8 - Multiple Sclerosis Flashcards by Andrea Okas

What is multiple sclerosis?

Leading cause of non-traumatic brain disease in young people
Characterized by episodes of focal disorder of the central nervous system
Demyelinating and axonal disease
Affects the white matter predominately, but also affects the grey matter
An autoimmune disease (but not a classic autoimmune disease)

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What type of nerological findings will you see in MS?

** TAKE HOME **

MS only gives you upper motor neuron findings

NOT both upper and lower

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Which part of the brain does it affect the most?

White matter

But also grey matter - BOTH

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What type of a disease is MS predominately?

Demyelinating

But also, axonal disease - BOTH

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Describe MS as an autoimmune disease

(but not a classic autoimmune disease)

- More of an autoimmune-mediated disease

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Describe the epidemiology of MS

Approximately 400,000 Americans are afflicted with M.S.

- Peak age of onset is about 30(typical range 18-55)

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What factors contribute to MS?

Unknown etiology

Geographical factors
Familial factors (but not a strict Mendelian inheritance)

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What is the gender variation in MS?

Ratio of females to males is 2-3:1 in the United States

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What is the geographical variation in MS?

Geographical variation:

- Incidence of M.S. increases with increasing latitude

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Describe the etiology of MS

The cause of multiple sclerosis remains unknown
Neurotropic viruses, bacteria and numerous environmental toxins have been implicated.
EBV (Epstein Barr virus) titers are present in almost all MS patients and levels are increased during acute MS attacks.
80% have had exposure to EBV, but unknown if this is the case

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Describe the genetics that contribute to MS

Prevailing hypothesis is that M.S. is a polygenic disease
Only one genetic factor of confirmed importance- HLA class II region of chromosome 6
Predominantly a disease of caucasians
20% of patients have a family history of at least one additional case of M.S.

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What is the risk of other family members getting MS?

High concordance rate of 30% in monozygotic twins
2-6% risk with a full first degree relative
1.1-1.4% risk with a half sibling
Adoption and general population (0.1%)

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What is the gene that is the most implicated in MS?

HLA class II regions

HLA-DR-DQ haplotype HLA-DRBI*1501
DRB50101, DQA10102, DQB1*0602 increases the risk for M.S. three to four times

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Describe the immunological attack seen in MS

Predominantly an aberrant T-cell immune response(B-cells and macrophages play a lesser role)
Activation of circulating CD4 cells specific for myelin basic protein, proteolipid protein, MOG, and MAG.
Dysfunction in the BBB allowing the activated cells to cross into the CNS attacking myelin.
A normal BBB would not allow cells to cross, so there is a defect in the BBB of MS patients

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What are the four types of clinical courses of MS?

Relapsing-remitting MS
Primary progressive MS
Secondary progressive MS
Progressive relapsing MS

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What type do 85% of patients have at diagnosis?

Relapsing-remitting MS

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What type of MS do we have good treatment for?

The active, relapse form (attacks of MS)

- No good treatment for just primarily progressive MS

What is the disease severity we see with MS?

Disease Severity:

Benign 10-20%
Malignant 10%
Intermediate 70-80%

How do you know which type your patients will have?

Prognostic indicators

What are the poor prognostic indicators?

Poor prognostic indicators

male
older age at onset
posterior fossa symptoms at onset
African-American
Significant residual disability from first attack

How do you diagnose MS?

It is a diagnostic challenge

No blood test
History
Neurologic Exam
M.R.I. (FLAIR, Gad, spectroscopy)
CSF studies (IgG is highly indicative of MS)
Evoked potentials (visual evoked response test)

What is key?

** TAKE HOME **

HISTORY
- If you have taken a history and you have no clue and you think the testing is going to tell you, you need to go back and take a better history

What do you need to listen to in the clinical history diagnosis?

Age, race, gender, rearing

- Symptoms referable to the CNS

What do you need to do in the neurological exam when diagnosing MS?

Signs referable to the CNS

- Solid findings such as extensor plantor responses, RAPD, INO, optic disk edema more helpful

What do you look for on an MRI scan when looking for MS?

- Spots in the corpus collosum - Light spots in the middle of the brain - These are lesions in the brain and can indicate MS - These spots could be caused by a stroke or something else when seen throughout the brain - If you see it in the corpus collosum specifically, be highly suspicious of MS

What do you look for in teh spinal fluid when looking for MS?

- Pleocytosis of typically less than 50 wbc and only very rarely above 100 wbc - Non-specific elevation in protein - Elevated IgG synthesis rate - Presence of oligoclonal IgG bands You should NOT have antibodies and immune cells in the brain, so it indicates a breech in the BBB Remember IgG ***

What "evoked potetials" will you see in the physical exam on an MS patient?

- VER most helpful *** - BAER-possibly helpful if brainstem lesion suspected - SSEP-possibly helpful if spinal cord lesion suspected

What is Neuromyelitis Optica?

AKA Devic's disease An ONLY B-cell mediated disease

Describe the features of neuromyelitis optica

- B-cell mediated disease - Aquaporin-4 ab (NMO-IgG) - Transverse myelitis and often bilateral O.N. - Initial cranial MRI often normal - Longitutinally extensive spinal lesions (very big lesions) Often times blind and quadraplegic

What is acute disseminated encephalomyelitis?

ADEM - Febrile illness - Much more common in children - Typically involves grey and white matter of the CNS - Typically monophasic

What drug can you use in MS patients to improve gait?

AMPRYA (4-aminopyridine)

How does AMPRYA (4-aminopyridine) improve gait in MS patients?

- Showed improvement in gait based on 25 foot timed walk. - May reduce motor fatigue - Sustained release prep is well tolerated - Sz

What is very common for MS patients to take?

Supplements Always ask!

What is the ONLY supplement that is recommended?

Vitamin D Proven effects!

Describe the effects of vitamin D on MS

- Recent study showed an association of low 25-hydroxyvitamin D levels with an increased incidence of M.S. - EAE treated mice exhibited a less severe disease course when treated with Vitamin D. - Osteoporosis/ osteopenia are under-diagnosed and under-treated in MS. Treatment with Calcium/ Vit D is recommended - Recommend serum D level of ~50.

What is the other actual treatment of MS?

Immunomodulation

What are the immunomodulation options?

- Beta interferon therapy - Glatiramer acetate - Mitozantrone - Natalizumab - Fingolimod There are risks associated with each of these

Some of these have become available as a pill. What are the benefits and issues with this?

- The pills have tolerance issues that shots do not have - Other side effects like GI and diarrhea can be present - However, patients can get "needle fatigue" and get sick of always taking shots, so a pill is nice for them

Describe the drug research focus currently

We are focused on repair of the neurological system

What is the first drug that has been shown to be effective in primary progressive MS?

LISTEN *** At the very end