Overview of Multiple Sclerosis

Question 1

What is the job of the medial longitudinal fasciculus?

Answer 1

• There are paired occulumotor, trochlear, abducent and vestibular nuclei, each which have communications with the others.
• These communications between the nucleui of CN3, CN4 and CN6 all cross and communicate in the medial longitudinal fasciculus.
• Its function is to coordinate any movement between both eyes so that there is no diplopia.
• The vestibular nuclei are also connected to the medial longitudinal fasciculus, which allows it to know where the body is in space and when necessary can compensate for the position of the head when it is held at a different angle.
  
  • This tells the extraoccular muscles to move in a compensatory fashion so that we can maintain a level horizon.
• All these nuclei also send descending connections into the SC enabling us to generate compensatory movement of the neck or trunk in order to keep us in a neutral position.

Question 2

What happens to the medial longitudinal fasciculus in Multiple Sclerosis?

Answer 2

• When testing for MS you need to test pursuit (follow finger) and voluntary gaze (clicking).
• Medial longitudinal fasciculus is the first pathway to myelinate in man and the first to demyelinate - it is a clinical sign of multiple sclerosis almost exclusively.

Question 3

Describe the role of the nodes of ranvier.

Answer 3

• Increase the rate of conduction (saltatory).
• The main sodium channels are located at the node of ranvier (fast depolarisation) and these sodium channels are closely related with astrocytes.

Question 4

What happens in the brain in an attack of RR MS?

Answer 4

• First stage of an episode of MS is that the BBB is breached and cells transfer across and attack.
• This tends to occur around blood vessels (in a periventricular distribution) around venules particularly.
• The repair of the inflammation and disruption of the myelin sheath occurs after an attack of RR MS, but the repaired myelin sheath is of a poorer quality with fewer layers than it was before the attack, so conduction is slowed.

Question 5

What are the common clinical presentations of CIS / MS.

Answer 5

• Optic neuritis - often painful visual blurring / reduction acuity over hours-days, followed by gradual recovery, maybe left with alteration of colour vision.
• Myelitis - sometimes called transverse myelitis, depending on where in spinal cord the lesion is, often ascending numbness with urinary urgency / frequency, maybe motor loss.
• Brainstem - maybe diplopia / balance disturbance / vertigo. Internuclear ophthalmoplegia (INO) virtually pathognomonic of MS.

Question 6

Describe the McDonald Criteria for MS - 2001-2017.

Answer 6

• Evidence for lesions likely due to demyelination.
• Separated in space (disseminated in space).
• Separated in time (disseminated in time).
• Can use MRI as well as cinical lesions.
• If PPMS, at least 12 months of clinical deterioration.
• Exclusion of other conditions (B12, ANF etc.).

Question 7

Desribe the relative prevalence of the different types of MS.

Answer 7

Question 8

Describe the prevalence of MS in different age groups.

Answer 8

Question 9

What is the genetic component of risk of developing MS?

Answer 9

• 30% genetic component in this condition.
• There are >150 genes which are associated with MS.
• Major on chromosome 6 which controls MHC.
• Purple box = chromosome 6 where there is a massive spike associated with MHC.

Question 10

What is the role of vitamin D in MS?

Answer 10

• Vitamin D deficiency and susceptibility to MS
  
  • ​Prospective studies have shown that vitamin D deficiency prior to MS onset predisposes individuals to increased risk of MS (geograpy and sunlight study; Munger et al., 2004; 2006).
• Vitamin D levels and disease activity in RRMS
  
  • ​For every 10ng/mL increase in baseline vitamin D level there was a 34% decrease in rate of subsequent relapse (Mowry et al., 2010).
• Vitamin D supplementation and disease activity in RRMS
• Vitamin D as an immunomodulator

Question 11

Give a summary of the evidence which exists for the aetiology of MS.

Answer 11

• Virtually all subjects with MS (>99%) are infected with EBV compared to only ~90% of control subjects.
• MS is very rare in subjects who are not infected ith EBV.
• People with MS have an increased tendency to spontaneous in-vitro lymphocyte transformation in clinically active MS.
• People who have had symptomatic EBV infection or glandular fever have a higher risk of developing MS compared to people who have not had glandular fever.
• People with higher levels of antibodies to EBV have a higher risk of developing MS compared to subjects with low antibody levels.
• An unusual cluster of MS in children attending a school in rural Denmark occurred shortly after an outbreak of glandular fever.
• Oligoclonal antibodies in the spinal fluid of subjects with MS recognise EBV antigens.
• Autoimmune T cells in the circulation of subjects with MS, which are capable of orchestrating an attack on myelin producing cells also recognise EBV.
• Subjects with MS have a higher number of CD8⁺ T cells that recognise EBV than control subjects (proliferation and tetramer).
• During an MS relapse there is preliminary evidence that EBV is actively replicating compared to subjects with stable MS.
• Anti-CD20 therapy may work by suppressing peripheral EBV replication.