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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