Demyelinating Disorders

Question 1

An autoimmune disease characterized by Chronic Inflammation, Demyelination, Gliosis(plaque or scarring) and Neuronal loss?

Answer 1

Multiple Scerosis

Question 2

Diagnosis of Multiple Sclerosis

Answer 2

Clinical History
MRI
CSF analysis (Oligoclonal Bands)

Question 3

Target cells of Multiple Sclerosis

Answer 3

Oligodendrocytes

Question 4

What is the first manifestation of Multiple Sclerosis?

Answer 4

Impaired Vision

Question 5

Genetic Predisposition of MS is associated with?

Answer 5

HLA-DRB1

Question 6

Periventricular demyelinated sclerotic plaque (Dawson’s fingers) (FLARE MRI)

Answer 6

MRI of Multiple Sclerosis

Question 7

Periventricular Inflammation Infiltrate

Answer 7

Histology of MS

Question 8

IgG oligoclonal bands in the CSF on gel electrophoresis

Answer 8

Lab findings of MS

Question 9

Cause: Reactivation of Latent JC virus
Risk Factors: long term treatment with monoclonal antibodies (Natalizumab) in MS, HIV patients

Answer 9

Progressive multi focal Leukoencephalopathy

Question 10

Overly aggressive correction of hyponatremia

Answer 10

Osmotic demyelination syndrome

Question 11

Disease of White Matter in CNS ———-and disease of White matter in PNS —————

Answer 11

Multiple sclerosis; Guillain Barre syndrome

Question 12

Course: Chronic Relapsing (classical)
Episodic neurologic signs and symptoms: Disseminated in time and space
Peak age: 20-40yrs more common in women.
Attack followed by complete or partial remission

Answer 12

Multiple Sclerosis

Question 13

Types of Multiple Sclerosis

Answer 13

Question 14

What are the environmental factors of MS?

Answer 14

Vitamin D deficiency
Smoking
EBV- Epstein-Barr Virus

Question 15

What are the immunologic Pathogenesis of MS?

Answer 15

For specific reason unknown, some T-cell escape the BBB activating Microglial function with cytokines infiltration aka Periventricular infiltrate

Question 16

Clinical Presentation and Lab Findings of MS

Answer 16

Female pt (20-40y/o) presents with (optical neuritis) PERIORBITAL PAIN preceded with visual loss; worsens by exercise or a HOT BATH/ feel very HOT (Uhthoff Phenomenon); weakness of the limbs- upper motor Neuron type; Diplopia (double vision), May be Atexia; Vertigo; LHERMITTE’s symptom (neck flexroom may cause an electric shock-like sensation radiates down the back of legs; Bladder dysfunction (>90% of MS patients); Sensory: Paresthesia and Hypesthesia

Question 17

What triggers Perivenular cuffing in MS

Answer 17

Some T cells comes in brain parenchyma, identify myelin as a foreign antigen, this is expressed and they start secreting cytokines which damages tight junctions causing Periventricular infiltrate, predominantly T-cells and macrophages

Question 18

MRI of areas of demyelination in MS

Answer 18

Question 19

Cells targeted in MS ————— cell targeted in Gulian Barre Syndrome

Answer 19

Oligodendrocyte (CNS); Schwann Cells (PNS)

Question 20

Treatment of Acute Attack of MS?

Answer 20

Corticosteroids - High dose for Short term or intravenous Methylprednisolone

Question 21

Treatment for Remitting and Relapsing MS

Answer 21

Natalizumab
Rituximab
Mitroxantrone
Cladribine

Question 22

Drug MOA for MS: humanized monoclonal antibody against Alpha -4 ( a-4) integrity
Reduce the transmission of immune cells into the CNS by interfering with the alpha4Beta 1-integrins receptor molecules in the surfaces of cells

This drug increases the risk of progressive Multifocal Leukoencephalopathy

Answer 22

Natalizumab

Question 23

Acts against CD 20

Answer 23

Rituximab

Question 24

MOA of MS drug: Anti-tumor antibiotic acts by suppressing the activity of T-cells, B-cells, and macrophages that lead the attack on the Myelin sheath

Answer 24

Mitoxanthrone (Drug of last result for secondary MS)

Question 25

MOA of MS drug: Depletes B Cells

Answer 25

Cladribine

Question 26

MOA for MS drugs: composed of 4 amino acids and bare similar structure to myelin proteins; acts as decoy to T-cells; shifts the population of T-cells from pro inflammatory Th1 T-cell to regulatory Th2 T-cells that suppresses the inflammatory response

Answer 26

Glatiramer

Question 27

MOA of MS drugs: increases the cytotoxicity of natural killer cells and increases the phagocytosis activity of macrophages

Answer 27

Beta interferon: Interferon Beta -1a

Question 28

MOA of MS treatment: Selective sphingosine-1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction

Answer 28

Fingolimod/Siponimod

Question 29

Answer 29

Methylprednisolone

Question 30

Multifocal areas of demyelination of varying size, throughout the brain, sparing SPINAL CORD AND OPTIC NERVES, caused by Reactivation of LATENT JC VIRUS

Answer 30

Progressive Multifocal Leukoencephalopathy (PML)

Question 31

An MS patient on Natalizomuab what kind of condition can they develop?

Answer 31

PML- progressive Multifocal Leukoencephalopathy 5% of AIDS pt develops PML

Question 32

Another name for Osmosis demyelination syndrome

Answer 32

Central Pontine Myelinolysis

Question 33

Demyelination WITHOUT inflammation in the base of the Pons, with relative sparing of axons and nerve cells. Bilateral corticospinal and corticobulbar tracts are affected

Answer 33

Osmotic demyelination syndrome or Central Pontine myelinolysis (if it’s in the pons)

Question 34

Cause of Osmotic Demyelination Syndrome (ODS)

Answer 34

Overly rapid correction of hyponatremia

Question 35

Clinical features: Quadriparesis, psuedobulbar palsy (dysphagia, dysphonia, dysarthria (diff. Speaking); Lock-in-syndrome - absent motor function but maintain INTACT Sensation and Cognition

Answer 35

Osmotic Demyelination Syndrome

Question 36

Chronic alcoholic patient (develops hyponatremia) was corrected what is the pathophysiology

Answer 36

Osmotic demyelination syndrome (ODS) due to abrupt correction to chronic hyponatremia by MASSIVE ASTROCYTIC DEATH leading to Demyelination

Question 37

Pathophysiology of Osmotic Demyelination Syndrome

Answer 37

Question 38

What is the main cell targeted in Osmotic Demyelination Syndrome?

Answer 38

Astrocytes - forms the BBB