2. Learning Objectives
Define multiple sclerosis
Describe the pathophysiology of multiple sclerosis
Describe the risk factors and etiology of multiple sclerosis
Discuss the classification of multiple sclerosis
Discuss the clinical features of multiple sclerosis
Justify the laboratory investigations advised for multiple sclerosis
Discuss the management of multiple sclerosis
List the complications of multiple sclerosis
3. Introduction; Definitions
An inflammatory disease in
which the fatty myelin sheaths
around the axons of the brain
and spinal cord are damaged,
leading to demyelination and
scarring as well as a broad
spectrum of signs and
symptoms
4.
5. Etiology
It is a disease of young adults
Mostly between age of 20 & 40 years
Females are affected more than males.
Cause of disease is unknown; may interplay between a viral infection, host immune response &
hereditary alone or in combination.
Breach in blood brain barrier in genetically predisposing individual would be responsible for MS
9. Triggers that exacerbate MS
Since raising the temperature shortens the duration of action potential
One of the early signs is improvement on cooling and worsening by hot bath.
Infections or trauma may acutely worsen the disease.
Pregnancy especially the 2 to 3 months following birth.
12. Investigations
MRI of the brain is the most accurate test to diagnose MS, reaching a sensitivity of 85 to 95% in
symptomatic persons.
Increased T2 and decreased T1 intensity represent the increased water content of demyelinated
plaques in the cerebrum and spine.
Enhancement of lesions with gadolinuim indicates active MS lesions that may enhance for up to
2 to 6 weeks after an exacerbation.
14. Multiple high-signal lesions in para-
ventricular region on T2 image
T1 image with gadolinium enhancement:
Recent lesions (A) show enhancement,
suggesting active inflammation
(enhancement persists for 4 wks)
Older lesions (B) show no enhancement
but low signal, suggesting gliosis
15. Evoked potentials
EP testing assesses function in afferent (visual, auditory, and somatosensory) or efferent (motor)
CNS pathways
Computer based measurement of CNS electric potentials evoked by repetitive stimulation of
selected peripheral nerves or of the brain
Most informative when the pathways are clinically uninvolved
16. Evoked potential response
Evoked response potentials detect slow or abnormal conduction in response to visual, auditory
or somatosensory stimuli.
The limitations of this test for the diagnosis of MS is that many other neurologic diseases can
give an abnormal result.
17. Cerebrospinal fluid
CSF abnormalities found in MS:
◦ Mononuclear cell pleocytosis
◦ Increased level of intrathecally synthesized IgG
◦ Total CSF protein is usually normal or slightly elevated
Oligoclonal banding (OCB) in CSF also assesses
intrathecal production of IgG
Two or more OCBs are found in 75 to 90% of patients
with MS
21. Treatment of Multiple Sclerosis
Although no cure exists for MS, treatment aims to reduce the number of relapses or attacks and
to lessen their severity when they do occur.
◦ Treatment of Acute attack
◦ Disease modifying drugs
◦ Treatment of associated symptoms/complications
22. Treatment of acute attack
Steroids: methylprednisolone (MP) 500–1,000 mg/d IV for 5 days followed by tapered oral
prednisone or MP 1 g/d IV for 3 days
± oral taper
23. Disease modifying treatment
Six treatments have been approved by FDA
1. Interferon beta-1a (Avonex, CinnoVex,ReciGen and Rebif)
2. Interferon beta-1b (Betaseron )
3. Glatiramer acetate (Copaxone), a non-steroidal immunomodulator
4. Mitoxantrone, is an immunosuppressant
5. Natalizumab (Tysabri)
6. Fingolimod (Gilenya)
The interferons (side effects include flulike symptoms, injection-site reactions, mild liver
dysfunction) and glatiramer acetate are delivered by frequent injections, varying from once-per-
day for glatiramer acetate to once-per-week (but intra-muscular) for Avonex. Natalizumab and
mitoxantrone are given by IV infusion at monthly intervals.
25. Multiple sclerosis in pregnancy
Counselling: provision of pre-conception counselling is best practice.
Relapse risk: endocrine effects on the immune system ensure that relapse risk drops during
pregnancy.
Disease-modifying drugs: risk of teratogenicity means that all disease-modifying drugs should
ideally be stopped
6–8 wks before conception and recommenced after breastfeeding has stopped.
Post-partum relapse rate: rebound of immune system activity means that the highest risk of
relapse is in the 1st year after delivery.
26. Neuromyelitis optica (NMO)
Neuromyelitis optica is the occurrence of transverse myelitis and bilateral optic neuritis
NMO is also known as:
◦ Neuromyelitis optica spectrum disorder
◦ Devic's disease
Spinal MRI scans show lesions that are typically longer than three spinal segments (unlike the shorter lesions of MS)
Clinical deficits tend to recover less well than in MS, and the disease may be more aggressive with more frequent relapses
Treatment with older immunosuppressive agents, such as steroids, azathioprine or cyclophosphamide, and/or plasmapheresis
seems to be more effective than in MS.
