BMB 2 - Multiple Sclerosis

Question 1

What is multiple sclerosis?

Answer 1

A demyelinating autoimmune disorder characterized by dissemination in space and time

Question 2

What does the term ‘transverse myelitis’ indicate?

Answer 2

Myelin damage (myelitis) that extends horizontally (transversely) across the spinal cord

Question 3

What are the four clinical subtypes of multiple sclerosis?

Answer 3

Relapsing-remitting

Primary progressive

Secondary progressive

Progressive-relapsing

Question 4

Describe the progression of relapsing-remitting multiple sclerosis.

Answer 4

Question 5

Describe the progression of primary progressive multiple sclerosis.

Answer 5

Question 6

Describe the progression of secondary progressive multiple sclerosis.

Answer 6

Question 7

Describe the progression of progressive-relapsing multiple sclerosis.

Answer 7

Question 8

Name some of the major S/Sy of multiple sclerosis.

Answer 8

Fatigue, walking issues, numbness, spasms, pain, depression, SIIN (scanning speech, intention tremor, internuclear ophthalmoplegia, incontinence, nystagmus)

Question 9

In what ways is normal neuronal action affected in multiple sclerosis?

Answer 9

Oligodendrocyte and axonal damage;

upregulation of NOGO

(NOTE: NOGO is an ‘off-switch’ for myelin production.)

Question 10

In addition to ≥1 symptom being present, a diagnosis of multiple sclerosis requires what else?

Answer 10

Dissemination over space and time

Question 11

What does it mean if a patient’s mutiple sclerosis lesions seen on MRI are gadolinium+ (i.e. take up gadolinium)?

Answer 11

The lesion occurred within the past 6 weeks.

Question 12

A patient with scanning speech and pain and numbness in certain parts of her body presents with an MRI that shows T2 hyperintensities that are >3mm, ovoid, & perpendicular to the lateral ventricles. What does this indicate?

Answer 12

‘Dawson’s fingers’ (a sign of multiple sclerosis)

Question 13

True/False.

The lesions seen in multiple sclerosis can present in various portions of the CNS and can also be either gadolinium+ or gadolinium-.

Answer 13

True.

Question 14

What would an inflammatory panel likely show in a patient with multiple sclerosis?

Answer 14

Multiple oligoclonal bands + elevated IgG index

Question 15

Which form of demyelinating disease typically presents in children as either a post-infection or post-vaccine disorder (typically ~2 weeks later) that shows all gadolinium+ lesions?

Answer 15

Acute disseminated encephalomyelitis

Question 16

Which form of demyelinating disease typically presents as the classic radiologic findings of multiple sclerosis but with no clinical symptoms?

Answer 16

Radiologically isolated syndrome

Question 17

What is the most common first symptom of multiple sclerosis?

Answer 17

Optic neuritis

Question 18

A patient’s first clinical sign of multiple sclerosis (e.g. optic neuritis prior to a diagnosis of MS) is known as what?

Answer 18

Clinically isolated syndrome

Question 19

True/False.

Multiple sclerosis is evidence of an ongoing condition with dissemination over space and time.

Answer 19

True.

Question 20

What is the likely etiology of multiple sclerosis development?

Answer 20

Genetic factors + environmental insults (e.g. EBV, low vitamin D, etc.)

Question 21

How long do the non-progressive stages of multiple sclerosis (e.g. the intial stage of relapsing-remitting before the person stops fully recovering; or the beginning of the secondary progressive form before the progressive phase is reached) typically last?

Answer 21

~10 years

(I.e. relapsing-remitting MS patients often make complete recoveries between attacks for the first 5-10 years; then they stop making full recoveries. The non-progressive stage of secondary progressive MS typically also lasts ~10 years.)

Question 22

What is a multiple sclerosis ‘relapse?’

Answer 22

An event characterized by focal neurologic symptoms (e.g. double-vision) that escalates over ~3-5 days→plateau→recovery

Question 23

How is primary progressive multiple sclerosis treated?

Answer 23

Ocrelizumab (anti-CD20)

Question 24

How is secondary progressive multiple sclerosis treated?

Answer 24

Siponimod (S1P1)

Cladribine (inhibits DNA synthesis)

Question 25

How is progressive-relapsing multiple sclerosis treated?

Answer 25

Disease-modifying therapies (e.g. interferon, natalizumab, S1P1 agents, etc.)

Question 26

The progressive forms of multiple sclerosis are characterized by a slow, insidous increase in symptom severity, usually affecting \_\_\_\_\_\_ing and ____________ first.

Answer 26

The progressive forms of multiple sclerosis are characterized by a slow, insidous increase in symptom severity, usually affecting **_walk**_ing and _**balance_** first.

Question 27

**True/False**. Specific immunotherapies for multiple sclerosis (e.g. DMTs) are preventive, but don’t necessarily cause improvement.

Answer 27

**True**.

Question 28

Optimal Vitamin ______ levels in pediatric cases of multiple sclerosis are as protective as **glatiramer** **acetate** (40% lesion reduction).

Answer 28

Optimal Vitamin **_D_** levels in pediatric cases of multiple sclerosis are as protective as **glatiramer** **acetate** (40% lesion reduction).

Question 29

There are several options for treating patients with multiple sclerosis to avoid injury (e.g. \_\_\_\_\_\_\_\_\_\_\_\_), improve conduction (e.g. \_\_\_\_\_\_\_\_\_\_\_\_), and improve energy supply (e.g. \_\_\_\_\_\_\_\_\_\_\_\_).

Answer 29

There are several options for treating patients with multiple sclerosis to avoid injury (e.g. **_disease-modifying therapies**_ improve conduction (e.g. _**dalfamprodine**_) and improve energy supply (e.g. _**biotin_**​)

Question 30

Name some of the methods of multiple sclerosis management.

Answer 30

Disease-modifying therapy Vitamin D supplementation Nutrition and exercise Sleep counseling and therapeutic community Stress management

Question 31

Via what mechanisms do interferons treat multiple sclerosis?

Answer 31

Pro- to anti-inflammatory shift (T_H1 to T_H2)

Question 32

Fingolimod and siponimod treat multiple sclerosis by interacting with which receptor? How are these medications administered?

Answer 32

S1P1 per oral

Question 33

How does natalizumab treat multiple sclerosis?

Answer 33

Anti-alpha4-integrin --- preventing T cell migration across the blood-brain barrier

Question 34

How do ocrelizumab and alemtuzumab treat multiple sclerosis?

Answer 34

**B cell depletion** (anti-CD20 and anti-CD52, respectively)

Question 35

What is a contraindication to natalizumab use in patients with multiple sclerosis?

Answer 35

**JC virus infection** (may result in progressive multifocal leukencephalopathy)

Question 36

What are the two major dangers of mitoxantrone usage in treating multiple sclerosis?

Answer 36

**Cardiomyopathy** (10%!) and therapy-related **acute** **leukemia**

Question 37

A patient presents with blurry vision, color-vision decrease, and pain behind her eyes. Assuming this is a clinically isolated syndrome (aka the first sign of multiple sclerosis), what is the likely initial diagnosis?

Answer 37

Optic neuritis

Question 38

What are some of the S/Sy associated with optic neuritis?

Answer 38

Blurry vision, color-vision decrease, pain behind the eye

Question 39

A multiple sclerosis patient presents with blurred vision, weakness, and numbness. Where do you suspect their major lesions are?

Answer 39

The brainstem

Question 40

A multiple sclerosis patient presents with spasticity, bladder incontinence, weakness, and numbness. Where do you suspect their major lesions are?

Answer 40

The spinal cord

Question 41

A multiple sclerosis patient presents with tremor, vertigo, and repeated falling. Where do you suspect their major lesions are?

Answer 41

The cerebellum

Question 42

Patients with multiple sclerosis sometimes feel an ‘electric’ sensation go up or down their spine when their neck is flexed (sometimes requires a striking of the cervical region while the head is bent forward). What is the name of this sign?

Answer 42

Lhermitte’s sign

Question 43

Name two categories of disorders that have a broad array of overlap with multiple sclerosis; i.e., presenting with optic neuritis, myelitis, and MRI findings.

Answer 43

Neuromyelitis optica spectrum disorder Myelin oligodendrocyte glycoprotein -associated disorder

Question 44

A patient with multiple sclerosis -like symptoms presents with anti-AQP4 antibodies in serum. What disorder does this indicate?

Answer 44

Neuromyelitis optica spectrum disorder

Question 45

Area postrema syndrome is mostly seen in which multiple sclerosis -like disorder?

Answer 45

Neuromyelitis optica spectrum disorder

Question 46

Why does neuromyelitis optica spectrum disorder sometimes result in area postrema syndrome?

Answer 46

There is a high concentration of aquaporin-4 in the circumventricular organs ## Footnote *(NMOSD is characterized by anti-AQ4 antibodies)*

Question 47

A patient with multiple sclerosis -like symptoms presents with anti-MOG antibodies in serum. What disorder does this indicate?

Answer 47

Myelin oligodendrocyte glycoprotein -associated disorder

Question 48

What disorder is similar to multiple sclerosis and presents with motor, sensory, bladder, and bowl symptoms and involves \> 3 spinal segments?

Answer 48

Longitudinally exstensive transverse myelitis (MS exhibits transverse myelitis but not longitudinally as in NMOSD or MOGAD)

Question 49

Is bilateral optic neuritis more common in neuromyelitis optica spectrum disorder or myelin oligodendrocyte glycoprotein -associated disorder?

Answer 49

Myelin oligodendrocyte glycoprotein -associated disorder

Question 50

Multiple sclerosis is an oligodendrocytopathy while neuromyelitis optica spectrum disorder is an \_\_\_\_\_\_\_\_\_\_\_\_\_\_pathy.

Answer 50

Multiple sclerosis is an oligodendrocytopathy while neuromyelitis optica spectrum disorder is an **_astrocyto_**pathy.

Question 51

1. Which of the following is associated with internuclear ophthalmoplegia? 2. Which is associated with edema? 3. Which is associated with area postrema syndrome? **_Neuromyelitis optica spectrum disorder_** **_Myelin oligodendrocyte glycoprotein -associated disorder_**

Answer 51

1. Neuromyelitis optica spectrum disorder 2. Neuromyelitis optica spectrum disorder 3. Neuromyelitis optica spectrum disorder

Question 52

Which form of myelin oligodendrocyte glycoprotein -associated disorder is seen in children?

Answer 52

Acute disseminated encephalomyelitis

Question 53

What CSF findings would indicate neuromyelitis optica spectrum disorder or myelin oligodendrocyte glycoprotein -associated disorder instead of multiple sclerosis?

Answer 53

**High WBC** concentration **High protein** concentration **Low** rate of **oligoclonal bands**