CNS Histology and Pathology of Infection Flashcards
Name the components of the covering of the CNS and identify their relationships, including layers and spaces.
- Dura: thick, tough outer layer
- Arachnoid: looser cellular layer with projections into underlying pia and granulations
- Pia: thin layer attached to brain which anchors strands of arachnoid trabeculae
- Epidural space: not present in brain because dura is attached to skull
- Subdural space: potential space where blood can collect after injury
- Subarachnoid space: contains CSF
- Virchow-Robin space: the part of the subarachnoid space that follows vessels into the brain parenchyma
What are arachnoid granulations?
Arachnoid granulations occupy the dural sinuses that arise from layers of the dura and absorb CSF to send it back into circulation. They can calcify with age but this is not necessarily pathological.
Describe the morphology of neurons. How are they arranged in the CNS?
Neurons contain dendrites, a cell body, and an axon and exhibit variability in size and shape. Most are multipolar and have a large central nucleus and a large nucleolus. They also contain Nissl substance (active rough ER) in the cell body.
Neurons are organized in various ways to perform different functions in the CNS.
How are neurons in the neocortex organized?
The neocortex contains six layers that vary depending on the function of that part of the neocortex.
- Molecular layer
- External granular layer
- External pyramidal layer
- Internal granular layer
- Internal pyramidal layer
- Plexiform layer
How are neurons in the hippocampus organized?
Hippocampal cortex is referred to as an archicortex and is composed of four regions based on the cytoarchitecture of the single layer of pyramidal cells which comprise it and their interconnections.
How are neurons in the cerebellar cortex organized?
The cerebellar cortex is organized into three layers:
- Molecular layer: contains processes
- Purkinje layer: contains large cells which project into the molecular layer
- Granule layer: contains small cells
Describe the histological appearance of astrocytes and oligodendrocytes.
Astrocytes are located in both white and gray matter and their processes are not easily visible in sections. They appear to be bare nuclei.
Oligodendrocytes are much larger, contain cytoplasm, and have densely hyperchromatic nuclei.
Describe the functional significance of astrocytes and oligodendrocytes.
Astrocytes extend foot processes around the basement membranes of blood vessels so they are important structurally. They also mediate metabolic exchange between neurons and the blood.
Oligodendrocytes are responsible for myelinating neuronal processes in the CNS. They are likely involved in both structural and metabolic support.
What are ependymal cells? What are choroid plexus cells?
Ependymal cells are cuboidal and line the ventricles of the brain and the central canal. They are glial derived but form an epithelial-like layer with villi. They can have elongated processes that link the ventricular, vascular, and intraparenchymal compartments of the CSF by extending into the subependymal vasculature.
The choroid plexus cells make up projections of vascular stroma derived from the meninges and are responsible for secreting CSF.
Describe the ways neurons respond to injury.
- Acute ischemic injury: produces “red neurons” with small pycnotic nucleus
- Chronic injury: results in cell death and loss
- Neuronal inclusions: lipofushin accumulations along the perikaryal edge, cytoplasmic flame shaped inclusions (neurofibrillary tangles), intranuclear and cytoplasmic viral inclusions, cytoplasmic round inclusions (Lewy bodies)
How do glial cells respond to injury?
Glial cells undergo gliosis. Astrocytes are the main effectors of reaction to injury in the CNS through both hypertrophy and hyperplasia.
What are the inflammatory infiltrates in the CNS?
- Neutrophils (acute)
- Mononuclear cells (chronic), specifically microglia which react to injury by hyperplasia and becoming elongated
- Granulomatous inflammation
What are the four ways that infectious organisms access the CNS?
- Hematogenous spread if it can cross BBB
- Local extension (severe infection of paranasal sinuses or middle ear)
- Retrograde transport from PNS
- Direct implantation (injury, surgery)
What predisposing factors interfere with normal defense mechanisms?
- Immunosuppression
- Mechanical devices/surgical interventions
- Anatomical congenital malformations
- Hyposplenism and asplenia
Define:
- Pachymeningitis
- Meningitis/leptomeningitis
- Encephalitis
- Cerebritis
- Pachymeningitis: spread of infection into the dura mater
- Meningitis/leptomeningitis: inflammation of pia and arachnoid
- Encephalitis: inflammation of brain parenchyma with mononuclear cells (typically viral)
- Cerebritis: inflammation of the brain parenchyma with neutrophils (typically bacterial)
Define:
- Myelitis
- Poliomyelitis
- Ganglionitis
- Radiculitis
- Myelitis: inflammation of the spinal cord
- Poliomyelitis: inflammation of the spinal gray matter
- Ganglionitis: inflammation of the dorsal root ganglion
- Radiculitis: inflammation of the intradural spinal nerve roots
What are the different types of inflammatory infiltrates? What etiologic organisms are they associated with?
- Neutrophils: acute inflammation due to bacterial meningitis, cerebritis, or abscess
- Mononuclear cells: lymphocytes and plasma cells associated with chronic inflammation due to viral meningitis or encephalitis
- Granulomatous inflammation: due to mycobacteria, spirochetes, fungi, or parasites
- Microglial nodules: viral encephalitis
What does the image below represent? In what cerebral spaces can this infection occur? What organisms cause it and what cells respond to it?
Acute bacterial meningitis
- Epidural space (abscess)
- Subdural space (abscess or empyema)
- Subarachnoid space (meningitis)
- Parenchyma (abscess or cerebritis)
Caused by:
- S. pneumoniae
- N. meningiditis
- H. influenzae
Presents with neutrophils in leptomeningeal space
What does the image below represent? What is the source of this infection? What organisms cause it? How is the CNS affected?
Bacterial abscess due to a mass forming acute infection
Source:
- Local (sinusitis otitis or mastoiditis)
- Hematogenous (septic emboli from bacterial endocarditis)
Caused by:
- S. aureus
- Streptococci
Presents witih:
- Lesions with liquefactive necrosis surrounded by a fibrotic capsule
- Mass effect can cause herniation
- Vascular congestion, necrosis, edema, inflammation with neutrophils early on
- Late findings involve lymphocytes, macrophages, and granulation tissue
How does tuberculosis meningitis present?
Tuberculosis meningitis is the most common form of mycobacterial infection and involves the basal aspect of the brain with cranial nerve involvement.
Characterized by necrotizing granulomas, lymphocytes, multinucleated giant cells, and fibrosis.
What is neuroborreliosis? What causes it? How does it present?
Lyme disease is caused by Borrelia burgdorferi
Presents with:
- Aseptic lymphocytic meningitis
- Facial nerve palsy
- Neuropathies/polyradiculitis
- Encephalopathy
Describe the unique features of herpetic encephalitis (HSV-1). CMV encephalitis? VZV encephalitis?
Herpetic encephalitis (HSV-1):
- Bilateral, asymmetrical hemorrhagic necrosis of temporal lobes
- Presents with features of encephalitis and focal neurological signs
CMV encephalitis:
- Significant only congenitally and in immunosuppressed patients
VZV encephalitis:
- Rare with varicella, may occur in immuno-suppressed zoster patients
What does this image show? What disease is this a classical histological feature of?
Negri bodies are sharply delineated round to oval eosinophilic inclusions present in neuronal cytoplasm in patients infected with rabies.
Which fungus is this? Describe its pattern of infiltration and microscopic presentation.
Aspergillus
- Disseminates hematologically and fungal hyphae infiltrate blood vessels
- Causes vascular thrombosis, hemorrhage, and infarctions–fibrous capsules rarely form
Which fungus is shown below? How is it different from Aspergillus? How does it spread to the CNS and how does it present?
Mucor (zygomycosis or mucormycosis) is similar to aspergillus but hyphae are wider and non-septate
Spread:
- Rhinocerebral
- Hematological
Presentation:
- Early: facial swelling and hyperemia, ulceration or necrosis of skin/mucosa, orbital symptoms, headaches, nuchal rigidity
- Late: Seizures, aphasia, hemiplegia, lethargy, disorientation, coma, death
Describe amebic encephalitis clinically and histologically.
Organism: Naegleria fowleri is aquired by swimming in warm fresh water than contains the amebae
Presentation:
- Fulminant, acute meningoencephalitis
- Cerebral swelling
- Hemorrhagic necrosis of frontal and olfactory bulbs
Histology:
- Unicellular organism in subarachnoid space (looks like macrophage)
Describe cysticercosis.
Infection with cysticerci (larvae of tapeworm Taenia solium) is the most common helminthic CNS disease.
Presents with parenchymal, meningeal, ventricular, and (rarely) spinal corde cysts.
What infections is represented below? Describe the pathology.
Cryptococcal meningitis (Cryptococcus neoformans) is the most common fungal infection of the CNS. Clinical presentation is variable.
Pathology:
- Minimal inflammatory reaction with lymphocytes, plasma cells, eosinophils, and mutlinucleated giant cells
- Collections of organisms produce gelatinous pseudocystic dilations of Virchow-Robin spaces
What disease classically presents with the histology below?
HIV Encephalitis: involves subcortical white matter, basal ganglia, and brainstem
Pathology:
- Multinucleated giant cells
- Leukoencephalopathy with patchy demyelination and gliosis
- Low grade inflammation with perivascular and parencymal lymphocytes and microglial nodules
Describe the pathology of progressive multifocal leukoencephalopathy.
JC Virus infects oligodendrocytes preferentially
Pathology:
- Ill defined demyelinating lesions
- Lipid laden macrophages
- Intranuclear viral inclusions
- Bizarre astrocytes
What is the difference between the blood-brain barrier and the blood-CSF barrier?
There are two routes of entry into the CNS: via the capillaries of the brain or through the blood supply to the choroid plexus. The capillaries of the blood brain barrier have tight junctions between non-fenestrated capillaries and endothelial cell, a thick basement membrane, and astrocyte endfeet to prevent entry of most molecules. Large charged molecules are excluded while lipid soluble molecules readily cross.
The blood-CSF barrier involves the selective transport of molecule from the ultrafiltrate into the CSF by choroid cells.
