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Multiple Sclerosis Flashcards

1
Q

What is MS?

A

chronic disease of the CNS
-hits the brain and spinal cord

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2
Q

Which sex is impacted by MS the most?

A

women ~ 3:1
-males tend to have a more severe course

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3
Q

What is the leading cause of non-traumatic disability in young adults?

A

MS

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4
Q

Describe the pathophysiology of MS.

A

inflammation <–> demyelination <–> axonal degeneration in the CNS

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5
Q

Describe the distribution of MS.

A

highest prevalence in North America
-less sunlight = less vit D??
-3rd world countries = poor health care = under identified??

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6
Q

Describe the etiology of MS.

A

immunological
genetic
-not entirely, one twin may develop while the other may not
environmental
-nothing identified as causative
infectious
-Epstein Barr = 32x more likely to develop MS
etiology is unknown, interplay of genetics + triggers

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7
Q

What are some of the many potential symptoms of MS?

A

numbness, tingling
vision problems
dizziness
cognitive dysfunction
depression
fatigue
muscle spasms
weakness
walking difficulty
pain
bladder dysfunction
bowel dysfunction
unique:
-Lhermitte’s Sign
-Uhtohoff’s Phenomena
-MS Hug

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8
Q

What are the different types of MS?

A

relapsing-remitting
-most common type
-fine –> episode –> repeat
primary progressive
-no episodes
-continual increasing disability over time
secondary progressive
-not returning to baseline, permanent disability
-most ppl with relapsing-remitting develop this type
clinically isolated syndrome
-episode of sx and then never having another attack

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9
Q

What is key to recognize regarding inflammation and the different types of MS?

A

inflammation is high during active relapses but inflammation actually decreases with time
-many drugs work on inflammation, over time they may have nothing to work on

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10
Q

How is progression measured in MS?

A

Expanded Disability Status Scale
-focuses mainly on mobility
-doesnt capture cognition or upper limb mobility

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11
Q

What is the EDSS score that signifies the person with MS can no longer mobilize?

A

6
-we dont know how drugs work on people with a score of 6 or higher

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12
Q

What is the non-pharmacological management of MS?

A

exercise
-old thoughts were take it easy = no longer the case
diet
-just overall healthy eating
complementary/alternative medicine

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13
Q

What are the 3 approaches to pharmacological management of MS?

A

treat acute relapses
treat/manage symptoms
prevent disease activity and progression

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14
Q

What is an MS relapse?

A

new or worsening symptoms
lasts 24 hours or longer
absence of fever (infection) or other causes
separated from previous relapse by 30 days or more

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15
Q

What is the treatment for an MS relapse?

A

high-dose steroids
-methylprednisolone 500-1000 mg IV x 3-5 days
-oral prednisone 1250 mg = 1000 mg IV MP

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16
Q

What is the therapy for a MS relapse non-responsive to high dose steroids?

A

may consider plasma exchange

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17
Q

True or false: all MS relapses are treated

A

false

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18
Q

Differentiate primary and secondary fatigue.

A

primary - caused by MS
-more energy needed because of damaged CNS
secondary - caused because of living with MS
-depression, pain, spasms, sleep disturbances

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19
Q

What is the non-pharm management for fatigue?

A

OT/PT
-helping focus where to use energy
sleep hygiene
avoid excessive heat
exercise and diet

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20
Q

What are the pharmacological options for fatigue?

A

amantadine
-insomnia
modafinil
-HA, insomnia, SJS, fetal abnormalities
methylphenidate
-insomnia, anxiety, dizziness
these dont work very well, limited evidence

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21
Q

What are the non-pharm options for gait?

A

OT/PT
bracing/walking aids
exercise

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22
Q

What is the pharmacological option for gait in MS?

A

fampridine
-indicated to increase walking speed (?benefit)

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23
Q

What are the adverse effects of fampridine?

A

UTI
insomnia
headache
dizziness
seizure risk (dose-dependent)

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24
Q

Can fampridine be used in pregnancy?

A

pregnancy and breastfeeding risk unknown

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25
What are the non-pharmacological options for spasticity in MS?
exercise stretching
26
What are the pharmacological options for spasticity in MS?
baclofen 5-10 mg TID -GI issues, drowsiness gabapentin 900 mg TID -drowsiness, nausea, blurred vision botulinum toxins q3-6 mo -pain, bruising
27
Which cannabis product is used in MS?
Sativex -indicated as add-on treatment of spasticity and pain in MS -lack of evidence for use in any other MS symptoms
28
What are the potential ADRs of Sativex?
dizziness blurred vision tachycardia falls fatigue long-term cognition effects
29
What are the current challenges with cannabis in MS?
dosage/ratio unknown type of cannabinoid(s) to use varying quality/quantity if street cannabis finding cannabis "naive" study participants
30
What are the potential benefits of disease-modifying therapies?
attempt to slow the inflammatory process decrease frequency and severity of relapses decrease lesions on MRI reduce accumulation of neurological impairment and disability over time (?)
31
When is it best to start disease-modifying therapies?
earlier is better
32
Which DMTs are injectable?
interferon beta-1b glatiramer acetate interferon beta-1a peginterferon beta-1a oftatumumab
33
Which DMTs are oral?
fingolimod dimethyl fumarate teriflunomide cladribine siponimod ozanimod ponesimod
34
Which DMTs are infused?
natalizumab alemtuzumab ocrelizumab rituximab
35
What are the two main MOAs of DMTs?
immunomodulator immunosuppressant
36
Which DMTs are examples of immunomodulators?
interferon-beta glatiramer acetate
37
Which DMTs are examples of immunosuppressants?
dimethyl fumarate teriflunomide fingolimod siponimod ozanimod ponesimod natalizumab ocrelizumab ofatumumab alemtuzumab cladribine
38
What is PML?
progressive multifocal leukoencephalopathy -rare, but often fatal -opportunistic infection by JC virus -destroys the cells that produce myelin
39
What is the cure for PML?
no cure - "fix" the reason for immune suppression -stop meds (plasma exchange if needed)
40
Which DMTs is PML seen most often with?
natalizumab (highest risk) dimethyl fumarate fingolimod ocrelizumab
41
What increases the risk for PML?
JCV + prior immunosuppressant > 2 yrs use (natalizumab)
42
How frequently are the injectable DMTs given?
interferon beta 1b: SC EOD interferon beta 1a: IM weekly or SC 3/week peginterferon beta 1a: SC q2/52 glatiramer acetate: SC OD or SC 3/week ofatumumab: week 1-3 SC weekly then SC q 4 wks
43
What are the monitoring parameters for interferon DMTs?
CBC and LFT every 6 months or prn *same monitoring parameters for ofatumumab*
44
What are the common adverse reactions for interferon DMTs?
injection site reactions flu-like symptoms hepatotoxicity lymphopenia
45
What are the adverse reactions of glatiramer acetate?
injection site reactions post injection systemic reactions lipoatrophy*
46
What are the monitoring parameters for glatiramer acetate?
no monitoring required but watch for lipoatrophy
47
What are the adverse reactions of ofatumumab?
injection site reactions URTI headache potential for serious infections (HBV reactivation) PML occurred with higher doses when used for chronic lymphocytic leukemia
48
How frequently are the oral DMTs dosed?
teriflunomide: OD dimethyl fumarate: BID fingolimod: OD siponimod: OD ozanimod: OD cladribine: OD for 4 or 5 days beginning each of first 2 months of years 1 and 2 of treatment
49
Which oral DMTs are potential teratogens?
teriflunomide (M & F) fingolimod (2-3 month washout) siponimod (washout 10 days) ozanimod (2-3 month washout) cladribine (M & F)
50
What are the adverse reactions of teriflunomide?
diarrhea/nausea hair thinning hepatotoxicity peripheral neuropathy headache
51
What are the adverse reactions of dimethyl fumarate?
flushing GI intolerance (nausea/diarrhea) lymphopenia* PML (rare)
52
What are the adverse reactions of fingolimod?
bradycardia/atrioventricular conduction slowing (prolonged QT) macular edema herpes simplex infections HTN hepatotoxicity PML (rare)
53
What are the adverse reactions of siponimod?
HTN bradycardia headache, dizziness lymphopenia diarrhea/nausea pain in hands and feet (and/or swelling)
54
What are the adverse reactions of ozanimod?
infections (URTI, nasopharyngitis, UTI) bradycardia (temporary) HTN lymphopenia
55
What are the adverse reactions of cladribine?
nausea headache thinning hair flu-like symptoms increased infections (vaginal, shingles, oral herpes)
56
What are the monitoring parameters for teriflunomide?
baseline pregnancy test baseline TB test CBC LFT monthly x 6/12 then q 6/12
57
What needs to be reinforced with teriflunomide?
contraception -up to 2 years post-drug or rapid elimination protocol
58
What are the monitoring parameters for dimethyl fumarate?
CBC
59
What are the monitoring parameters for fingolimod?
baseline LFT baseline VZV status (vaccination if negative) baseline ECG; further cardiac assessment if necessary baseline ophthalmological assessment then at 3-4mo then prn baseline pregnancy test *first dose cardiac observation for 6 hours*
60
What are the monitoring parameters for siponimod?
similar to fingolimod but no cardiac observation with first dose unless cardiac history CBC and LFT
61
What are the indications for siponimod?
SPMS and RRMS -only drug that has an indication for SPMS
62
What are the monitoring parameters for ozanimod?
similiar to siponimod CBC and LFT
63
What are the monitoring parameters for cladribine?
baseline pregnancy test baseline VZV status baseline CBC monitor for TB infection monitor for Hep B and C CBCs
64
What needs to be reinforced with cladribine?
contraception -for 6 months after last dose
65
How frequently are the infused DMTs dosed?
natalizumab: IV q 4/52 ocrelizumab: IV at week 0 and 2 then IV q 24 weeks alemtuzumab: first course IV for 5 consecutive days then second course IV for 3 consecutive days at month 12 from initial course rituximab: IV week 0 and 2 then q 6/12
66
What are the adverse reactions of natalizumab?
hypersensitivity reactions hepatotoxicity headache infections (UTI, LRTI) joint pain *PML (especially if used > 2 yrs)
67
What are the adverse reactions of ocrelizumab?
infusion reactions (premedicate with IVMP and antihistamine 30-60 min prior to infusion) increased risk of infections (LRTI, URTI, viral, conjunctivitis) reactivation of HepB depression and feelings of self harm *PML potential*
68
What are the adverse reactions of alemtuzumab?
infusion reactions (up to 2 h after infusion finished) autoimmune thyroid disorders immune thrombocytopenic purpura glomerular nephropathies increased risk of infections (UTI, URTI, viral) increased risk of malignancy
69
Which infused DMTs are potential teratogens?
ocrelizumab
70
What are monitoring parameters for natalizumab?
baseline JCV status baseline brain MRI baseline CBC baseline LFT JCV status q 6-12 months MRI brain q 6-12 months LFT q 6 months CBC PML monitoring
71
What are monitoring parameters for ocrelizumab?
*hepatitis B screen (avoid ocrelizumab)*
72
What are the indications for ocrelizumab?
PPMS and RRMS -only one indicated for PPMS
73
How long should pregnancy be avoided after the last infusion of ocrelizumab?
avoid pregnancy for 6-12 months after last infusion
74
How long do the adverse reactions of alemtuzumab need to be monitored?
up to 4 years after last dose -especially autoimmune ADRs
75
What are monitoring parameters for alemtuzumab?
baseline: CBC, SCr, LFT, TSH, VZV titer, HIV, hepatitis serology baseline pregnancy test baseline TB test baseline skin exam to monitor for melanoma baseline screening for HPV and cervical dysplasia
76
How is rituximab used in MS?
used off-label in MS -actually works really well in MS
77
What does rituximab have the potential for?
PML
78
What are factors to consider when choosing a DMT?
patient factors: -age -sex -lifestyle factors -pregnancy/breastfeeding disease factors: -disease course -prognosis -disease activity induction vs escalation
79
What are some important notes regarding pre-pregnancy and MS?
no effect of MS on fertility dont routinely defer DMT consider effect of exposure in males pregnancy does not affect long-term disability outcomes relapse risk during and after pregnancy
80
What are some post-partum considerations in MS?
support breastfeeding alongside treatment considerations methylprednisolone not CI in breastfeeding increased of post-natal depression
81
Does MS make a pregnancy automatically high-risk?
not automatically
82
What are the 1st line injectable DMTs in pregnancy?
Copaxone/IFN-B preparations -safe to continue until conception -no evidence of harm to fetus -if stopped, 3/12 to reach full efficacy post-partum -benefits of breastfeeding on treatment outweigh risk
83
Which DMTs are contraindicated in pregnancy?
teriflunomide ocrelizumab fingolimod cladribine
84
Describe vaccine use in MS patients.
inactivated vaccines = generally safe live and live-attenuated = generally not recommended -esp if taking DMT wait until 4-6 weeks after relapse onset
85
What is generally a good idea to do with MS patients and vaccines?
consider referring -complex patients on complex drugs

PHAR358 (20 decks)

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