Multiple sclerosis - med.swu.ac.th fileOutline • Epidemiology • Pathology & pathogenesis •...

Multiple sclerosis

Monton Wongwandee, M.D.Division of NeurologyFaculty of Medicine

Srinakharinwirot University

MS

• Inflammatory demyelination of CNS neurons• Relapsing‐remitting or progressive course• Dissemination in time & space

Outline

• Epidemiology• Pathology & pathogenesis• Etiology• Clinical manifestations• Clinical course and prognosis• Diagnosis• Treatment• Neuromyelitis optica (Devic’s disease)

Epidemiology

• Female: male = 3:1 (6:1 in Thai)• Age of onset: typically 20‐40 years• Prevalence: increasing at higher latitudes

Orkney Islands250:100,000

Japan6:100,000

Outline


Pathology

• Lesions vary in size (1‐2mm to cms)• Triad

– Inflammation• Perivenular cuffing with T‐cells & MØ

• BBB breakdown– Demyelination– Gliosis (astrocytic proliferation)

• Axonal loss– Major contributor to irreversible neurologic disability

• Heterogeneity

Immunology• Antigen

– Myelin basic protein (MBP)– Myelin oligodendrocyte glycoprotein (MOG)

• Autoreactive T lymphocytes• Humoral autoAb

– B cells– Oligoclonal Ab (intrathecal synthesis)

• Cytokines– IL‐2– TNF‐– IFN‐

• Triggers– URTI (viral)

Pathogenesis

• T lymphocyte activation• BBB breakdown• Lymphocytes infiltration

– T cells (CD4,CD8) macrophage– B cells antibodies, compliments

• Oligodendrocytes & myeline destruction• Gray matter involvement

Outline


Etiology

• Unknown– Genetic– Environment

Genetic

• Caucasians > africans, asians• Polygene• Genetic heterogeneity

Environment

• Geographic– Higher latitudes, sun exposure– Vitamin D deficiency– Immunoregulatory effect

• High socioeconomic status– Delayed initial exposures to infectious agents?

• Remote infection– EBV?

Outline


Clinical manifestations

• Extremely vary – Location: optic n., brain, spinal cord– Onset: abrupt – insidious– Severity: trivial – severe

• Attack from RRMS generally evolve over days to weeks

Anatomical lesions• Optic n.• Oculomotor path

– MLF, PPRF, CN fasciculus• Motor path

– Pyramidal tr.– Root exit zone

• Sensory path– Lateral spinothalamic tr.– Dorsal column– Root entry zone

• Cerebelllar path• Autonomic path• Etc.

http://www.dartmouth.edu/~rswenson/NeuroSci/figures/Figure_19.htmhttp://upload.wikimedia.org/wikipedia/commons/2/26/Gray711.png

Clinical manifestationsSymptom Percent of Cases Symptom Percent of Cases

Sensory loss 37 Lhermitte 3

Optic neuritis 36 Pain 3

Weakness 35 Dementia 2

Paresthesias 24 Visual loss 2

Diplopia 15 Facial palsy 1

Ataxia 11 Impotence 1

Vertigo 6 Myokymia 1

Paroxysmal attacks

4 Epilepsy 1

Bladder 4 Falling 1

Characteristic manifestations

• Intractable hiccup• Intractable vomiting• Intractable itching• Bilateral INO• Bilateral trigeminal neuralgia• Painful tonic spasm• Uhthoff’s symptom (heat sensitivity)

Uhthoff's Phenomenon

• Pseudoexacerbation• Increase in ambient temperature• Fever• Infection• Metabolic abnormalities

Outline


Disability

Time

RRMS

Disability

Time

SPMS

Disability

Time

PPMS

Disability

Time

PRMS

Prognosis• Overall,

– ambulation require assistance in most cases • 80% at 25 years after onset

– Benign variant < 20% (no disability)• Individual,

– Favorable outcome• ON or sensory symptoms at onset• < 2 relapses in the 1st year• Minimal impairment after 5 years

– Poor prognosis• Truncal ataxia• Action tremor• Pyramidal symptoms• Progressive course

Disability

Time

MSCIS

Self remission

Clinically isolated syndrome (CIS)

• Single attack compatible with MS (first demyelinating event)

• Most common: ON, transverse myelitis• Prognosis

– Abnormal brain MRI 10 yr risk ̴ 60%– Normal brain MRI 10 yr risk ̴ 20%

Outline


Dissemination in time and space

Disability

TimeE1 E2

> 1m

signMRIVEP

signMRI

>24hr

Dissemination in time & space

Diagnostic tests

• MRI• Evoked potentials• CSF

MRI

• Characteristics of lesions– Hypersignality in T2,FLAIR image– Gadolinium enhancement (BBB breakdown)– Hyposignality in T1 image (black holes)

• Distribution– White matter, usually no edema– Multifocal lesions involved brain, brain stem, spinal cord

• Periventricular area• Corpus collosum

• Other technic– MTR (magnitization transfer ratio)– MRS (magnetic resonance spectroscopy)

Dawson’s fingers

mypacs.net

http://radiopaedia.org/images/562

Evoked potentials

• Test of function in CNS pathways– Afferent : VEP,BAEP,SSEP– Efferent: motor

• Non‐specific etiology

CSF

• Most are normal• Mild MNC pleocytosis (WBC > 5cells/µL)• CSF total protein normal or slightly increase• Red flags

– WBC > 75 cells/µL– PMN predominate– Protein > 100 mg/dL

Outline


Treatment

• Acute attack• Disease modifying therapy

Acute attack

• Shortening the symptom• Long term effect?• High dose steroid

– Methylprednisolone 500‐1,000 mg/day x 3‐5 days with/without tapering in 2 weeks

• Plasma exchange in selected case that not responding to corticosteroid (no clear benefit)

Disease modifying therapy

• Slow the disease but not stop it!• First choice

– Interferon beta‐1a,1b– Glatiramer acetate

• Natalizumab• Mitoxantrone• Fingolimod

Outline


Neuromyelitis optica(NMO)

Devic’s disease

Clinical manifestations

• ON (unilateral or bilateral)• Myelitis• Days, months or years between attack• Usually not brain stem, cerebellar, cognitive involvement

• Brain MRI is typically normal• OSMS (Optico‐spinal MS) or Asian type MS ?

Pathophysiology

• NMO IgG• Aquaporin 4 (AQP4)

– Water channel at foot process of the perivascularastrocyte

• Necrotizing cavitation

Revised NMO criteria (2006)

NMO IgG positive

Treatment

• Acute attack– Steroid– PE

• Disease modifying therapy ?

Multiple sclerosis - med.swu.ac.th fileOutline • Epidemiology • Pathology & pathogenesis •...

Documents

Transcript of Multiple sclerosis - med.swu.ac.th fileOutline • Epidemiology • Pathology & pathogenesis •...