LEC-3 Neuropathology (1)

Question 1

Hypoxia/Ischemia results in degeneration of what neurons?

Answer 1

Hippocampus

Question 2

Huntington’s Disease results in degeneration of what neurons?

Answer 2

Caudate Nucleus

Question 3

Parkinson’s Disease results in degeneration of what neurons?

Answer 3

Substantia Nigra

Question 4

Amyotrophic lateral sclerosis (ALS) results in degernation of what neurons?

Answer 4

Motor Neurons

Question 5

What are the signs of Acute Neuronal Injury?

Answer 5

• Red neurons (eosinophilic neuronal necrosis)
• Dark & smudgy chromatin
• Hypoxic/ischemic injury
• Eosinophilic, shunken cytoplasm
• Cell death is by necrosis or apoptosis

Question 6

Myelin disorders are associated with what component of the nervous system?

Answer 6

Oligodendrocytes

Question 7

What component of the nervous system is most resistant to injury?

Answer 7

Astrocytes

Question 8

What are the major mechanisms of cellular injury?

Answer 8

• Free radical injury
• Excitotoxic injury
  
  • Excitatory amino acids: Glutamate and aspartate
  • Excitatory amino acid receptors: NMDA receptor
  • Depolarization

Question 9

Describe the excitotoxic injury.

Answer 9

Inappropriate activation of NMDA receptor that results in:

• Membrane depolarization
• Calcium influx
• Mitochondrial dysfunction

Question 10

What does subacute/chronic neuronal injury result in?

Answer 10

• Degeneration (take longer than acute neuronal injury)
• Cell loss is hard to see early on; reactive glial changes is best indication
• Cell death is mainly due to apoptosis

Question 11

What is the axonal reaction?

Answer 11

• Changes that occur in the neuron cell body in response to axonal injury
• Regenerate attempt

Question 12

What are the features of the axonal reaction?

Answer 12

• Central chromatolysis
• Damage to axon
• Margination of Nissil substance
• Central clearing of the cytoplasm
• Peripheral displacement of the nucleus
• Rounding of the cell body

Question 13

What is this image?

Answer 13

Red Neuron

Question 14

What is this image?

Answer 14

Axonal reaction

Question 15

What is this image?

Answer 15

Axonal spheroid

Question 16

Axons are highlighted as black lines with what stain?

Answer 16

Silver

Question 17

What inclusions are associated with Parkinsons?

Answer 17

Lewy body

Question 18

What inclusion is associated with Alzheimers?

Answer 18

Neurofibrillary tangles

Question 19

What inclusions are associated with Pick’s Disease?

Answer 19

Pick’s body

Fronto-temporal lobar degernation

Question 20

Neuronal inclusions may occur as a manifestation of aging, when there are intracytoplasmic accumulations of complex lipids (___________).

Answer 20

Lipofuscin

Question 21

Abnormal cytoplasmic deposition of complex lipids and other substances also occurs in ___________________________ in which substrates or intermediates accumulate.

Answer 21

genetically determined disorders of metabolism

Question 22

Viral infection can lead to abnormal intranuclear inclusions, as seen in __________.

Answer 22

Herpetic infection

Question 23

Viral infection can lead to abnormal cytoplasmic inclusions, as seen in _______.

Answer 23

Rabies. (Negri body)

Question 24

Viral infection can lead to abnormal nuclear AND cytoplasmic inclusions, as seen in _______

Answer 24

Cytomegalovirus (CMV) infection

Question 25

Abnormal vacuolization of the perikaryon and neuronal cell processes in the neuropil is seen in what disease?

Answer 25

Creutzfeldt-Jacob disease

Question 26

What is Trans-synaptic degeneration?

Answer 26

* Secondary degeneration of a neuron connected to a dying neuron * Anterograde or retrograde

Question 27

What is this image and what is it diagnostic of?

Answer 27

* Alzheimers Glia Type II * Hyperammonemia

Question 28

What is this image and what is it diagnostic of?

Answer 28

* Creutzfeldt astrocyte * Not diagnostic of any specific disease; just a reactive astrocyte * Commonly seen in demyelinating disease

Question 29

What is this image and what is it diagnostic of?

Answer 29

* Satellitosis (satelliting) * Diagnostic of oligodendroglial changes

Question 30

What is this image and what is it diagnostic of?

Answer 30

* Onion Bulb Schwaan Cell * Diagnostic of Charcot-Marie-Tooth Disease

Question 31

What is this image?

Answer 31

Large Group Neurogenic Atrophy

Question 32

What is the cause of Myasthenia Gravis?

Answer 32

Auto-antibodies against ACh-receptors at neuromuscular junction

Question 33

What are the symptoms of Myasthenia Gravis?

Answer 33

Progressive weakness throughout the day (feel fine in the morning, can't physically keep eyes open by nighttime)

Question 34

What are associated disorders of Myasthenia Gravis?

Answer 34

* Other autoimmune disorders * Thymoma/thymic hyperplasia

Question 35

What is the cause of Lambert-Eaton Syndrome?

Answer 35

Auto-antibodies against voltage-gated Calcium channels at axon terminal, inhibiting release of NT-filled vesicles following an action potenial

Question 36

What is this image?

Answer 36

Muscular dystrophy

Question 37

What does this image show?

Answer 37

* Mitochondrial disease * Ragged red fiber

Question 38

What is this image show?

Answer 38

Polymyositis: Endomysial inflammation and atrophy

Question 39

What is the cause, symptoms, and pathology associated with Polymyositis?

Answer 39

* Cause: CD8+ mediated attack on muscle cells * Symptoms: Diffuse pain * Pathology: Intrafascicular inflammation

Question 40

What does this image show?

Answer 40

Dermatomyositis: Extrafascicular inflammation and perifascicular atrophy

Question 41

What is the cause, symptoms, and pathology associated with Dermatomyositis?

Answer 41

* Cause: Antibody-mediated attack on muscle cells * Symptoms: Diffuse pain and rash * Pathology: Extrafascicular inflammation; perifascicular atrophy

Question 42

What does this image show?

Answer 42

Inclusion Body Myositis: Rimmed vacuole (with faint blue dots)

Question 43

What is the cause, symptoms, and pathology associated with Inclusion Body Myositis?

Answer 43

* Cause: Degenerative * Symptoms: Steroid resistance * Pathology: Inclusions; rimmed vacuoles

Question 44

What is the cause of Duchenne Muscular Dystrophy?

Answer 44

Dystrophin deficiency due to X-linked frameshift mutation of gene Onset: 5-6 years, death in adolescence or yound adulthood

Question 45

What is Becker Muscular Dystrophy?

Answer 45

A milder form of Duchenne MD due to a point mutation in the dystrophin gene

Question 46

What are congenital myopathies?

Answer 46

Fixed, structural defects in muscle Weakness at brith, nonprogresssive Names after histological appearance: * Central core * Rod body * Centronuclear

Question 47

What does this image show?

Answer 47

Central core myopathy

Question 48

What does this image show?

Answer 48

Rod body myopathy

Question 49

What does this image show?

Answer 49

Centronuclear myopathy

Question 50

What is the onset of Multiple Sclerosis (MS)?

Answer 50

\> 50 years

Question 51

What are the symptoms of of Multiple Sclerosis (MS)?

Answer 51

* Seeminly random * Episodic losses of neural function (vision problems, weakness in arm, parasthesia in leg) * Increased Ig levels in CSF

Question 52

What is the cause of Multiple Sclerosis (MS)?

Answer 52

Auto-immune attack of myelin (mainly CD4+ and macrophage mediated)

Question 53

What is associated with the acute phase of Multiple Sclerosis (MS)?

Answer 53

* Demyelination * Lots of immune cells near axons

Question 54

What is associated with the chronic phase of Multiple Sclerosis (MS)?

Answer 54

* Reactive astrocytosis * Axon loss

Question 55

What is the cause of Devic Disease (Neuromylitis Optica)?

Answer 55

Autoantibodies against Aquaporin-4 receptors

Question 56

What are the symptoms of Devic Disease (Neuromylitis Optica)?

Answer 56

Simultaneous blindness and paraplegia

Question 57

What is the onset of Acute Disseminated Encephalomyelitis (ADEM)?

Answer 57

A few weeks post-infection/vaccination

Question 58

What is the cause of Acute Disseminated Encephalomyelitis (ADEM)?

Answer 58

Possibly a cross-reaction with or autoimmunity against myelin

Question 59

What symptoms are associated with Acute Disseminated Encephalomyelitis (ADEM)?

Answer 59

Rapid onset of headache, lethargy, coma

Question 60

What is the onset of Acute Necrotizing Hemorrhagic Encephalomyelitis (ANHE; Weston-Hurst Disease)?

Answer 60

Shortly after UTI or M. pneumoniae infection

Question 61

What is associated with Infectious Demyelination?

Answer 61

* HIV * Progressive multifocal leukoencephalopathy (PML)

Question 62

What is Marchiafava-Bignami?

Answer 62

Demyelinating disorder that is associated with a lesion of the corpus callosum Also associated with alcoholism

Question 63

What is Demyelinating pseudotumor (tumefactive demyelination)?

Answer 63

Demyelinating disorder that has a single mass lesion that mimics a neoplasm; moderate correlation between this and the patient developing MS later on

Question 64

What is Central Pontine and Extrapontine Myelinolysis (CPM; osmotic demyelination syndrome)?

Answer 64

Primary demyelinating disease with a lesion that appears at the base of pons or any location where white and gray matter closely associate (so, most of hindbrain/parts of midbrain) * Associated with rapid correction of electrolye imbalance