September 24, 2009; Khonkaen

Multiple Sclerosis For Non Neurologists

Naraporn Prayoonwiwat, M.D.

Neurology Division, Department of Medicine

Siriraj Hospital
sinpy@mahidol.ac.th
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02 419 7101-2

Multiple Sclerosis
MS is a rare disease, it is unlikely to be seen in my general practice.

Do you think so?

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Case Presentation
Eye: A young woman had dimmed vision of the left eye for 2 days. Eye drop tried without improvement. Vision got worse. Pain on eye movement was noted. Diagnosis: optic neuritis Rx: high dose steroids
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Case Presentation
ENT: A young woman felt spinning for a few days, getting worse with motion. There was no hearing loss or visual blurring. Diagnosis: vertigo Rx: antivertigo drug
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Case Presentation
Urology: A young woman difficulty in voiding for 3 days. Urinalysis: WBC 3-5, RBC 5-10, few bacteria Diagnosis: acute urinary retention Rx: Foleys catherization, quinolone
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Case Presentation
GI: A middle age woman had nausea and vomiting for 5 days. She had very frequent hiccoughs for 1 day. EGD: showed mild gastritis Diagnosis: acute gastritis Rx: intravenous PPI
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Case Presentation
Orthopedics: A middle age woman had gait difficulty 2-3 weeks. She could not properly lift her feet above the ground. There was some numbness at the lower legs. Diagnosis: lumbar spondylosis Inx: CT myelogram
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Case Presentation
Skin: A middle age man experienced itching at the anterior chest left side for 1 week. No rash was noted.

Diagnosis: dermatitis Rx: topical steriods

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Case Presentation
Surgery: A middle age woman had headache for 1-2 months. She could not do her routine work, was slow in response. Mild weakness was noted. Inx: CT brain with contrast -mass Diagnosis: brain tumor
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Multiple Sclerosis
The neurological deficits in these patients were caused by demyelinating disease of the CNS. All of had MS.

Do you agree?

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Demyelinating Disease
What is a demyelinating disease of the CNS? What is the significance of myelin?

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Demyelinating Disease
Myelin wraps around the nerve axon and contributes to the conduction velocity of the nerve.

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Demyelinating Disease
Oligodendrocytes are responsible for myelin production in the CNS; while Schwann cells are responsible in the PNS.

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Demyelinating Disease
Diseases affecting the CNS myelin cause white matter lesions in the CNS, whereas diseases affecting the PNS cause demyelinating type of peripheral neuropathy.

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Myelinated neuron

Immunopathogenesis
Information flow Autoimmune attack
Demyelinated neuron

Partial Information flow

Degenerated neuron

No Information flow Disabilities Neurological symptoms

Nerve Conductions
Myelinated fiber Node of Ranvier

axon

Demyelinated fiber

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Demyelinating Disease
What is MS?

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Multiple Sclerosis
An immune-mediated disorder involving mainly the white matter (myelin) of the CNS which affects susceptible individuals of both sexes after exposure to certain environmental factors.

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Multiple Sclerosis
- Immune-mediated disorder of the CNS - White matter (myelin) involvement - Response to environmental factors in susceptible persons - Affect both sexes

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Multiple Sclerosis
Scope: Clinical manifestations Pathology Pathogenesis Diagnosis Treatment in MS
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Multiple Sclerosis

Clinical Presentation
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Clinical Presentation
Cerebrum Optic nerve Cerebellum/cerebellar pathway Brainstem Spinal cord Bladder & Bowel function Other
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Multiple Sclerosis

Clinical Presentation
Cerebrum Cognitive impairment : deficits in attention, reasoning, executive function (early) dementia (late) Hemiparesis: UMN Hemisensory loss
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Multiple Sclerosis

Clinical Presentation
Cerebrum (2) Affects (mainly depression) Epilespy (rare) Focal cortical deficits (rare) Psychiatric symptoms (rare)

Multiple Sclerosis

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Clinical Presentation
Optic nerve Unilateral painful loss of vision : scotoma : reduced visual acuity : impaired color vision : relative afferent pupillary defect (RAPD)
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Multiple Sclerosis

Clinical Presentation
Cerebellum/cerebellar pathway Tremor : postural tremor : intention tremor Clumsiness and poor balance : limb in-coordination : gait ataxia
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Multiple Sclerosis

Clinical Presentation
Brainstem Diplopia (double vision) Internuclear ophthalmoplegia: INO Nystagmus Vertigo

Multiple Sclerosis

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Clinical Presentation
Brainstem (2) Dysarthria (slurred speech) Dysphagia (swallowing difficulty) Pseudobulbar palsy

Multiple Sclerosis

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Clinical Presentation
Spinal cord Weakness : upper motor neuron signs Stiffness : spasticity Painful spasms
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Multiple Sclerosis

Clinical Presentation
Spinal cord (2) Bladder dysfunction Erectile dysfunction (impotence) Constipation

Multiple Sclerosis

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Clinical Presentation
Other Pain Fatigue Paroxysmal symptoms Temperature sensitivity Exercise intolerance
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Multiple Sclerosis

Common Presentations
Optic neuritis acute visual loss, intraorbital pain on eye movement Acute myelitis limb weakness, numbness, urinary retention Brainstem diplopia, INO, facial numbness, hemiparesis, hemisensory loss, ataxia
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Multiple Sclerosis

Functional Status System

Cerebrum Optic nerve Cerebellum/cerebellar pathway Brainstem Spinal cord Bladder & Bowel function Other
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Multiple Sclerosis

Clinical Course

Relapsing-remitting: RR

Progressive-relapsing: PR

Secondaryprogressive: SP
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Primary-progressive: PP

Clinical Course
Clinical threshold Axonal loss Brain volume

Inflammation RR PR

Relapses PR SP PP

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RR

Expanded Disability Status Scale

Multiple Sclerosis
Scope: Clinical manifestations Pathology Pathogenesis Diagnosis Treatment in MS
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Multiple Sclerosis

Pathology
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MS: Pathology
Active Lesion

MRI
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Gross

Luxol fast blue

Frohman EM, et al NEJM 2006;354:942-55

MS: Pathology
MS Plaque: Acute
LFB stain Numerous macrophage Loss of myelin

Perivascular infiltrates

MRP14 (Macrophage)

PLP mRNA in situ hybridization

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Toluidine blue

Electron Micrograph

Frohman EM, et al NEJM 2006;354:942-55

Demyelination

MS: Pathology
MS Plaque: Chronic
Demyelinated area
Astrocyte No Oligodendrocyte

Chronic gliotic lesion

Numerous macrophage

LFB stain

Toluidine blue

Microglia nuclei

Astrocyte Macrophage

Demyelinated axon

Remyelinated axon
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Frohman EM, et al NEJM 2006;354:942-55

EM

MS: Pathology
Demyelination-Remyelination
EM

Demyelinated axon

Remyelinated axon

Demyelination

Remyelination

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Frohman EM, et al NEJM 2006;354:942-55

MS: Pathology
Active Lesion Demyelina5on

Loss of OPC

OPC preserved

OPC: oligodendrocyte progenitor cell

Werkle H and Lassmann H in McAlpines MS 4th Ed. 2005

MS: Pathology
Active Lesion Remyelina5on

Early

Completed

OPC: oligodendrocyte progenitor cell

Werkle H and Lassmann H in McAlpines MS 4th Ed. 2005

MS: Pathology
Active Lesion
Demyelina5on Remyelina5on

Werkle H and Lassmann H in McAlpines MS 4th Ed. 2005

MS: Pathology
Chronic Lesion
Demyelina5on Remyelina5on

Arrest of remyelina5ng process

Werkle H and Lassmann H in McAlpines MS 4th Ed. 2005

Template SR

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sinpy@mahidol.ac.th

March 26, 2009

02 419 7101-2

Multiple Sclerosis
Scope: Clinical manifestations Pathology Pathogenesis Diagnosis Treatment in MS
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Multiple Sclerosis

Pathogenesis
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Autoreactive Tcells T Activation via APC, T

Differentiation, Proliferation

Trigger

Pathogenesis
T T T
Adhesion/ attraction BBB IFN-

Periphery

T
Transmigration

T T APC
APC

B
Antibodies

M

TNF-

Release of cytokines Recruitment of M

Nitric Oxide

Local reactivation TNF-

CNS

Demyelination and axon loss

Adapted with kind permission from Prof. R. Hohlfeld

Multiple Sclerosis
Scope: Pathology Pathogenesis Clinical manifestations Diagnosis Treatment in MS
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Multiple Sclerosis

Diagnosis
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Multiple Sclerosis Diagnosis

Schumacher Poser McDonald Revised 1965 1983 2001 2005*

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Recommended Diagnostic Criteria for MS: Guidelines from International Panel. McDonald et al. Ann Neurol 2001;50:121-7 *Diagnostic Criteria for Multiple Sclerosis: 2005 Revisions to the McDonald Criteria. Polman, et al. Ann Neurol 2005;58:840-6.

Multiple Sclerosis Diagnosis

Schumacher Poser McDonald Revised 1965 1983 2001 2005*

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Recommended Diagnostic Criteria for MS: Guidelines from International Panel. McDonald et al. Ann Neurol 2001;50:121-7 *Diagnostic Criteria for Multiple Sclerosis: 2005 Revisions to the McDonald Criteria. Polman, et al. Ann Neurol 2005;58:840-6.

Multiple Sclerosis Diagnostic Consideration

Objective evidence of dissemination in time and space Clinical evidence: presence of clinical signs history of symptoms: insufficient
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Ann Neurol 2001;50:121-7

Multiple Sclerosis Investigations

Magnetic resonance imaging Evoked potentials: visual auditory somatosensory motor CSF analysis cell count IgG index oligoclonal band
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Multiple Sclerosis
MRI Criteria MRI criteria:
Dissemination in space brain MRI spinal cord MRI Dissemination in time

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Barkhof F. Brain 1997;120:2059-69 Tintore M. Am J Neuroradiol 2000;21:702-6

Multiple Sclerosis
MRI Criteria MRI criteria:
Dissemination in space brain MRI spinal cord MRI Dissemination in time

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Barkhof F. Brain 1997;120:2059-69 Tintore M. Am J Neuroradiol 2000;21:702-6

Dissemination in Space Brain MRI criteria:

9 T2 hyperintense lesions or 1 Gd-enhancing lesion in 4 > 1 infratentorial lesion 3 > 1 juxtacortical lesion Spinal cord (subcortical U-fiber) > 3 periventricular lesions
Lesion > 3 mm in cross section
d NP Barkhof F. Brain 1997;120:2059-69 Tintore M. Am J Neuroradiol 2000;21:702-6

Multiple Sclerosis

3 in 4
1)

Dissemination in Space
or

MRI Criteria for

>9
2)

T2W lesions
3)

>1
4)

Gd+ lesion

>1 Infratentorial
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>1 Juxtacortical

> 3 periventricular

Barkhof F. Brain 1997;120:2059-69 Tintore M. Am J Neuroradiol 2000;21:702-6

3 in 4
1)

Dissemination in Space
or

MRI Criteria for

>1
2)

Gd+ lesion
3)

>9
4)

T2W lesion

>1 Infratentorial
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>1 Juxta-

cortical

Barkhof F. Brain 1997;120:2059-69 Tintore M. Am J Neuroradiol 2000;21:702-6

> 3 periventricular

Nine or more hyperintense lesions in T2 (or FLAIR)

T2W
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FLAIR
Ann Neurol 2001;50:121-7

One Gd enhancing lesion in T1

T1W
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T1W c Gd

Ann Neurol 2001;50:121-7

At least one infratentorial lesion

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Ann Neurol 2001;50:121-7

At least one juxtacortical lesion

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FLAIR

Ann Neurol 2001;50:121-7

At least three periventricular lesions

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FLAIR

Ann Neurol 2001;50:121-7

Multiple Sclerosis
MRI Criteria MRI criteria:
Dissemination in space brain MRI spinal cord MRI Dissemination in time

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Barkhof F. Brain 1997;120:2059-69 Tintore M. Am J Neuroradiol 2000;21:702-6

Dissemination in Space Spinal MRI criteria:

Little or no swelling of cord T2 hyperintense lesions - size > 3 mm - length < 2 vertebral segments - partial involvement of cord (cross section)
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Multiple Sclerosis

Ann Neurol 2001;50:121-7

3 in 4
1)

Dissemination in Space
or

MRI Criteria for

>1
2)

Gd+ lesion
3)

>9
4)

T2W lesions

Note =

>1 Infratentorial
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>1 Juxtacortical

> 3 periventricular

Barkhof F. Brain 1997;120:2059-69 Tintore M. Am J Neuroradiol 2000;21:702-6

Little or no cord swelling

T2W T1W w Gd

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Ann Neurol 2001;50:121-7

T2W lesion > 3 mm

T2W T2W

Cervical cord
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Length <2 vertebral body segments

T2W T1W w Gd

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Ann Neurol 2001;50:121-7

Partial involvement of cord

T2W T2W

Cervical cord
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Dissemination in Space Spinal MRI criteria (revised):

A spinal lesion is equivalent to a brain infratentorial lesion An enhancing spinal lesion equals to an enhancing brain lesion Individual spinal lesions count together with individual brain lesions
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Multiple Sclerosis

Ann Neurol 2005;58:840-6

Dissemination in Space (spinal)

1) 2)

MRI Criteria for

= 1
3)

= Infratentorial lesion 1 Gd + lesion

count each spinal = together with each brain lesion

Ann Neurol 2005;58:840-6

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Brainstem and spinal lesion

T2W

Ann Neurol 2005;58:840-6

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One spinal lesion can be substituted for one infratentorium brain lesion.

Spinal Gd-enhanced lesion

T2W T1W w Gd T2W

Cervical cord One spinal Gd lesion can be substituted for one Gd brain lesion.

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Multiple Sclerosis
MRI Criteria MRI criteria:
Dissemination in space brain MRI spinal cord MRI Dissemination in time

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Barkhof F. Brain 1997;120:2059-69 Tintore M. Am J Neuroradiol 2000;21:702-6

Dissemination in Time a. 1st scan >3 mo of clinical onset:

Gd positive lesions; not at the site implicated in the original clinical event Follow-up scan ~ 3 mo New T2 lesion New Gd positive lesion
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Multiple Sclerosis

2001

Ann Neurol 2001;50:121-7

Dissemination in Time b. 1st scan <3 mo of clinical onset:

No Gd positive lesion Follow-up scan > 3 mo of onset New Gd positive lesion If not Follow-up scan > 3 mo of 1st scan New T2 lesion New Gd positive lesion

Multiple Sclerosis

2001

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Ann Neurol 2001;50:121-7

Dissemination in Time
Clinical event
3 months 3 months

MRI Criteria for

2001

yes

Category 1

yes

Gd +ve New T2
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yes
Ann Neurol 2001;50:121-7

Dissemination in Time a. 1st scan >3 mo of clinical onset:

Gd positive lesions; not at the site implicated in the original clinical event

Multiple Sclerosis

b. 1st scan >1 mo of clinical onset; Follow-up any time after 1st scan Revised New T2 lesion
2005
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Polman et al. Ann Neurol 2005;58:840-6

Dissemination in Time
Clinical event
3 months

MRI Criteria for

2001

yes yes

Category 2
Gd +ve New T2
Ann Neurol 2001;50:121-7

yes

3 months

Dissemination in Time
clinical event
Category 1 yes yes yes yes
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MRI Criteria for

3 months yes

2001

3 months

yes

Category 2

Gd +ve New T2

3 months

Ann Neurol 2001;50:121-7

Dissemination in Time
clinical event
Category 1 1 month Category 2 yes 3 months yes Gd +ve New T2

MRI Criteria for

Any time
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Revised 2005

Polman et al. Ann Neurol 2005;58:840-6

Multiple Sclerosis
Investigation
Magnetic resonance imaging Evoked potentials: visual auditory somatosensory motor CSF analysis cell count IgG index oligoclonal band
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Multiple Sclerosis
Investigation

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Visual Evoked Potentials

Multiple Sclerosis Investigations

Magnetic resonance imaging Evoked potentials: visual auditory somatosensory motor CSF analysis cell count IgG index oligoclonal band
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Multiple Sclerosis
Investigation
Serum: + CSF : ++

Serum CSF

Serum: CSF : ++

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CSF oligoclonal bands

Multiple Sclerosis
Diagnostic Criteria

Primary Progressive Multiple Sclerosis Clinical Data Additional Data 1 year of disease progression (prospectiveretrospective) Plus 2/3 of
Ann Neurol 2005;58:840-6

Revised 2005

Brain MRI positive 9 T2 lesions > 4 T2 lesions + VEP Spinal MRI positive 2 focal T2 lesions CSF positive OCB or IgG index
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Criteria: Primary Progressive MS

Progressive course 1 y
Brain
or + VEP

Plus 2/3 of Spinal

CSF - Oligoclonal bands - IgG index

>4 T2W

2
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Revised 2005
Ann Neurol 2005;58:840-6

Multiple Sclerosis

Differential Diagnosis
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Differential Diagnosis
ADEM APL syndrome SLE CNS vasculitis Behcets disease 1o Sjogren syndrome CADASIL Sarcoidosis CNS infection: HIV, PML, SSPE, Lymes disease, meningovascular syphilis, Whipples disease Mitochondrial 1o CNS lymphoma encephalopathy
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ADEM: acute demyelinating encephalomyelitis, APL: antiphospholipid, SLE: systemic lupus erythematosus, CNS: central nervous system, CADASIL: cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, HIV: human immune deficiency virus, PML: progressive multifocal leucoencephalopathy, SSPE: subacute sclerosing panencephalitis NP

Multiple Sclerosis

Differential Diagnosis
Tabes dorsalis Familial ataxia Subacute combined degeneration (B12 deficiency) Spinal cord tumor Cervical spondylosis

Multiple Sclerosis

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Neuromyelitis Optica Diagnosis

Absolute criteria: Optic neuritis + acute myelitis No clinical disease outside optic-spinal Supportive criteria: Major: negative brain MRI at onset abnormal spinal cord MRI > 3 vertebra CSF > 50 WBC/mm3 or > 5 PMN/mm3 Minor: bilateral optic neuritis severe ON, VA < 20/200 in 1 or 2 eye severe fixed weakness (MRC < 2 in 1 or more limbs
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Wingerchuck et al. Neurology 1999;53:1107-14.

Neuromyelitis Optica Diagnosis

Absolute criteria: Absolute criteria: Optic neuritis + acute myelitis Supportive criteria: Optic neuritis + acute myelitis No clinical disease outside optic-spinal Supportive Major: criteria: No clinical disease outside Major: Supportive criteria: negative brain negative brainMRI at onset optic-spinalMRI at onset Minor: abnormal spinal cord MRI > 3 vertebra abnormal spinal MRI 5 PMN/mm3 CSF > 50 WBC/mm3 or > > 3 vertebra bilateral optic neuritis Minor:>50 WBC or >5 CSF bilateral optic neuritis PMN per mm3 severe ON, VA< 20/200 in 1 or 2 eye severe ON, VA < 20/200 in 1 or 2 eye severe fixed weakness (MRC(MRC < more severe fixed weakness < 2 in 1 or 2 limbs in 1 or more limbs
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Wingerchuck et al. Neurology 1999;53:1107-14.

Definite NMO: Definite NMO: Optic neuritis Optic neuritis acute myelitis acute myelitis Supportive criteria: 2 in 3 Supportive criteria: 2 in 3 Brain MRI not compatible with Barkhofs criteria Brain MRI not compatible with Spinal MRI > 3 vertebral body segments Barkhofs criteria NMO IgG antibody positive Spinal MRI > 3 vertebral body segments NMO IgG antibody positive
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Neuromyelitis Optica Diagnosis

Wingerchuck et al. Neurology 2006;66:1485-9.

Multiple Sclerosis
Scope: Clinical manifestations Pathology Pathogenesis Diagnosis Treatment
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Multiple Sclerosis

Treatment
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Multiple Sclerosis Treatment

Acute relapses Disease modifying therapies (DMT) Symptom control

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Multiple Sclerosis Treatment

Acute relapses Disease modifying therapies (DMT) Symptom control

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Multiple Sclerosis Acute Relapses Rx

1. Glucocorticoids Rational: - Inhibit synthesis and transport of MMP - Alter cytokine profiles - Reduce brain edema Rx: methylprednisolone 1 g in NSS 100 ml iv drip for 3-5 days then prednisolone: po tapering in 11 days
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Frohman EM, et al. N Eng J Med 2006;354:942-55

Multiple Sclerosis Acute Relapses Rx

2. Plasma exchange Rational: To remove circulating autoantibodies, compliments Indication: Severe steroid-resistant relapses, neuromyelitis optica (NMO), acute disseminated encephalomyelitis (ADEM) within 1 month of onset of symptom
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Kieseier BC, et al. Curr Opion Neurol 2007;20:286-93

Multiple Sclerosis Acute Relapses Rx

2. Plasma exchange Rx: 1 plasma volume 7 exchanges alternate day

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Kieseier BC, et al. Curr Opion Neurol 2007;20:286-93

Multiple Sclerosis Treatment

Acute relapses Disease modifying therapies (DMT) Symptom control

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Multiple Sclerosis Disease Modifying Therapy

Disease modifying therapies DMT
1. Interferon beta 2. Glatiramer acetate 3. Mitoxantrone 4. Monoclonal antibodies 5. Oral therapies
De Angelis T, Lublin F. Curr Opion Neurol 2007;20:261-71 Costello FC, Stuve O, Weber M, et al. Curr Opion Neurol 2007;20:281-5 Kieseier BC, Weindl H, Hemmer B, et al. Curr Opion Neurol 2007;20:286-93

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Multiple Sclerosis Disease Modifying Therapy

1. Interferon beta IFN
Mechanism: Anti-inflammatory effect by - inhibit cytokine production - limit access of immune cell infiltration to CNS

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De Angelis T, Lublin F. Curr Opion Neurol 2007;20:261-71 Costello FC, Stuve O, Weber M, et al. Curr Opion Neurol 2007;20:281-5 Kieseier BC, Weindl H, Hemmer B, et al. Curr Opion Neurol 2007;20:286-93

Multiple Sclerosis Disease Modifying Therapy

1. IFN 1
Type Drug RebifR Company
Biogen Idec Merck Serono Pharma

g
30 22, 44 250

Route Dose IM Sc Sc 1/wk 3/wk AD

IFN 1a AvonexR

IFN 1b BetaseronR Bayer Schering

IM: intramuscular, Sc: subcutaneous, wk: week, AD: alternate day

De Angelis T, Lublin F. Curr Opion Neurol 2007;20:261-71 Costello FC, Stuve O, Weber M, et al. Curr Opion Neurol 2007;20:281-5 Kieseier BC, Weindl H, Hemmer B, et al. Curr Opion Neurol 2007;20:286-93

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Multiple Sclerosis Disease Modifying Therapy

2. Glatiramer acetate (Copolymer-1)
Mechanism: Anti-inflammatory effect by - induce changes in phenotypic expression of T helper cell - modify central effects of inflammation

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De Angelis T, Lublin F. Curr Opion Neurol 2007;20:261-71 Costello FC, Stuve O, Weber M, et al. Curr Opion Neurol 2007;20:281-5 Kieseier BC, Weindl H, Hemmer B, et al. Curr Opion Neurol 2007;20:286-93

Multiple Sclerosis Disease Modifying Therapy

3. Mitoxantrone
Mechanism: - reduce Th1 cytokines - eliminate lymphocytes Indication: SP MS, PR MS, refractory RR MS
De Angelis T, Lublin F. Curr Opion Neurol 2007;20:261-71 Costello FC, Stuve O, Weber M, et al. Curr Opion Neurol 2007;20:281-5 Kieseier BC, Weindl H, Hemmer B, et al. Curr Opion Neurol 2007;20:286-93

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Multiple Sclerosis Disease Modifying Therapy

4. Monoclonal antibodies
Mechanism: Targeted therapies of molecules involved in pathogenesis

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De Angelis T, Lublin F. Curr Opion Neurol 2007;20:261-71 Costello FC, Stuve O, Weber M, et al. Curr Opion Neurol 2007;20:281-5 Kieseier BC, Weindl H, Hemmer B, et al. Curr Opion Neurol 2007;20:286-93

Multiple Sclerosis DMT: Monoclonal Antibody

Type Drug
TysabriR

Company
Biogen Idec Bayer Schering Pharma Biogen Idec

Target

Natalizumab

-4 integrins
CD52 NK, B cell CD20 B cell CD25, IL 2

Alemtuzumab CampathR Rituximab Daclizumab

MabTheraR Roche ZenapaxR

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De Angelis T, Lublin F. Curr Opion Neurol 2007;20:261-71 Costello FC, Stuve O, Weber M, et al. Curr Opion Neurol 2007;20:281-5 Kieseier BC, Weindl H, Hemmer B, et al. Curr Opion Neurol 2007;20:286-93

Multiple Sclerosis Disease Modifying Therapy

Disease modifying therapies DMT
1. Interferon beta 2. Glatiramer acetate 3. Mitoxantrone 4. Monoclonal antibodies 5. Oral therapies
De Angelis T, Lublin F. Curr Opion Neurol 2007;20:261-71 Costello FC, Stuve O, Weber M, et al. Curr Opion Neurol 2007;20:281-5 Kieseier BC, Weindl H, Hemmer B, et al. Curr Opion Neurol 2007;20:286-93

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Multiple Sclerosis Oral Therapy

5.1 Cladribine 5.2 Fingolimod 5.3 Fumaric acid ester 5.4 Laquinimod 5.5 Teriflunamide 5.6 Glatiramer acetate 5.7 statin
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(Merck Serono) (Novartis) (Biogen Idec) (Teva Neurosci.) (Sanofi Aventis) (Teva Neurosci.)

De Angelis T, Lublin F. Curr Opion Neurol 2007;20:261-71 Costello FC, Stuve O, Weber M, et al. Curr Opion Neurol 2007;20:281-5 Kieseier BC, Weindl H, Hemmer B, et al. Curr Opion Neurol 2007;20:286-93

Multiple Sclerosis Treatment

Acute relapses Disease modifying therapies (DMT) Symptom control

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Multiple Sclerosis Symptom Control

Weakness Spasticity Pain Fatigue Psychological disorders

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Multiple Sclerosis Symptom Control

Weakness Rehabilitation: increase strength increase endurance

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Multiple Sclerosis Symptom Control

Spasticity Exercise Massage Central muscle relaxant: baclofen, tizanidine Botulinum toxin injection
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Multiple Sclerosis Symptom Control

Pain neuropathic pain - antidepressant: TCAs, SSRIs - anticonvulsant: carbamazepine, gabapentin, oxcarbazepine, pregabalin
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Multiple Sclerosis Symptom Control

Pain tonic spasm: spontaneous, action - behavior adjustment: slow, steady movement - antidepressant: TCAs, SSRIs - central muscle relaxant: baclofen, tizanidine
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Multiple Sclerosis Symptom Control

Fatigue: feeling lack of energy - not weakness or depressive mood - improve with exercise - balance between rest and exercise - keep cool while exercise

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Multiple Sclerosis Symptom Control

Psychological disorders: Depressive mood - psychological support - antidepressant: TCAs, SSRI Anxiety - psychological support - anxiolytic
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Multiple Sclerosis Treatment

Acute relapses Disease modifying therapies (DMT) Symptom control

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Multiple Sclerosis
Scope: Clinical manifestations Pathology Pathogenesis Diagnosis Treatment in MS
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Case Presentation
Eye: A young woman had dimmed vision of the left eye for 2 days. Eye drop tried without improvement. Vision got worse. Pain on eye movement was noted. Diagnosis: optic neuritis Rx: high dose steroids
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Case Presentation
ENT: A young woman felt spinning for Few days later she had double a few days, getting worse with vision, nystagmus and ataxia. motion. There was no hearing loss MRI: brainstem lesion or visual blurring. Diagnosis: clinically isolated synd. Rx: high dose steroids
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Case Presentation
Urology: A young woman difficulty in One day later she developed voiding for 3 days. numbness and weakness of both Urinalysis: WBC 3-5, RBC 5-10, few legs. bacteria LP: h WBC MRI: intrinsic cord lesion T level Diagnosis: acute myelitis d NP

Case Presentation
GI: A young woman had nausea and Past history: 5 days.loss had very vomiting for visual He (optic frequent hiccoughs for 1 day. neuritis) left eye EGD: showed mild gastritis Rx: iv methylprednisolone (MP)
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Case Presentation
Orthopedics: A middle age woman had gait Rx: laminectomy difficulty 2-3 weeks. She could not properly lift her feet above the Few months later she had bilateral ground. There was some numbness visual loss. at the lower legs. Dx: RR MS Diagnosis: lumbar spondylosis CT myelogram: disc herniation
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Case Presentation
Skin: A middle age man experienced Few weeks later he had numbness itching at the anterior chest left side at the left chest down to the left for 1 week. No rash was noted. leg and weakness of both legs. MRI: intrinsic cord lesion Rx: IV MP dermatitis Diagnosis: Rx: topical steriods
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Case Presentation
Surgery: A middle age woman had headache for 1-2 months. She could Brain biopsy: chronic demyelination not do her routine work, was slow in response. Mild weakness was noted. Inx: CT brain with contrast -mass Diagnosis: brain tumor
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Q&A

MS
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Acute Optic Neuritis Investigations

1. Demonstrate the lesion Optic nerve MRI, VEPs 2. Look for other site involved Brain, whole cord MRI, CSF oligoclonal bands 3. Look for other causes Immune profile, (anti HIV)

d NP

Acute Myelitis Investigations

1. Demonstrate the lesion Whole cord MRI 2. Look for other site involved Brain MRI, VEPs, CSF oligoclonal bands 3. Look for other causes Immune profile, (anti HIV)

d NP