0828 - Autoimmunity in the nervous system

Question 1

What is MS?

Answer 1

Episodes of demyelination affecting the CNS, characterised by repeated attacks separated by time and location. Typically relapsing-remitting and secondary progressive with attacks, but 10% benign relapsing-remitting and 20% primary progressive.

Question 2

What is Guillan-Barre Syndrome (GBS)?

Answer 2

Post-infectious autoimmune peripheral neuropathy. Pain, progressive weakness including paralysis for up to 4 weeks, then plateau with slow recovery. Most common presentation is ascending paralysis/weakness and pain. Biggest concern is respiratory failure.
If it proceeds past 4 weeks it can progress to chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Question 3

Outline immune activation in MS in the CNS

Answer 3

Autoreactive myelin Th1Th17 are no longer regulated when stimulated by antigens. They express adhesion molecules to blood-brain barrier and penetrate, secreting IFN gamma and IL-17 respectively. They re-encounter myelin and activate microglia. The microglia express MHCII, further promoting T-cells, microglia and PMNs. Ultimately, this all attacks the myelin sheath, leading to lesions.

Question 4

What is the pathogenesis of GBS?

Answer 4

Exposure to infectious illness leads to antigen presentation, and host response. Some of the host response (genetic factors) target myelin or axonal components, leading to axonal loss. This is a self-limiting reaction, and ultimately there is remyelination and axonal regeneration.

Question 5

What are the primary autoimmune diseases that can affect the CNS and PNS?

Answer 5

CNS - MS, Connective tissue (e.g. SLE, Sjorgrens), CNS vasculitis, Sarcoidosis
PSN - Guillain-Barre, Connective tissue (RA, SLE, Sjorgrens), PNS vasculitis, infections (Lyme)

Question 6

What are some presenting symptoms of MS?

Answer 6

Optic Neuritis 1/3
Sensory symptoms 1/3 
Motor deficit 1/10
Cerebellar syndromes - ataxia/dysarthria
Brainstem and Diplopia
Transverse myelitis - characteristic of MS
Fatigue.

Question 7

How do you diagnose MS?

Answer 7

MRI demonstrating Multiple lesions, changing with time or enhancing/not enhancing on imaging.
Two or more episodes of demyelination symptoms, at least 30 days apart, and in different sites in the CNS.

Question 8

What are some presenting symptoms in GBS?

Answer 8

Ascending paralysis most common presentation.
Occurs after infection, particularly viral or gastro (campylobacter).
Reflexes lost in 90%
Present with pain and weakness. 50% have facial nerve involvement (mostly bilateral).

Question 9

How do you diagnose MS?

Answer 9

MRI - progressive white matter lesions
CSF - oligoclonal bands - IgG in CSF and good to exclude mimics
Evoked potentials test demonstrating slowed CNS conductivity.

Question 10

How do you diagnose GBS?

Answer 10

History - post-infectious, short term (weeks-months)

CSF - High protein and oligoclonal bands but WCC less than 10.