DSA21 - CNS Pathology - Cellular Pathology through Cerebrovascular Disease

-Not capable of cell division when they mature

-Less plasticity as they mature

-Use other cells to support (glial cells)

Why are neurons so vulnerable to different insults/diseases?

-Neurofilaments

-Synaptophysin

What are examples of "immunohistochemical markers" for Neurons?

Marker for neurons able to make neurosecretory granules (aka "neuroendocrine marker")

Define Synaptophysin

Cells important for structure & metabolic functions of CNS; also important for repair and scar formation (aka "gliosis")

Define Astrocytes

Glial fibrillary acidic protein (GFAP)

What is the immunohistological stain for Astrocytes?

Astrocytes with large eosinophilic cytoplasms that respond to injury (do so by increasing cytoplasm size)

Define Gemistocytes

Densely interwoven intercellular processes forming structural component in brain

Define Fibrillary Astrocytes

Rosy, eosinophilic collections of GFAP in astrocytic processes (seen in Gliosis & Tumors - Pilocytic Astrocytoma)

Define Rosenthal fibers

Cells that create CNS myelin

Define Oligodendrocytes

Cells that line ventricles and choroid plexus (secretes CSF)

Define Ependymal Cells

Cytomegalovirus (CMV)

Ependymal cells are susceptible to what disease?

Phagocytic cells (macrophages) that ingest and break down waste products and pathogens in the CNS; come from Yolk Sac

Define Microglia (Histiocytes)

They participate in abscess wall formation

Why are fibroblasts important for the CNS?

Cerebral Edema

Define general Condition:

Excess fluid w/n brain parenchyma

Gross Path:

-Softened brain

-Flattened gyri

-Narrowed Sulci

-Compressed ventricles

Vasogenic Edema

Define Condition:

Disrupted BBB --> fluid from vessels enters extracellular space

-May be localized (due to inflammatory lesion or neoplasm)

-May be generalized

Cytotoxic Edema

Define Condition:

Increased Intracellular fluid due to cellular injury (glial or neurons)

Possible Causes = Hypoxia, Ischemia, toxin

Into subarachnoid space, then resorbed at arachnoid granules

After CSF is produced by the the choroid plexus in the ventricles, where does it go?

Increased CSF Volume in ventricles

Define Hydrocephalus

Non-communicating Hydrocephalus

Define Hydrocephalus Type:

-Obstructed CSF Flow

at Foramen of Munro or Cerebral Aqueduct

-Due to mass (tumor, hemorrhage, infection - Ependymitis from "Toxoplasmosis" or "CMV")

*Would see blocked cerebral aqueduct + temp lobe horns of lat ventricles enlarged*

-Toxoplasmosis (GENERALIZED calcifications)

-Other (Parvo B19)

-Rubella

-CMV (PERVENTRICULAR calcifications)

-Herpes/HIV/HSV

-Syphilis

Name the TORCHS infections that can cause Perinatal Brain Injury

Communicating Hydrocephalus

Define Hydrocephalus Type:

-Decreased resorption of CSF at arachnoid granulations

*May see enlarged lateral, 3rd, 4th ventricles, with 4th pushing against cerebellum*

Hydrocephalus ex vacuo

Define Hydrocephalus Type:

Large spaces develop inside cortex due to loss of cortical tissue - 'cortical atrophy' - compensatory for loss of brain volume; NOT really hydrocephalus

Head enlarges

What can happen to infants (w/ OPEN sutures) with hydrocephalus?

Their ICP increases

If an infant has hydrocephalus, BUT their sutures are fused, what happens?

May reduce blood flow to brain --> ischemia --> exacerbating cerebral edema

What is the danger with increased ICP?

Displacement of brain tissue past a rigid dural fold (falx or tentorium) or through a skull opening due to increased intracranial pressure, usually secondary to an expansile mass (tumor, abscess, or hemorrhage)

Define Brain Herniation

Subfalcine (cingulate gyrus) herniation

Define Brain Herniation:

Causes Anterior Cerebral Artery Compression -->

-Contralat leg weakness

-Aphasia IF dominant hemisphere affected

Transtentorial (uncinate, medial temporal lobe) herniation

Define Brain Herniation:

Leads to...

-CN3 compression (ipsilateral pupillary dilation)

-PCA compression (visual cortex ischemia)

-Contralat cerebral peduncle compression (Hemiparesis)

-Blood vessel shearing (Duret Hemorrhages in midbrain & pons)

Midline hematoma within tegmentum of rostral pons and midbrain. Associated with descending transtentorial herniation. Due to stretching or tearing of penetrating arteries.

Define Duret Hemorrhage

Tonsillar (cerebellar tonsils into foramen magnum) herniation

Define Brain Herniation:

Leads to...

-Brainstem Compression ==> Respiratory & Cardiac compromise ==> DEATH!

Midline malformations involving neural tissue, meninges, and / or bone and soft tissue

Linked to folate deficiency in first trimester (see elevated alpha-fetoprotein, AFP, in mother's serum)

Define Neural Tube Defects

Most common and least severe form of spina bifida without protrusion of the spinal cord or meninges

Define Spina bifida occulta

Protrusion thru lumbosacral spine; defect of meninges and spinal cord; bowel, bladder and leg deficits; skin may ulcerate with resultant infection

Define Myelomeningocele

Absence of forebrain and top of skull

Define Anencephaly

Diverticulum of malformed CNS tissue through skull defect, usually occipital or into nasal sinuses

Define Encephalocele

Small brain, often with small head (microcephaly).

Related to decreased neuron migration to cortex from germinal area near ventricles.

May be due to chromosome abnormality, fetal alcohol syndrome, viruses (HIV, Zika).

Define Microencephaly

Mutation of migration control and disrupted midline patterning: Extreme form is cyclopia

Loss of function mutation in Hedgehog signaling pathway or due to Trisomy 13

Define Holoprosencephaly

Lack of gyri (agyria)

Define Lissencephaly

Increased numbers of small irregular gyri

Define Polymicrogyria

Large brain, faulty programmed cell death

Define Megalencephaly

May present with seizure disorder; due to faulty migration of neurons from germinal matrix

Define Neuronal heterotopias

Intellectual disability (but may be normal)

Agenesis of the corpus callosum may cause what?

Malformations in small posterior fossa; may see cerebellar tonsils in foramen magnum

CSF flow may be obstructed, with compression of medulla

May cause HAs or CN deficits

Define Arnold-Chiari malformations

Relatively benign and presents during adulthood with occipital headache and cerebella dysfunction

Define Chiari type I

More SEVERE form that affects neonates and is often associated with lumbar myelomeningocele and hydrocephalus

Define Chiari type II

Surgery to enlarge posterior fossa or foramen magnum

When Chiari malformations are symptomatic, what can be done for Tx?

Enlarged posterior fossa, absence of cerebellar vermis, large midine cyst --> cystic dilation of 4th ventricle

Define Dandy-Walker malformation

Fluid filled cleft in C-spine cord with gliosis

Define Syrinx

Expansion of central spinal cord ependymal-lined canal --> can damage the anterior white commissure (cape like sensory loss distribution)

Define Syringomyelia

Vascular issue causing sudden onset of deficit of function; may be due to thrombotic occlusion (clot in place), embolic occlusion (clot from elsewhere), or vascular rupture

Define Stroke

Localized hypoxia, ischemia and infarction

When a stroke occurs due to a thrombotic or embolic occlusion in the brain, what issues usually follow?

Low O2 or Hemoglobin

Define Hypoxia

Low blood flow

Define Ischemia

Intracranial hemorrhage

When a stroke occurs due to a vascular rupture in the brain, what issues usually follow?

Neurons in hippocampus, cortex, and Purkinje cells

What neurons are most susceptible to infarction?

Accumulation of red neurons (neuronal injury) --> pyknosis/karyorrhexis (apoptosis) --> Neutrophils

What changes are seen 6-24 hours (ACUTE) after stroke in the brain?

Necrosis --> macrophages (microglia) --> vascular proliferation

What changes are seen 24h - 2 wk (SUBACUTE) after stroke in the brain?

Liquefaction --> removal of debris --> Gliosis

What changes are seen 24wks (REPAIR) after stroke in the brain?

When all voluntary and reflex functions are lost due to loss of blood flow

Define "Brain Death"

Physical destruction of the brain as observed in postmortem examinations (autolysis and liquefaction occur)

Define Respirator brain

Focal vascular lesions; extent depends on collateral blood supply, periphery (penumbra) may survive with collateral blood flow

Define Infarct

Infarcts involving periphery of arterial supply zones at sites of collateral blood flow, in global hypoxia or ischemia

Define Border Zone Infarcts ("watershed")

Arteriosclerosis

Even though spinal infarcts are rare, what can cause them?

Venous clot that lodges into systemic circulation (brain), bypassing lungs via R>L shunt (due to patent foramen ovale, ASD)

Define Paradoxical embolism

Forms when a long bone is fractured and fat cells from yellow bone marrow are released into the blood (can lead to many infarcts in brain - aka "white matter petechiae")

Define Fat Embolus

When infarct occurs upstream in cerebral vessel, this may cause vessel downstream to weaken --> when reperfusion occurs, this may damage those downstream vessels causing blood to leak out

Define Punctate hemorrhage (c/w ischemia-reperfusion injury seen from embolic infarcts)

-Deep white matter

-Basal Ganglia

-Thalamus (extending into ventricle)

-Pons

-Cerebellum

What are common sites for HTN related brain hemorrhages?

Glomerulus-like tufts arising from small arteries and arterioles (complication of longstanding HTN)

Define Arteriolosclerosis and Charcot-Bouchard aneurysms

Acute Hypertensive Encephalopathy

Define Condition:

-Diastolic BP > 130

-High ICP

-HA, confusion, vomiting, convulsions +/- coma & death

Arterioles show fibrinoid necrosis

See hemorrhage in basal ganglia here

Amyloid deposition in cerebral cortex (lobar distribution) - makes vessel walls rigid/fragile; similar to those found in Alzheimer's pts (may have Alzheimer's)

*see with Congo red stain

Define Cerebral amyloid angiopathy

Subarachnoid hemorrhage

Define Condition:

Due to rupture of saccular (berry) aneurysms in the Circle of Willis

-May be due to congenital defect in vessel wall (aneurysm lined by intima without muscular media or elastic layer)

-A/W Connective Tissue Diseases = autosomal dominant polycystic kidney disease, Ehler-Danlos Syndrome, Marfan syndrome

May bleed into subarachnoid space and/or parenchyma, cavernous malformation also - BUT less likely with capillary telangiectasia and venous angioma

How can Arteriovenous malformation (AVM) cause parenchymal hemorrhages?

Small lesions, but they may involve strategic locations (such as internal capsule)

Define Lacunar infarct/Slit Hemorrhages

dementia

After multiple infarcts occur, with a stepwise downhill course, vascular () may ensue

Head injury + Clinical syndrome that is reversible; +/- LOC and/or amnesia

Define Concussion

direct parenchymal injury where tips of gyri impact skull bone

Define Contusion

direct parenchymal injury at site of impact

Define Coup

direct parenchymal injury OPPOSITE impact site

Define Contrecoup

Old contusion with hemosiderin

Define Plaque jaune

Type of brain injury characterized by shearing, stretching, or tearing of nerve fibers with subsequent axonal damage - may be due to angular acceleration of cranium during injury, causing that stretching (Ex: Injury from Bomb Blast!)

Define Diffuse Axonal Injury

Dementia after repeated head trauma, frontal and temporal accumulation of tau neurofibrillary tangles

Define Chronic traumatic encephalopathy

Epidural Hematoma

Define Traumatic Vascular Injury:

-Parietal Fx

-Damage btwn dura and skull

-Damage to middle meningeal artery

-Pt experiences "lucid interval"

It takes time for blood to accumulate, creating pressure that causes dura to tear away from bone

Why is there a "lucid interval" when someone experiences an Epidural Hematoma?

Subdural Hematoma

Define Traumatic Vascular Injury:

-Shearing injury

-Damage btwn dura and arachnoid

-Damage to bridging veins

-Seen more in elderly (due to brain atrophy stretching veins) and infants (thin walled veins)

-May cause seizures later (from rebleeding)

Intraparenchymal hemorrhage

Define Traumatic Vascular Injury:

Bleeding within the brain tissue

-Often occurs in premature infants, bleeding within germinal matrix - near lateral ventricles

-Risk of extension into ventricular system

Localized injury to spinal cord or its roots leads to functional losses - often due to vertebral bone displacement

Define Spinal Cord Trauma

Cerebral Palsy

Define Perinatal Brain Injury:

Non-progressive motor deficit; Attributed to injury in prenatal and perinatal period

-Sx = Spasticity, dystonia, ataxia/athetosis, paresis

Periventricular leukomalacia (PVL)

Define Perinatal Brain Injury:

Ischemic infarcts in brain of premature baby/Yellow plaques of white matter necrosis and calcification of axons

Multicystic Encephalopathy

What does PVL become when the condition progresses to being "widespread"?