- tends to primary involve the basal layers of the brain.

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CSF findings of TB (chronic) meningitis

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Primary PMN infiltrate with neutrophils present
Extremely high protein levels
Normal or slightly decrease glucose levels

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CSF finding in viral meningitis

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Lymphocytic (PMN) infiltrate
Slightly increase protein levels
Normal glucose levels

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Localization of patient with CNS infection due to the poliovirus

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Motor symptoms involvement of the anterior horns of the spinal cord

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Localization of CNS infection due to Herpes

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Limbic encephalitis involving the temporal lobes of the brain

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Localization of patient with CNS infection due to CMV

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Perivascular

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Common features of viral encephalitis

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Combination of parenchyma and meningeal involvement
Parivascular cuffs- mononuclear infiltrate around vessels
Microglia response leading to microglial nodule formation
Neuronphagia- dying neuron surrounded by phagocytic cells
Astrogliosis

Front 58

Differentiate between Viral Encephalitis caused by HIV and CMV

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HIV Encephalitis causes HIV targets microglial cells resulting in multinucleated giant cells in the brain. Typically affects deep gray structures and white matter. Neurons and other glial cells are spared, but can be damaged secondary due cytokines and reactive oxygen and nitrogen species released from infected microglial. This can lead to HIV dementia.

CMV- will cause non-multinucleated giant cells in the brain. Infections will be localized to paraventricular area. Grossly, the brain will have hemorrhagic limic encephalitis in the bilateral temporal lobe, orbitofrontal cortex on the visceral surface of the brain. Targets include ependyma and subependymal brain parenchyma.

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What gross pathology does CMV share with toxoplasma, herpes and rubella infections of the CNS?

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Small Brain often with developmental abnormalities.
Problems with formation of the brain and the presence of calcification.
Ventricularmegaly hydrocephalus

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Pathogenesis of MUrcomycosis infection of the CNS

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Diabetic patient with DKA. Hemorrhage is in the orbitofrontal reigions of the brain b/c the fungus colonizes the sinuses and spreads through the cribiform plate through the vessels and into the brain.

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Typical patient infected with aspergillosis of the CNS and classic pathology

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Immunosupressed patient that has multiple hemorrhagic foci in the brain. There's no localization, diffrent portions of the brain will be involved. Tends to infect the large vessels causing large hemorrhages in the brain

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What size vessels does candida infect?

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Smaller vessels, resulting in smaller hemorrhages

Front 63

Describe the appearance of cryptococcus meningitis infection

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In immunocomprised patients, cyrpto-spores can fill up the perivascular spaces. There will be little to no inflammation. As the perivascular space expand they will take on a soap bubble appearance.