2.3: 15. Neuropath #3: Infectious, Demyelinating & Storage Disorders

Front 1

Four routes of infection of the CNS

Back 1

1. Bloodstream- most common portal of entry
2. Direct Implantation- usually traumatic
3. Local Extension- usually from sinuses (bad teeth)
4. Peripheral Nervous System- conduit for some viruses, especially rabies and Herpes Simplex

Front 2

3 main infections of the CNS

Back 2

-Meningitis- Infection of meninges and CSF
-Encephalitis- Infections of brain parenchyma
-Meningoencephalitis- Infection of meninges and
brain parenchyma

Front 3

What are the central hallmarks of acute pyogenic meningitis?

Back 3

• Increased pressure
• Increased polymorphonuclear leukocytes
• Increased protein
• Decreased glucose
It is a bacterial meningitis that is result of hematogenous spread

Front 4

What infection is this a picture of?

Back 4

Acute Pyogenic Meningitis
note the pus in the subarachnoid space that sometimes can penetrate into the Virchow-robin spaces of the brain
the blood vessels are surrounded and this --> vasculitis

Front 5

What is depicted here?
What is indicated by the white circle?

Back 5

Acute Pyogenic Meningitis
White circle: neutrophilic infiltration
Lots and lots of leukocytes
Give rise to vasculitis and infarction
Doesn't happen if treated properly

Front 6

What disease does this depict?
What are 1. and 2.?

Back 6

Acute Pyogenic Meningitis
1. Vasculitis
2. Hemorrhage

Front 7

What are the most common causes of Acute Pyogenic Meningitis?

Back 7

- Neonate - Escherichia coli
• Infants and Children - Hamemophilus influenza
• Adolescents and Young Adults - Neisseria meningitidis
• Adults and Post-Traumatic - Pneumococcus

Front 8

What are the diagnostic hallmarks of Acute Lymphocytic Meningitis?

Back 8

- Lymphocytic pleocytosis
• Moderate protein elevation (< than bacterial)
• Glucose nearly normal
- Viral load increased
Associated with viral infections of the brain, mononuclear infiltrate in the CSF

Front 9

Pathologic hallmarks of Acute Lymphocytic Meningitis?

Back 9

• perivascular and parenchymal mononuclear cell infiltrates (lymphocytes, plasma cells and macrophages)
• glial nodules (microglia that begin to digest the dead neurons)
• neuronophagia
• inclusion bodies (viral factories within cells that have been infected)

Front 10

What disease does this depict? What causes this disease?

Back 10

- Viral Meningoencephalitis
- Caused by Eastern Equine virus
- in a boy scout - camping trip on block island - brain swollen, not a lot of exudate, vessels congested; others were exposed, but he was the only one who died. Immune systems can fight it
-vasculature is dilated

Front 11

What disease is depicted here? What is the arrow pointing to?

Back 11

Viral Meningoencephalitis

Arrow points to: Perivascular lymphocytic Infiltrate

Front 12

What does this image depict? What disease is present here?

Back 12

Depicts neuronophagia, in which glial cells eat infected/dying neurons

Viral Meningoencephalitis

Front 13

What does this depict What disease would you see this in?

Back 13

From Viral Meningoencephalitis - this is a microglial nodule, evidence of prior neuronophagia (glia digesting infected/dying neurons)

Front 14

What is depicted at the arrow? What disease is this evidence of?

Back 14

Eosinophilic Nuclear Inclusion, aggregates of viruses using host DNA to reproduce itself

Evidence of Viral Meningoencephalitis

Front 15

What is depicted here? What disease is this?

Back 15

This is a cell stained positively for Herpes Virus
Cause of viral meningoencephalitis

Front 16

Where does chronic meningitis usually occur? What does it cause?

Back 16

• Base of brain extending into the lateral sulci
• Obliterative endarteritis of arteries in subarachnoid space--> hyperplasia that leads to arterial occlusion and infarction

Front 17

What disease is depicted here? What is the arrow pointing to?

Back 17

- Chronic meningitis
- Black arrow = basilar exudate
- Unlike acute meningitis, where you have sugar coating in convexities, you have this at the base of the brain - far less dramatic in most instances
The disease will produce obliterative endarteritis in subarachnoid space

Front 18

What disease is depicted here? What is indicated by arrows 1. and 2.?

Back 18

- this is found in chronic meningitis
1) Obliterative Endarteritis with Intimal Hyperplasia
2) Giant Cell, produced from granulomous inflammation
This is an inflammatory infiltrate that is granulomatous; lymphocytes + plasma cells + foreign body giant cells
These can secrete things that make endothelial cells proliferate and block BV --> infarction

Front 19

What disease is depicted here?

Back 19

Fungal meningitis - a very severe case
Cryptococcal meningitis

Common cause of chronic meningitis

Front 20

What disease is depicted at the arrows?

Back 20

Cryptococcus - cryptoccocal meningitis (fungus)

Common cause of chronic meningitis

Front 21

What disease is depicted here?

Back 21

This is Candida Albicans - chronic meningitis found in immunocompromised individuals

Front 22

What disease is this? What is indicated in the circles?

Back 22

Candida Albicans (chronic meningitis)
Black circles = pseudohyphae

Front 23

What disease is this?

Back 23

Aspergillus (chronic meningitis)
Found in immunocompromised people
SEe vascocentric necrosis and hemorrhage

Front 24

What disease is this? What is depicted at 1. and 2.?

Back 24

Aspergillus (chronic meningitis)
1. True Hyphae
2. Necrotic Blood Vessels
This disease usually only infects those that are immunocompromised

Front 25

What causes brain abscesses? What are the pathological hallmarks of brain abscesses?

Back 25

• direct implantation, local extension or hematogenous spread
• associated with acute bacterial endocarditis, cyanotic congenial heart disease and chronic plumonary sepsis
• anaerobic streptococci, Bacteroides fragilis, aerobic streptococci and staphylococci most common pathogens

• focus of necrotizing cerebritis
• fibrous capsule produced by fibroblasts derived from blood vessels
• zone of gliosis outside fibrous capsule
A local infection where the body walls it off, creates fibrous capsule to wall it off

Front 26

What disease process is depicted here?

Back 26

Brain Abscess

Front 27

What disease process is present here? What cells are present?

Back 27

Brain abscess

Absess filled with polymorphonuclear leukocytes, macrophages
Pool formation of reticulin, congeals into fibrous capsule

Front 28

What is depicted here? What disease process is this indicative of?

Back 28

Reticulin in blood vessels; this proliferates to wall off pus from a BRAIN ABSCESS from the rest of the brain

Front 29

What is indicated by the arrow on the left? What about the arrow in the right?

Back 29

L: Pus (this is a brain abscess)
R: Fibrous Capsule left behind after pus removal
This could be a location of seizure focus

Front 30

What are 4 syndromes caused directly by HIV?

Back 30

1. acute meningitis or encephalitis
2. subacute encephalitis
3. vacuolar myelopathy
4. peripheral neuropathy
(but we rarely see these because of the treatment of HIV now)
No inclusion bodies

Front 31

What disease is this indicative of? What is circled in black?

Back 31

These are multinucleated giant cells of monocytic origin which are hallmarks of HIV meningitis

Front 32

What disease is this indicative of? What is circled in black?

Back 32

These microglial "stab" cells are found in HIV and syphilis-related meningitis
Stab cells are slender knife-like microglial cells

Front 33

What is depicted here?

Back 33

Viral particles within an infected neuron

Front 34

What is depicted at the arrow?

Back 34

Toxoplasmosis - found in patients who are immunocompromised; this is a secondary infection in the brain
Has mulberry appearance in toxo cyst

Front 35

What is depicted at the arrow?

Back 35

This is Toxoplasmosis
At the arrow, you see "Mulberry" appearance of a toxo cyst

Front 36

What is depicted at the arrow?

Back 36

A toxo cyst; as seen in Toxoplasmosis

Front 37

List 5 prion diseases.

Back 37

• Creutzfeldt-Jakob Disease (sporadic and hereditary)
•Kuru
•New Variant CJD (Mad Cow Disease)
•Fatal Familial Insomnia (hereditary)
•Gerstmann - Straussler Disease (hereditary)

Front 38

Creutzfeld-Jakob disease: symptoms, pathology, and etiology

Back 38

• Rapidly progressive dementia with myoclonus and periodic EEG pattern
• Spongiform  encephalopathy  with  “kuru”   plaques in 5-10%
• Etiology thought to be accumulation of abnormal  “prion”  protein, cause other proteins to misfold
Both sporadic and hereditary

Front 39

What disease is this?

Back 39

Cruetzfeldt-Jakob Disease
• Rapidly progressive dementia with myoclonus and periodic EEG pattern
• Spongiform  encephalopathy  with  “kuru”   plaques in 5-10%
• Etiology thought to be accumulation of abnormal  “prion”  protein, cause other proteins to misfold
Both sporadic and hereditary

Front 40

What disease is depicted here? What are the white bubbles indicative of?

Back 40

CRUETZFELDT- JAKOB DISEASE

Prion protein accumulates, forming white bubbles

Front 41

What disease is depicted here? What is at the arrow?

Back 41

CRUETZFELDT- JAKOB DISEASE

Arrow: Prion protein accumulates, forming white bubbles

Front 42

What is depicted here?

Back 42

Spongiform Transformation in molecular layer of the cerebellum
Can occur because of prion diseases

Front 43

What disease is depicted here?

Back 43

Multiple Sclerosis: Demyelinating Disease
You can see the sharply demarkated area of demyelination (red arrow)
Demyelination usually perivenous- formation of plaques

Front 44

What is depicted here?

Back 44

MS plaques
Demyelination usually perivenous
Seen often in the cerebrum, optic, brainstem, and spinal cord

Front 45

What disease is this? What is depicted at the arrow?

Back 45

Multiple Sclerosis
Arrow: Area of demyelination
Sharp line where demyelination occurs

Front 46

What disease is this? Which side is myelinated and which side is demyelinated? Which is normal

Back 46

MS
L: abnormal, demyelinated
R: normal myelin

Front 47

What is notable about this slide? What disease is it?

Back 47

MS - notable because axons are preserved, but myelin is missing

Front 48

What are the morphological features of MS?

Back 48

Topography
1. Cerebrum, optic, brainstem, spinal cord
2. Predominately white matter with grey matter affected 3. Asymmetric, discontinuous and unsystemized
4. Periventricular and subcortical
5. Sharp demarcation of grossly intact tissue
Histopathology
1. Perivascular (venous)
2. Oligodendrocytes diminished
3. Perivascular and meningeal mononuclear infiltrate 4. Myelin loss
5. Axons spared
6. Macrophage formation with sudanophilic breakdown 7. Concentric spread

Front 49

What disease is this?

Back 49

Variant of MS: Devic's disease
Demyelination limited to optic chiasm and spinal cord
Defect in aquporin 4

Front 50

What disease is this? What is indicated at the arrows?

Back 50

MS in the optic chiasm
The arrows show demyelination

Front 51

What disease is this? What is indicated at the arrow?

Back 51

MS Variant: Balo's Concentric Sclerosis
Arrow: Concentric lesion in cerebral white matter
Tiger striped lesion is distinct

Front 52

What is depicted here? What is indicated at the arrows?

Back 52

Post-Infectious Encephalomyelitis or ADEM: Acute Disseminated Encephalomyelitis

Arrow: multi-focal perivenular demyelination

This is LIKE MS, but gets better; found in the context of a previous infection
ADEM is an autoimmune disease usually triggered by viral infection, but can also occur due to vaccine
Note: caused because health Nazis make us get flu shots.

Front 53

What disease is depicted here? What is at the arrow?

Back 53

ADEM: Acute Disseminated Encephalomyelitis

Arrows: Perivascular Demyelination

Front 54

What is depicted here?

Back 54

Acute hemorrhagic leukoencephalitis
Can occur from demyelination (like from ADEM) when it becomes hemorrhagic (fatal)

Front 55

Antecedent events for Guillain-Barre Syndrome

Back 55

1.VIRAL INFECTIONS Measles
Mumps
Rubella
Influenza A
Influenza B Varicella-zoster Cytomegalo virus Epstein-Barr virus Infectious mononucleosis Vaccinia
Variola
Infectious hepatitis Coxsackie
ECHO

2. Other infections
Mycoplasma pneumoniae Salmonella typhi Camphylobacter jejuni Listerosis
Brucellosis Tularemia Ornithosis

3. VACCINES
Rabies Swine Flu
4. Surgery
5. Fever therapy
6. MALIGNANCY
Hodgkin’s  disease
Carcinoma Lymphoma
7. PREGNANCY
USUALLY PRESENTS AFTER GASTROINTESTINAL ILLNESS

Front 56

What is depicted here? What causes this?

Back 56

Central Pontine Myelinolysis
Death of oligodendrocytes and corresponding loss of myelin in the pons
cause: rapid correction of hyponatremia
Can --> quadriplegia

Front 57

What is depicted here?

Back 57

Central pontine myelinolysis
Death of oligodendrocytes and corresponding loss of myelin in the pons
cause: rapid correction of hyponatremia
Can --> quadriplegia
Axons are preserved and inflammation is absent

Front 58

What is this a picture of?

Back 58

Progressive Multifocal Leukoencephalopathy (PML)
Caused by papovaviridae- usually in immunocompromised patients

Front 59

What is depicted here?

Back 59

Oligodendroglial nuclear inclusions
Characteristic of progressive mulitfocal leukoencephalopathy

Front 60

What is depicted here?

Back 60

"Bizarre astrocytes"
Characteristic of progressive mulitfocal leukoencephalopathy

Front 61

What is depicted here?

Back 61

JC virus on EM
We all have this virus, all kept in check
Usually limited to immunocompromised patients

Front 62

What is depicted here?

Back 62

Adrenoleukodystrophy
Arrows point to areas of dysmyelination
Failure of normal myelin to form
This leads to macrophages to digest the abnormal myelin

Front 63

What is depicted here? What is at the arrow?

Back 63

Adrenoleukodystrophy
Failure of normal myelin to form
Macrophages digest the abnormal myelin

Front 64

What is depicted here?

Back 64

Metrachromatic Leukodystrophy

Front 65

What is depicted here? What is at the arrow?

Back 65

Alexander's Disease
Arrow: Rosenthal fibers

Front 66

What disease is depicted here?

Back 66

Tay Sach's disease
A storage disease in which there is a deficiency in hexosaminadase A
Leads to the death of neurons, kills children from a young age

Front 67

What disease is this? What is at the arrow?

Back 67

- Tay Sach's
- Swelling in the neuronal cytoplasm
From the buildup of lysosomal products that cannot be broken down since there is a deficiency of hexosaminadase A
Leads to death of neurons and early childhood death