CNS Pathology

Terminology

• Schwann cells

• Astrocytes

• Oligodendrocyte

• Ependymal cells

• Microglia

• Schwann cells: form myelin sheaths in the PNS

• Astrocytes: have end-feet and wrap around blood vessels to create BBB

• Oligodendrocyte: create myelin sheath in CNS

• Ependymal cells: produce CSF and help it circulate

• Microglia: CNS macrophage

Reactions of Neurons to Injury

• Acute Hypoxia/Ischemia

• Axonal Injury

• Intracellular Inclusions

Reactions of Neurons to Injury

• Acute Hypoxia/Ischemia: the cell body will shrink (nuclear pyknosis), causing a “red neuron”

• Axonal Injury: the cell body will swell and the nuclei enlarges, thus the cytoplasm becomes “pale” (central chromatolysis)

• Intracellular Inclusions: aggregated proteins

Reactions of Astrocytes to Injury

• Gemistocytic astrocytes

• Astrogliosis

• Chronic Gliosis

Reactions of Microglial Cells to Injury

Reactions of Oligodendrocytes and ependymal Cells to Injury

Reactions of Astrocytes to Injury

• Gemistocytic astrocytes: swollen eosinophilic cytoplasm with branching processes

• Astrogliosis: abnormal increase in the number of astrocytes

• Chronic Gliosis: may have protein aggregates presenting as “rosenthal fibers”

  Reactions of Microglial Cells to Injury

  • Proliferation, Elongated nuclei, cell aggregates

    Reactions of Oligodendrocytes and ependymal Cells to Injury

  • LImited

How do Intracranial Space-Occupying Lesions cause injury?

• Name some of these diseases

• They cause brain volume expansion, thus increased intracranial pressure, thus decreased brain perfusion and hypoxic brain areas which will lead to mild neurological deficits to death

  • Cerebral edema

  • Hydrocephalus

  • Intracranial Herniatioj

Describe the 3 types of Intracranial space-occupying lesions

• Cerebral edema

  • Vasogenic edema: BBB integrity is broken and fluid shifts into the extravascular space, gyri look flattened

  • Cytotoxic edema: increased INTRAcellular fluid

    

• Hydrocephalus

  • Non-communicating: results from impaired flow of CSF between ventricles and subarachnoid space

    

  • Communicating: arachnoid villi are damaged so resorption of CSF is impaired, thus the entire ventricular system is enlarged

    

• Intercranial Herniation: displacement of brain tissue from one compartment to the other

  • Subfalcine: expansion of cingulate gyrus under falx cerebri

    • Often clinically silent and harmless

  • Transtentorial: expansion of medial part of temporal lobe through tentorial opening

    • 3rd cranial nerve compression thus pupillary dilation and ocular movement impaired

    • Ischemic injury of tissue, hemiparesis

  • Tonsillar: displacement of cerebellar tonsils through foramen magnum

    • Most severe; can lad to cardiorespiratory failure and is often fatal

Cerebrovascular disease leading to ISCHEMIA

• Types

  • Define

  • Consequences

  • Gross and Histopathological changes

• Global Cerebral Ischemia: generalized ischemia usually due to cardiopulmonary arrest or severe systemic hypotension

  • Consequences

    • If transient, full recovery is possible

    • If long, severe neurological impairment with persistent vegetative state can occur OR brain death

  • Gross and Histopathological changes

    • Swollen brain with poor definition between gray and white matter

    • Red neurons and wedge shaped/ watershed infarct zones

      

• Focal Cerebral Ischemia: infarction is only in the brain area supplied by the artery that is occluded

  • Consequences

    • In situ thrombosis, embolism or thromboembolism

  • Gross and Histopathological changes

    • Pale, soft, swollen

    • Red neurons, neutrophilic infiltration

    • Cystic infarct (empty cavity results after months

    • Then gelatinous and friable then liquefaction present

      

Cerebrovascular diseases due to Hemorrhage

• Define

• Consequences

• Gross and Histopathological changes

• Intracerebral Hemorrhage: occurs in 60yo and typically affects the basal ganglia, brainstem, cerebellum and cerebral cortex

  • Consequences

    • Caused by systemic hypertension and leads to mild damage/silent in small areas but can be lethal if in large areas or extension to ventricles

  • Gross and Histopathological changes

    • Can be gradually resolved if small

    • Brown cavity with discolored rim

      

• Subarachnoid space: usually occurs due to saccular/berry aneurysms occurring in branching of arteries

  • Consequences:

    • Intracranial pressure dramatically increases

    • When ruptured, a sudden “thunderclap headache” and loss of consciousness occurs

      

Parenchymal Injuries due to Trauma

• Define

• Consequences

• Gross and Histopathological changes

• Brain Concussion: Widespread brain trauma

  • Consequences:

    • Transient loss of consciousness, non-lethal

  • Gross and Histopathological changes: none

• Brain Contusion: Local trauma t brain tissue

  • Consequences:

    • Minor swelling/bruising, dizziness, seizures, respiratory arrest'

    • Gyri are inflammed

    • Hemorrhagic lesions found in coup (point of impact) and countercoup (opposite site)

  • Gross and Histopathological changes: wedge-shaped lesions (like global cerebral ischemia), edema

  • Red neurons, macrophage/neutrophil infiltration, gliosis

    

• Hematomas:

  • Epidural: skull fracture causes tearing of dural vessels (on top of dura), hematoma pushes dura matter away from skull causing subfalcine or transtentorial herniation

    

  • Subdural: Rapid movement of brain causes tearing of veins that go from brain to dural sinuses; bleeding in between dura and arachnoid matter occurs

    • Mostly asymptomatic or headache and confusion but can be life-threatening of transtentorial herniation occurs

      

Meningitis

• Define

  • Types

    • Cause

    • Clinical Manifestations

    • Lab Diagnosis

Inflammation of the arachnoid space involving the leptomeninges due to infection or chemicals/cancer

• Acute Pyogenic meningitis (bacterial):

  • Caused by:

    • Group B Strep, E. coli, Neisseria meningitides, Strep pneumoniae, listeria monocytogenes

  • Clinical Manifestations

    • Headache, neck stiffness, fever photophobia, vomiting

    • Exudate within leptomeninges, engorged vessels, suppurative exudate

  • Lab Diagnosis

    • Cloudy CSF, abundant neutrophils, elevated protein and decreased glucose

• Aseptic meningitis (viral):

  • Caused by

    • Enteroviruses

  • Clinical Manifestations

    • fever and alteration of consciousness

    • Rarely fatal, most resolve without complications

  • Lab Diagnosis: clear CSF, abundant neutrophils, protein elevated but glucose normal

Multiple Sclerosis

• Etiology

• Morphologic features

• Clinical Manifestations

• Lab Diagnosis

Inherited disease that progressively affects genes involved in myelin production

• Etiology: autoimmune response to myelin

  • More common in females and places closer to the hemispheres

  • Pathogenesis

    • Th1, Th17, CD8+ and B cells attack myelin

    • Lowered sunlight and vit D may affect

    • Susceptibility increases 3x with HLA-DRB1*1501

• Morphologic Features

  • White matter becomes has gray-tan glassy-appearing lesions

  • Macrophages loaded with myelin sheath debris (lipids)

  • MRI shows multiple areas of the CNS affected at different times

    

  • Oligoclonal Ig bands in CSF

    

• Clinical Manifestations

  • Progressive neurological deterioration that begins in infancy or childhood and results in decline of motor skills, hypotonia

  • blurred or loss of vision, vertigo, or scanning speech

Alzheimer’s disease

• Etiology

• Morphological features

• Clinical Presentation

• Etiology:

  • Risk increases with age

  • Females more affected

  • Early onset forms are due to PSEN1 mutation

  • Pathogenesis

    • Extracellularly: In amyloidogenic neurons, A-beta monomers accumulate and form neuritic plaques

    • Intracellularly: Tau protein accumulates and forms neurofibrillar tangles (flame-shaped)

      

• Morphological features:

  • Diffuse cortical atrophy makes gyri narrow and sulcus wider

  • Hydrocephalus “ex vacuo”

  • Atrophy of hippocampus causes memory loss

    

• Clinical Presentation:

  • Memory loss, difficulty performing every day tasks, disorientation

  • In final phases the patient often becomes incontinent, mute and bedridden

  • Diagnosis of exclusion

Parkinson Disease disease

• Etiology

• Morphological features

• Clinical Presentation

• Etiology: degenerative loss of dopaminergic neurons from the substantia nigra

  

• Morphological features: cytoplasmic inclusions formed by alpha-synuclein (Lewy bodies)

  

• Clinical Presentation: movement disorder

  • tremors, rigidity, bradykiesia, instability, shuffling gait

  • Progressive and sporadic

    

Types and classification of Gliomas

Gliomas

• Infiltrating Astrocytoma: headaches, seizures and focal neurological deficits; ABOVE TENTORIUM

  • Diffuse astrocytoma: low proliferation, blurring of gray-white matter interface; GRADE II MALIGNANT

    

  • Anaplastic Astrocytoma: hypercellular and increase in mitotic activity, progresses to glioblastoma in few years, GRADE III MALIGNANT

    

  • Glioblastoma: serpentine pattern necrosis, hypercellular cuffs of tumor around necrosis (pseudopalisading necrosis); GRADE IV MALIGNANT

    

• Non-infiltrating Astrocytoma: seen in children and younger adults; BELOW TENTORIUM! in the cerebellum

  • Pilocytic Astrocytoma

    • Solid tumor with cyst in the center

    • Rosenthal fibers protein aggregates and hair-like processes of bipolar cells

      

• Oligodendroglioma: GRADE I

  • Fried egg appearance due to perinuclear halo

  • Most tumors are calcified

  • Due to deletion of 1p and 19q chromosomal fragments

    

• Ependymoma: tumor in the 4th ventricle; ABOVE TENTORIUM!

  • Tumor cells form round structures around central area (rosettes)

  • Hallmark are perivascular rosettes

    

Primitive Neuroectodermal Cell Tumor

• Medulloblastoma: GRADE IV MALIGNANT

  • Homer-Wright rosettes (small round blue)

  • Spreads through CSF to spinal cord (drop metastases)

    

Arachnoid Cell Tumors

• Meningioma: GRADE I

  • Tumor of adults but more females

  • Dural-based tumor and does not involve brain, brain invasion uncommon

  • Tumor cells have Psammoma bodies form spirals