Multiple sclerosis

Question 1

What is multiple sclerosis?

Answer 1

MS is a chronic autoimmune T-cell mediated inflammatory disorder of the CNS

Multiple plaques of demyelination occur throughout the brain and spinal cord, occurring sporadically over years

Question 2

What affect does MS have on neural conduction?

Answer 2

The multiple plaques of demyelination disrupt the ability of parts of the nervous system to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems

Question 3

What is a strong environmental factor in developing multiple sclerosis?

Answer 3

Strong north-south divide → more cases further from the equator

Question 4

What age does multiple sclerosis usually present?

Answer 4

Presentation is typically between 20 and 40 years of age.

Presentation after age 60 is rare although diagnosis may sometimes be much delayed, occurring years after initial symptoms.

Question 5

What is the pathophysiology of multiple sclerosis?

Answer 5

T cells gain entry into the brain via disruptions in the blood–brain barrier. The T cells recognize myelin as foreign and attack it, explaining why these cells are also called “autoreactive lymphocytes”

A repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes are unable to completely rebuild the cell’s myelin sheath

Question 6

What are the three pathological characteristics of multiple sclerosis?

Answer 6

1. Lesions in the central nervous system (also called plaques)
2. Inflammation
3. Destruction of myelin sheaths of neurons

Question 7

What are risk factors for multiple sclerosis?

Answer 7

1. Genetic susceptibility (HLA and MHC polymorphisms)
2. Viral infections can precipitate MS, especially EBV and Human herpesvirus 6

Exposure to infectious agents in childhood may reduce risk of developing MS and other autoimmune disorders

Question 8

What viral infections can trigger multiple sclerosis?

Answer 8

EBV

HHV-6

Question 9

What is the clinical presentation PATTERN of multiple sclerosis?

Answer 9

The course of symptoms occurs in two main patterns initially

1. Episodes of sudden worsening that last a few days to months (called relapses, exacerbations, bouts, attacks, or flare-ups) followed by improvement (85% of cases)
2. Gradual worsening over time without periods of recovery (10–15% of cases)

Question 10

What is the clinical presentation of multiple sclerosis?

Answer 10

1. Clumsy/useless hand or limb – due to loss of proprioception (often a dorsal column spinal plaque)
2. Sensory symptoms – often unusual, e.g. sensation of water trickling down skin
3. Fatigue
4. Cognitive impairment
5. Vision problems
6. Problems with thinking, learning, planning, talking, swallowing
7. Muscle weakness, mobility problems
8. Muscle spasms, stiffness, pain

Question 11

How is multiple sclerosis diagnosed?

Answer 11

Few other neurological diseases have a similar relapsing and remitting course. The diagnosis of MS requires two or more attacks affecting different parts of the CNS

History and support from investigations, particularly MR imaging, make the diagnosis

Question 12

How do you manage multiple sclerosis?

Answer 12

There is no cure for MS but in recent years several immunomodulatory treatments for MS have been introduced

1. General measures include education and treatment for symptoms
2. For acute relapses, steroids (IV methylprednisolone 1 gram/day for 3 days) can be used to aid recovery
3. Immunomodulatory drugs such as β-interferon (both INF-β1b and 1a) and glatiramer acetate reduce relapse rate by one-third

Question 13

How do you administer disease-modifying drugs in multiple sclerosis?

Answer 13

They are self-administered by s.c. or i.m. injection and are generally well tolerated apart from flu-like side-effects and injection site irritation

Question 14

In severe relapsing-remitting multiple sclerosis, what do you do?

Answer 14

In severe relapsing-remitting MS, immunomodulatory drugs and biological agents (monoclonal antibodies) such as natalizumab, alemtuzumab and oral fingolimod have shown high efficacy in preventing relapses and may reduce accumulation of disability significantly

Question 15

What is the prognosis for multiple sclerosis?

Answer 15

The clinical course of MS is unpredictable: a high MR lesion load at initial presentation, high relapse rate, male gender and late presentation are poor prognostic features but not invariably so.

Many patients continue to live independent, productive lives; a minority become severely disabled. Life expectancy is reduced by 7 years on average

Question 16

What do you know about the lesions in multiple sclerosis?

Answer 16

2–10 mm in size

MRI studies show that most inflammatory plaques are asymptomatic.

Peripheral myelinated nerves are not directly affected in MS

Acute relapses are caused by focal inflammation-causing myelin damage and conduction block

Progressive axonal damage is the pathological basis of the progressive disability seen in progressive forms of MS