Multiple Sclerosis & Huntington's Disease

Question 1

HD is characterized by:

Answer 1

CHOREA AND DEMENTIA

Question 2

Principal pathologic feature of HD is:

Answer 2

severe degeneration of the basal ganglia and frontal cerebral cortex resulting in enlarged lateral ventricles

Question 3

VESICULAR MONOAMINE TRANSPORTERS:

Answer 3

tetrabenazine and deutetrabenazine

Question 4

Tetrabenazine acts by inhibiting ___________ leading to _____________ of catecholamines.

Answer 4

Acts by inhibiting VMAT2 leading to presynaptic depletion of catecholamines

Question 5

TorF: tetrabenazine is an irreversible inhibitor of VMAT?

Answer 5

FALSE. Reversible

Question 6

progressive neurological deterioration following a long period of relapsing remitting disease

Answer 6

Secondary progressive disease

Question 7

Pathological features of MS include:

Answer 7

inflammatory demyelination

axonal injury and

development of CNS lesions

which leads to diffuse, irreversible neurodegeneration

Question 8

Areas of demyelination with reactive gliosis are found in the white matter of the brain and spinal cord and in the optic nerve

Answer 8

True

Question 9

Pathogenesis of MS:

Answer 9

perpetuation of inflammatory mediators—>APOPTOSIS—>myelin sheath AXON DAMAGE

Question 10

Drugs for Relapse Prevention of MS:

Answer 10

Cladribine

Dimethyl fumarate, monomethyl fumarate

SPHINGOSINE 1‐PHOSPHATE MODULATORS

β‐1 Interferons

CD20‐DIRECTED MONOCLONAL ANTIBODY

Natalizumab
 Alemtuzumab
 Teriflunomide
 Mitoxantrone

Question 11

Drugs for High Disease Activity (Typically with Multiple Gadolinium‐Enhancing Lesions on MRI)
 Alemtuzumab
 Fingolimod
 Natalizumab
 Ocrelizumab

Answer 11

MS DRUGS

Question 12

Deoxyadenosine analog prodrug (2‐chlorodeoxyadenosine)

that preferentially depletes lymphocytes

Answer 12

CLADRIBINE

Question 13

Cladribine

Answer 13

-DEPLETES B and T lymphocytes

-Used to treat relapsing forms of MS including relapsing‐remitting
disease and secondary progressive disease

Question 14

Drugs in this class includes fingolimod, siponimod,
ponesimod and ozanimod

Answer 14

SPHINGOSINE 1‐PHOSPHATE RECEPTOR MODULATORS

Question 15

S1PRs are G protein coupled receptors that

regulate essential processes such as

Answer 15

adaptive immune cell trafficking, vascular development and

homeostasis

Question 16

S1PR modulators act by inhibiting

Answer 16

The way out of lymphocytes from lymph nodes and their

recirculation

Question 17

TorF: Finolimod Alters lymphocyte migration leading to reduction in their concentration in the CNS

Answer 17

True

Question 18

TorF: fingolimod is used to treat relapsing forms of MS including
relapsing‐remitting disease and secondary progressive disease

Answer 18

True

Question 19

GLATIRAMER

Answer 19

Is a synthetic random‐sequence polypeptide consisting
of four amino acids that resembles myelin protein (may
act as a decoy to T cell attack)

Question 20

This drug causes a deviation from the pro‐inflammatory to the anti‐inflammatory pathway

Answer 20

Glatiramer

Question 21

TorF: Glatiramer is active orally

Answer 21

False. active SQ

Question 22

Glatiramer

Answer 22

Used to treat relapsing forms of MS including relapsing‐

remitting disease and secondary progressive disease

Question 23

Drugs in this class includes interferon β‐1a, interferon
β‐1b and peginterferon β‐1a

Answer 23

beta1 interferons

Question 24

beta1 interferons act as:

Answer 24

Act as immunomodulators; decreases T cell activation

Question 25

TorF: beta1 interferons are active subquetaneously

Answer 25

False. IM

Question 26

CD20‐DIRECTED MONOCLONAL ANTIBODY

Answer 26

Drugs in this group includes ocrelizumab and ofatumumab

Question 27

CD20‐DIRECTED MONOCLONAL ANTIBODY

ocrelizumab and ofatumumab

Answer 27

Humanized monoclonal antibodies that targets CD20
antigen on B cells

 Active intravenously

 Side effects include upper/lower respiratory tract
infections, infusion reactions (e.g., pruritis, rash,
erythema, bronchospasm, throat irritation), skin
infections, herpes virus‐associated infections

 Used to treat relapsing forms of MS including relapsing‐
remitting disease and secondary progressive disease.
Also used for primary progressive MS

Question 28

NATALIZUMAB

Answer 28

Is a humanized anti‐α4 integrin monoclonal antibody

 It binds to integrins blocking their binding to their endothelial
receptors

 Acts as an immunomodulator

 Active intravenously

 Side effects include headache, fatigue, arthralgia, depression, pain in extremity, abdominal discomfort, diarrhea, nausea, rash,
hypersensitivity reactions (discontinue if occurs; do not restart) 

 Used to treat relapsing forms of MS including relapsing‐remittingdisease and secondary progressive disease

Question 29

ALEMTUZUMAB

Answer 29

Is a humanized monoclonal antibody that targets the destruction
of CD52 cells, particularly B and T cells

 Acts as an immunomodulator
 Active intravenously

Used to treat relapsing forms of MS including relapsing‐remitting
disease and secondary progressive disease in adults who have had
an inadequate response to greater than or equal to 2 years of
other MS drugs

Question 30

TERIFLUNOMIDE

Answer 30

Is a pyrimidine synthesis inhibitor

It selectively and reversibly inhibits dihydro‐orotate dehydrogenase (key mitochondrial enzyme in de novo pyrimidine synthesis pathway) leading to reduction in the proliferation of activated T and B lymphocytes without causing cell death

Used to treat relapsing forms of MS including relapsing‐remitting
disease and secondary progressive disease

Question 31

MITOXANTRONE

Answer 31

Is a cytotoxic antineoplastic agent that inhibits topoisomerase (plays a role in DNA organization)

 Induces macrophage‐mediated suppression of B cell and T
cell function; causes immunosuppression in MS patients

 Active intravenously

Used for reduction of neurologic disability and/or frequency of clinical relapses in secondary progressive relapsing or worsening relapsing‐remitting MS. Not indicated for the treatment of primary progressive MS

Question 32

Principal pathologic feature of ALS is

Answer 32

lower and upper motor neuron degeneration

Question 33

DYING‐FORWARD HYPOTHESIS

Answer 33

proposes that ALS is mainly a disorder of corticomotor neurons which connect with anterior horn cells mediate anterograde degeneration of anterior horn cells via glutamate excitotoxicity

Question 34

‘DYING‐BACK HYPOTHESIS

Answer 34

proposes that ALS begins within the muscle cells or at the neuromuscular junction. Specifically, there is deficiency of a motor neurotrophic hormone which is normally released by postsynaptic cells and retrogradely transported up the presynaptic axon to the
cell body where it acts

Question 35

Drugs used in the treatment of ALS include

Answer 35

Drugs used in the treatment of ALS include riluzole and edaravone

Question 36

Riluzole acts by

Answer 36

Acts by inhibiting glutamate release from motor neurons

Also blocks postsynaptic NMDA‐ and kainate receptors and inhibits voltage‐dependent sodium channels

Active orally

Side effects include oral hypoesthesia, asthenia, nausea,
decreased lung function, hypertension, abdominal pain, severe
neutropenia

Used for the treatment of ALS

Question 37

EDARAVONE

Answer 37

Acts as a free radical scavenger and peroxyl radical induced peroxidation systems

Potent antioxidant that prevents oxidative stress from
inducing motor neuron death in ALS patients

Active intravenously

Side effects include confusion, gait disturbances, headache, dermatitis, respiratory failure/disorders, hypoxia, glycosuria, tinea infection, hypersensitivity reactions

Used for the treatment of ALS