Inflammatory Disorders of the CNS

Question 1

How do young people present with MS?

Answer 1

Relapsing-Remitting (RRMS)

Question 2

How do older patients present with MS?

Answer 2

Primary Progressive (PPMS)

Question 3

What is Secondary Progressive MS?

Answer 3

RRMS that converts to PPMS

Question 4

What is clinically isolated syndrome?

Answer 4

“first attack”, ?What amount of risk of 2nd attack?

Question 5

What is Radiologically Isolated Syndrome (RIS)?

Answer 5

individuals scanned for “non”-MS symptoms, yet have apparent MS on MRI scans, ?What amount of risk of any clinical attack?

Question 6

Who is most affected by MS?

Answer 6

Women age 15-45. Incidence greater further from the equator. Most common inflammatory CNS disorder

Question 7

What is the pathology of MS?

Answer 7

Lesions Evolve Over Time
Early Perivascular lymphocytic infiltrate, with T/B cells, MΦ, complement, IgG, and complement; demyelination with relative axonal sparing
Later more of a glial scar, modest inflammation
Lymph node-like structures with B cells seen in meninges, especially in progressive MS

Question 8

What is seen on MRI in MS?

Answer 8

Gray matter lesions,seen early pathologically

Question 9

How many MS immunopathological subtypes are there in white matter?

Answer 9

four. All type IV are PPMS
Types I/II c/w encephalomyelitis
Types III/IV c/w oligodendrocyte dystrophy

Question 10

What damage is done to the neurons by MS?

Answer 10

Axonal transection

Question 11

What genes are associated with increased risk of MS?

Answer 11

Risk linked to HLA DR2; Link to IL-7 receptor, IL-2 receptor mutations; now >100 genes linked, most at odds ratios of about 1.1

Question 12

What environmental components are linked to MS?

Answer 12

EBV, cigarettes, Vitamin D deficiency, Obesity

Question 13

How is diagnosis of MS made?

Answer 13

New way:
Primarily diagnosed clinically, but MRI/CSF help define dissemination in time/space
Allow Dx after a single attack and single scan IF certain MRI features seen

Old way:
Multiple CNS Lesions
Disseminated in SPACE in CNS
Disseminated in TIME
RRMS – 2 or more clinical attacks 30+ days apart
PPMS - Minumum 12 months of progression of Sx, with disseminated lesions in space
Objective abnormalities on neurological exam
NO OTHER CAUSE IDENTIFIED

Question 14

What are the early symptoms of MS?

Answer 14

Onset most often is unifocal at first, eg, one eye, single cord lesion clinically
Numbness/tingling, Loss of Vision (optic neuritis), Gait/balance Problems, Weakness, Diplopia (double vision), Lhermitte’s (tingling down spine when flex neck), Vertigo

Question 15

What are the later symptoms of MS?

Answer 15

multifocal, and more general Sx
early symptoms, plus Fatigue, Sexual and Cognitive Dysfunction, Urinary Urgency and Frequency, Constipation, Depression, Spasticity, Dysphagia, Secondary Problems (eg, skin breakdown, infections, problems of immobility)

Question 16

What are some findings that you might have on a physical exam for a patient with MS?

Answer 16

CORTICOSPINAL – weakness, spasticity, inc reflexes
SENSORY – loss/”added” sensation; cord level
VISUAL – acuity loss, eye movement abnormalities
CEREBELLAR – ataxia, tremor, dysarthria (“Charcot’s triad”), balance, coordination
MOOD – depression, emotional lability
COGNITIVE IMPAIRMENT - ST memory, word-finding, visual-spatial function, hand-eye coordination
SEXUAL – impaired sensation or libido; erectile dysfunction

Question 17

What are some findings that you might have on an MRI for a patient with MS?

Answer 17

T1
Holes, suggest axonal damage
Enhancing lesions = Blood Brain Barrier damage
T2
Hyperintense/bright lesions
First echo (proton density), second echo (“true T2”) and Fluid Attenuated Inversion Recovery (FLAIR) or Double Inversion Recovery (DIR); Short Tau Inversion Recovery (STIR) in spinal cord
Atrophy
Focal – white and/or gray matter
Global - Brain Parenchymal Fraction
Diffusion Weighted Imaging: for acute lesions

Question 18

What are some non-specific brain MRI changes that are not MS?

Answer 18

Migraine, Hypertension, Aging

ie microvascular ischemic disease (only MS will cause spinal lesions)

Question 19

How does the CSF look in MS?

Answer 19

Protein usually less than 110 mg/dl
WBC rarely more than 40/mm3, mostly lymphs
Glucose always normal
Immunoglobulins in CSF, abnormal in about 95%
Elevated IgG Index, a quantitative index, and/or
Oligoclonal bands, a qualitative measure noted when proteins run on a gel; seen in CSF, not blood
Four or more abnormal, but now typically see 10-25
IgG gene rearrangements may predict disease activity
Myelin Basic Protein elevation non-specific
Other markers sought, ? Lipid-specific IgM bands

Question 20

What scale is used to measure disability in MS?

Answer 20

EDSS

Question 21

What is the prognosis for patients with MS?

Answer 21

Mobility – Natural history
AT 15 Y, 50% use assistive device
AT 20 Y, 50% use wheelchair
Lifespan decreased about 6-7 years
2.5 fold increase mortality vs age-matched controls
Increased risk of ICU, and mortality thereafter
Mortality especially prominent in younger patients
Suicide up to 7x more common than controls
Significant disability cause in young people
50+% enter SPMS phase, 50% by age 40-45

Question 22

What is prognosis for MS patients without therapy?

Answer 22

10-20% have “benign MS”  
Rare attacks, little disability
Post-hoc determination
About 5% have “malignant MS”
Rapidly progressive
Wheelchair-bound in 5 Years, bed-bound in 10 Years
The rest are in between

Question 23

What are the treatments for MS?

Answer 23

Behavioral change: Exercise, don’t smoke, vitamin D, sleep,?low salt-No proven diet, though there are many claims
Aggressively Treat Co-Morbidities: HTN, DM, Obesity, Spine Disease, Sleep Disturbances
Treat acute attacks to shorten them
Treat symptoms left over after attacks
Disease modifying therapies (DMT): Alter natural history of the disease

Question 24

How do you treat acute MS attacks?

Answer 24

Methylprednisone IVMP or plasma exchange

Question 25

How do you treat MS long term?

Answer 25

disease modifying drugs

Question 26

How does Natalizumab work?

Answer 26

IgG to alpha 4 integrins on leukocytes, so they can’t bind to endothelial cells at the blood brain barriers

Question 27

What is the most risky side effect with Natalizumab?

Answer 27

Progressive Multifocal Leukoencephalopathy (PML)

Question 28

What are some oral treatments for MS?

Answer 28

Fingolimod, Dimethyl Fumarate (BG12) , Teriflunomide, Lacquinimod, Estriol