Neurodegen

Question 1

What is demyelination?

Answer 1

Acquired loss of myelin WITH AXONAL SPARING
CNS: MS, viral (PML from JC), metabolic
PNS: Toxic, Inflammatory, Guillain-Barre

Question 2

What is dysmyelination?

Answer 2

Inherited, myelin not formed or is abnormally formed

• Axons tend to undergo degeneration
• LEUKODYSTROPHIES

Question 3

What is MS?

Answer 3

Autoimmune DEMYELINATING disease

Well defined episodes of neuro deficits, separated by time, white matter lesions that are separated by space

Question 4

Who most often gets MS?

Answer 4

Young Women

Question 5

What is the spectrum of MS disease?

Answer 5

Relentless to little progression

Question 6

What are the Genetic factors of MS?

Answer 6

CLASS II MHC-DR2, DR4, DR15, DQ6

15-20x if 1st degree relative

MZ twins have a greater magnitude

May be environmental: Pacific theatre WII outbreak

Question 7

What is the pathogenesis of MS?

Answer 7

CD4 T cells that attack oligos

Target: MOG (myelin oligo glycoprotein), MBP (myelin basic protein, and alpha beta crystallin

Question 8

What is the mechanism of injury for MS?

Answer 8

Antibodies and complement
- T cell induced B cell clonal expansion in CSF

Produces IgG1, IgG3

Question 9

What is the diagnostic hallmark of MS?

Answer 9

Oligoclonal banding of CSF

Ag-Ab complex recognized by Macrophages

Question 10

What is the mechanism of injury for MS?

Answer 10

Antibodies and complement
- T cell induced B cell clonal expansion in CSF

Produces IgG1, IgG3

Ag-Ab complex recognized by Macrophages and is recognized by Fc receptor

Fc receptor binding with complement causes damage to myelin leading to phagocytosis

Question 11

What is the diagnostic hallmark of MS?

Answer 11

Oligoclonal banding of CSF

Ag-Ab complex recognized by Macrophages and is recognized by Fc receptor

Question 12

What is the mechanism of injury for MS?

Answer 12

Antibodies and complement
- T cell induced B cell clonal expansion in CSF

Produces IgG1, IgG3

Ag-Ab complex recognized by Macrophages and is recognized by Fc receptor

Fc receptor binding with complement causes damage to myelin leading to phagocytosis

Lympocyte mediated injury

• T lymph prominent in early plaque formation
• Oligos are targets of cytolytic T cells

Macrophages
-Activated macros produce ROS and NOS, proteolytic enzymes, cytokines (TNF) that damage myelin

Question 13

What is the diagnostic hallmark of MS?

Answer 13

Oligoclonal banding of CSF

Ag-Ab complex recognized by Macrophages and is recognized by Fc receptor

Question 14

What are plaques in MS?

Answer 14

Actively demyelinating plaques (loss of myelin, retention of axons, myelin-laden macros
-Center of plaque is Perivascular T-cells

Inactive: Axons undergo demyleination
-Leave astros to repair (GLIOSIS)

Shadow: Remyleination occurring slowly
-LFB stain

Question 15

What are different types of MS?

Answer 15

Classic (Charcot)
Acute (Marburg)
Neuromyelitis Optica (spinal cord and optic nerves)
-Aquaporin 4 abnormalities
Schilder’s disease: Children, fulminant to remiting with steroid therapy
Concentric sclerosis (balo’s type): Very rare and diagnosed at autopsy

Question 16

What is the cause of MS neuromyelitis optica?

Answer 16

Aquaporin 4 mutation (associated with BBB abnormalities

Question 17

Who is affected by Schilder’s disease most often?

Answer 17

Children, young adults

Acute/subacute with symmetrical bilateral plaques

2x3cm involving central semiovale

No other lesions seen

Question 18

Who is affected by Schilder’s disease most often?

Answer 18

Children

Question 19

What is central pontine myelinolysis?

Answer 19

Toxic demyelination disorder

Too rapid overcorrection of hyponatremia

Due to swelling and damage to myelin sheath during the too rapid change

Question 20

What is the clinical picture of CPM?

Answer 20

Confusion, limb weakness, conjugate gaze palsies, dysarthria, dysphagia, hypotension

Question 21

What is the prognosis of CPM?

Answer 21

Poor most patients succumb within weeks

Question 22

What is Guillain Barre syndrome?

Answer 22

Acute inflammatory demyelinating polyradiculopathy

Due to infectious causes (viral, campy)

Ascending paralysis

Few patients progress to MS

Question 23

WHat is ADEM?

Answer 23

Acute disseminated encephalomyelitis

Few weeks after viral infections

HA, Vomiting, Rapid weakness, sensory loss, ataxia, visual impairment, stupor, LOC, seizures

20% succumb to disease

5-10% have relapses

Question 24

What is the range of complications with alcohol and fetal development?

Answer 24

Binge drinking results in the severe abnormalities

Behavioral and minor learning disabilities to severe facial (ocular) and cardiac defects

Question 25

What is the most common cause of Alch related death in adolescents young adults?

Answer 25

Alc poisoning and trauma

Question 26

What are the nutritional deficiencies in the alcoholic?

Answer 26

Thiamine (B1) B12

Question 27

What is a consequnce of thiamine def?

Answer 27

Wernickes encephalopathy - Necro encephalopathy with mamillary bodies, periaqueductal grey, pons and medulla - Ataxia, gaze palsies, alterned mental state Korsakoffs syndrome: Thalamic disease - Severe antegrade amnesia with confabulation

Question 28

What is a consequnce of thiamine def?

Answer 28

Wernickes encephalopathy - Necro encephalopathy with mamillary bodies, periaqueductal grey, pons and medulla - Ataxia, gaze palsies, alterned mental state Korsakoffs syndrome: Thalamic disease - Severe antegrade amnesia with confabulation

Question 29

What is a consequence of B12 deficiency?

Answer 29

Subacute combined degeneration of spinal cord Ascending and descending tract Slow onset of ataxia, tingling of legs paraplegia can develop

Question 30

What happens to the cerebellum due to alcohol?

Answer 30

Atrophy Toxic to internal granular layer of cortex (vermix) atrophy in particular

Question 31

What are alcoholics also at risk for?

Answer 31

Central pontine myelinolysis Hepatic encephalopathy Stroke Peripheral neuropathy Optic neuropathy Marchiafava-bignamic Disease

Question 32

What is marchiafava-bignami disease?

Answer 32

Itatlina men who drank red wine Toxic demyelination of corpus callosum

Question 33

What happens in lead toxicity?

Answer 33

ALtered heme prodution Delayed cognitive and intellectual development Retarded growth Learning diff and behavioral changes

Question 34

What happens in lead toxicity in adults?

Answer 34

Neurocog disease, peripheral neuropathy IRREVERSIBLE

Question 35

What happens in mercury poisoning?

Answer 35

Mild congnitive to psychiatric abnormalities to coma and death Minamata disease: Hypoesthesia of hands, feet, ataxia, visual field disturbance, dysarthria, severe encephalopathy Not reversible

Question 36

Radiology effects on CNS?

Answer 36

Methotrexate in particular and radiation causes encephalopathy with development of learning disabilities

Question 37

What does CO poisoning do?

Answer 37

It causes globus pallidus necrosis, survivors suffer movement and memory disorders

Question 38

WHat is ADEM?

Answer 38

Acute disseminated encephalomyelitis T-CELL MEDIATED HS REACTION Few weeks after viral infections HA, Vomiting, Rapid weakness, sensory loss, ataxia, visual impairment, stupor, LOC, seizures 20% succumb to disease 5-10% have relapses

Question 39

What are characteristic lesions of MS?

Answer 39

Flame lesions