Multiple Sclerosis (overview)

define multiple sclerosis

• most prevalent chronic autoimmune, inflammatory disease of CNS

• characterized by plaque-like sclerosis disseminating in time and space

what are the 2 pathological hallmarks of MS

1. inflammation with demyelination

2. astroglia proliferation (gliosis) and neurodegeneration 

RRMS: Women ____ Men

>

PPMS: Women ___ men

<

what are some causes of MS

• 1st degree relative

• monozygotic twins

• identifiable gene variants

• obesity

• smoking

• Temperature/climate

• vitamin D deficiency

• waning latitude 

• Epstein Barr virus

This was developed in response to the importance of MRI guided diagnosis

McDonald Criteria 

Prioir to the initial criteria development in 2001, how were patients classified

early, probable, or possible

Define clinically isolated syndromes (CIS)

refers to a 1st episode of neurologic symptoms that lasts at least 24 hours and is cause by inflammation of demyelination but does not yet meet the diagnostic criteria for MS

true or false: MS is curable

false

what should providers be focused on with tx for MS

• Treating acute attacks

• ameliorating symptoms of disease

  • Reducing biologic activity with disease-modifying therapy (DMT)

around how many different DMT classes exist without formal, evidence based algorithms to guide provider and patient decisions 

9

DMTs are prescribed to do what

reduce relapses and new MRI lesion activity

DMTs are not prescribed for 

symptoms improvement for people with MS

2018 AAN practice recommendations for DMT initiation include

• counseling patients on DMTs

• prescribe highly effective treatments for patients with highly active disease

• evaluate barriers to adherence

• Evaluate the risk vs benefits of DMTs to people with a single clinical demyelinating event and 2 or more brain lesions

• consider serial imaging at least annually for the first 5 years and close follow-up rather than initiating DMT in people with CIS

• consider reproductive therapy and needs for men and women

what classifies mild disease

interpretation of radiographic and/or clinical burden along with concern for future disease to be lower

what classifies moderate disease

greater concern about future disease course or accumulation of disease activity 

what classifies markedly active disease

neurologic or radiographic worsening or demonstration of significant burden of disease in recent past

clinical measures for prognostic markers to evaluate for tx initation

• male sex

• >50 y.o at onset

• severity and frequency of relapses

• rapid accrual of disease

• relapse type (motor vs brainstem vs sensory)

MRI measures for prognostic markers to evaluate for tx initiation 

• T2 lesion burden 

• gadolinium-enhancing lesions (GEL)

• Presence of persistent T11 hypointense lesions

• spinal cord or infratentorial lesions 

what makes up the escalation approach or “treat to target” approach

• use of moderate-efficacy, relatively safe DMT followed by surveillance

• if there is an inadequate response or tx failure, the patient is switched to a more effective agent

• match disease activity and tx effects

what makes up the early, highly effective tx approach

• evolving area of research that is subject to interpretation

• Initiation of high-efficacy therapies in tx of naive patients after diagnosis

• may prevent progression in the crucial, early tx window and prevent future disability

what did phase 2 trials of new outcome measures focus on

MRI outcomes 

what did phase 3 new outcome measures focus on

overt clinical outcomes, including annual relapse rate (ARR)

MS is usually diagnosed between ages ___ to ____

20-50 y.o

there are over _____ different DMTs

20

what are some autoimmune processes involved with the proposed patho of MS

• breakdown of BBB

• multifocal inflammation

• demyelination

• oligodendrocyte loss

• reactive gliosis

• axonal degeneration

what are some primary symptoms of MS

• visual complaints

• gait problems/falls

• paresthesia

• pain

• weakness

what classifies primary symptoms 

• direct consequences of conduction disturbances produced by demyelination and axonal damage 

• correlate to the area of CNS that is damaged 

what characterizes secondary symptoms

complication resulting from primary symptoms

what characterizes tertiary symptoms

effects of disease on every day life

examples of secondary symptoms

• recurrent UTIs

• urinary caliculi

• osteomyelitis 

• poor nutrition 

• depression

• respiratory infections

examples of tertiary symptoms

• financial problems

• social dysfunction

• emotional imbalance

define acute exacerbations

new neurologic symptoms lasting at least 24 hours or more in the absence of fever or active infection

what are some possible relapse triggers

• recent infection

• sleep deprivation

• malnutrition

• anemia

• organ dysfunction

• exertion

• childbirth

define unilateral optic nerve

gradual, painful vision loss and/or altered color vision

define lhermitte’s phenomenon

electric shock-like sensation when flexing the neck

define “MS hug”

tight, band like sensation around the trunk or abdomen 

define myelitis

weakness in arms/legs

sensory symptoms

bladder or bowl dysfunction

what are two important tests that help characterize time and space in diagnosing MS

MRI and CSF

how to treat exacerbation

methylprednisone 1000 mg IV daily for 3-5 days

Prednisone 1250mg orally for 3-5 days

drug of choice of treating an exacerbation

methylprednisolone

what to do in patients who do not improve with high dose steroids can be evaluated for _____ or _____

PLEX or IVIG 

escalation approach involves what type of DMTs

immunomodulatory

early high-effective treatment involves what type of DMTs

immunosuppressive

what are some barriers to adherence

dosing frequency

dosing route

ADR

depression

$$

what’s the main difference between immunomodulatory vs immunosuppressive DMTs

immunomodulatory alters immune signals without cytotoxic effects or bone marrow suppression, whereas immunosuppressive DMTs alters with

key DMT recommendations

• initiate FDA-approved DMT therapy ASAP

• therapy should be continued indefinitely unless there is lack of benefit, poor adherence or intolerable side effects

• choice of DMT should be made collaboratively 

• limited head-to-head data between DMT therapy 

• considerations for switching therapies 

true or false: absence of relapses does justify discontinuation of DMT therapy

false

true or false: DMTs can be considered for patients with CIS likely to progress to MS

true

meds to help with spasticity

baclofen 

tizanidine

dalfampridine

cannabidiol

meds for bladder symptoms

oxybutynin

TCAs

solifenacin

darifenacin

mirabegron

tolterodine

meds for sensory symptoms

gabapentin

pregabalin

duloxetine

meds for fatigue 

amantadine

antidepressants

modafinil 

true or false: there is no standard definition of tx failure

true