The “Nuts and Bolts” of Multiple Sclerosis

Rebecca Milholland, M.D., Ph.D.

Center for Neurosciences

Objectives • Discuss which patients are at risk for Multiple

Sclerosis

• Discuss the diagnostic criteria for the diagnosis of

Multiple Sclerosis

• Discuss the types of and progression of Multiple

Sclerosis

• Discuss treatment options for Multiple Sclerosis.

Multiple Sclerosis - Epidemiology • Smoking – increased over all risk and prognosis

• Vitamin D Deficiency

• Genetic o 0.1% general population

o Monozygotic twins 30% correlation

o Dizygotic twins 4%

o Sons 1%

o Daughters 4%

o Sex, 3 Women: 1 Man

• Age – 20-50

Diagnosis • Cardinal Features of Multiple Sclerosis Attack

• Neurological Examination with Deficits

• MRI brain and total spine, with and without contrast

• CSF: oligoclonal bands and IgG index elevation

• Somatosensory, Visual Evoked Potentials

• Watch for Multiple Sclerosis Mimics

MacDonald Criteria; separation in

time and space

• Revised 2010, and updated 2011

• By MRI

o Simultaneous presence of asymptomatic enhancing and

non-enhancing lesions

o OR new T2 lesion or gad-enhancing lesion on follow up MRI

• By clinical Exam AND MRI

o Typical lesions on MRI

o History of at least one exacerbation with typical deficits

Multiple Sclerosis Mimics

• Migraine

• Vascular Disease

• Vasculitis

• Radiologically Isolated Syndrome/Clinically Isolated

Syndrome

• ADEM (Acute Disseminated Encephalomyelitis)

Vasculitis

Date: 22 Nov 2011Pages: 15, Chapter Category:Neurodegenerative Disease Taken from the Book: Neurodegenerative Diseases, Book Series: Special Books Edited by: Shamim I. Ahmad

Acute Disseminated

Encephalomyelitis

oAcute CNS demyelinating disease

o Follows infection

oAccompanied by a mental status change and fever

o Predominance in children

oOccurs over days to weeks

Radiographic Isolated Syndrome

• Lesion typical for Multiple Sclerosis found as an

incidental finding on MRI without clinical symptoms.

• 30-35% convert to clinically isolated syndrome within

2-3 years.

• 90% demonstrate a diagnosis of Multiple Sclerosis by

current criteria.

Clinically Isolated Syndrome

• Clinical syndrome typical for multiple sclerosis with a

corresponding T2 lesion MRI.

• 30-70% convert to multiple sclerosis within 5 years.

• Most often lesions in the optic nerve, brain stem,

and spine.

Forms of Multiple Sclerosis • Relapsing Remitting:

o Repeated clinical attacks with stability between.

• Secondary Progressive MS: o Progressive impairment between or in the absence of attacks

o Disease modifiers no clear effect.

• NO history of attacks with resolution o Progressive myelopathy with accompanying dysfunction.

• NMO – neuromyelitis optica: o Large initial lesion in the cervical spine

o More aggressive form of Multiple Sclerosis

o anti-aquiporin 4 antibodies

Determination of Therapeutic Goals

• Reduce the frequency of relapses.

• Reduce the numbers of lesions forming over time.

• Reduce disability accumulation.

• Avoid long-term disability.

Fingolimod (FTY720) • Mechanism of Action

o Prevents T cell entry into CNS by trapping them in the peripheral lymph

nodes.

• Monitoring

o Baseline CBC and liver panel

o Opthalmological examination

o Cardiac Status

o Varicella Immune Status

• Initiation: 6 hr observation, for first dose bradycardia

o CBC, Hepatic Panel

o Opthalmologic Exam 3-4 months

o Monitor BP

PML Risk With Natalizumab • Progressive multifocal leukoencephalopathy

o Subacute progressive demyelinating disease caused by JC virus.

o Symptoms:

• Progressive hemiparesis

• Speech disturbance

• Visual field cut

• Cognitive dysfunction – confusion and personality changes

o Prognosis – poor, usually death

o MRI findings, extensive, confluent lobar areas of T2 signal change

BG12 • Nrf 2 activation, possibly activating apoptosis.

• Oral agent

• Side Effects o Flushing

o Diarrhea

o Nausea

o Abdominal pain

o Leukopenia, not associated with adverse effects

• Monitoring – CBC and CMP after 3 months

Knowledge Assessment 1. What percentage of clinically isolated syndrome patients convert to MS?

a) 5% b) 10% c) 20%

d) > 30%

2. The standard treatment for a pregnant MS patient is no treatment. a) True b) False

3. Existing MS therapies include a) Intravenous b) Infusions c) Oral Medications

d) All of the above