Neuroinflammatory Disorders

Question 1

What are the components of the immune system?

Answer 1

-Innate defences
= Surface barriers (skin, mucosal membranes)
=Internal defences (phagocytes, fever, NK cells, antimicrobial proteins, inflammation)
-Adaptive defences
=Humoral immunity (B cells)
=Cellular immunity (T cells)

Question 2

What is inflammation of the meninges?

Answer 2

Meningitis
=Bacterial
=Viral
=Fungal
=Parasite
=Non-infectious/ Aseptic (tumour, drugs, surgery)

Question 3

What are the equivalents of phagocytes?

Answer 3

Macrophages and microglia

Question 4

What are the roles of the microglia?

Answer 4

• Survey cellular environment
• Promote repair
• Synaptic pruning and regulation
• Neurotrophism
• Release proteases and ROS

Question 5

What are the negative consequences of microglia?

Answer 5

Microglia can cause trouble in chronic CNS 
     inflammatory states (e.g. progressive MS)

 Implicated in everything from 
 depression to dementias

     No treatments (yet) for these conditions 
     based on microglial-targeted therapies

Question 6

Describe Uhthoff’s phenomenon

Answer 6

Decompensation of damaged NS- symptoms worsen
Seen in MS/ chronic CNS issues
Optimal conditions cooler

Question 7

Why does diffuse inflammation affect the CNS?

Answer 7

Neurotransmitters/ neuromodulators
Present unregulated= impaired neuronal function
-Delirium
-Inflammatory cascade/ infectious states

Question 8

Autoimmune disease that affects the nerves

Answer 8

Guilian Barre syndrome

Question 9

Autoimmune disease that affects the NMJ

Answer 9

Myasthenia Gravis

Question 10

What is MS?

Answer 10

Chronic inflammatory and degenerative disease of the central nervous system

Question 11

How is MS characterised pathologically?

Answer 11

Inflammation
Demyelination ± variable extent of remyelinating
Neuroaxonal injury/loss
Astrogliosis= scarring due to proliferation of astrocytes

Question 12

Describe MS epidemiology in Scotland

Answer 12

Scotland has high prevalence
Aukney has highest prevalence
8.6 per 100K per annum
-Incidence increases the further north you travel
(less aggregate sunlight)
-Longitudinal= west is higher= rains much more
-3:1 F:M
-Peak incidence at 40.8 years

Question 13

What are the risk factors for MS?

Answer 13

-Genetics
-Environment
=Vitamin D
=Smoking
=EBV
=Obesity

Question 14

What are the triggers for MS?

Answer 14

EBV
Other pathogens
Idiopathic

Question 15

What amplifies MS?

Answer 15

Sustain the immune system

Bacteria microbiome in gut

Question 16

What are the clinical features of MS?

Answer 16

• Relapsing-remitting stage
• Relapsing with persistent deficits
• Progressive stage

Question 17

What are the types of MS?

Answer 17

Relapse Remitting MS
Secondary Progressive MS (next phase)
85%
Primary Progression MS= 15%

Question 18

How do we diagnose MS?

Answer 18

Criteria= Macdonald
No test for MS
Diagnosis of exclusion
Dissemination in space and time= separation in neuroanatomical space (present in different places at different times)
MRI
Lumbar puncture

Question 19

What do we see on an MRI scan with MS?

Answer 19

T2 weighted
-Patches of increased signal in white matter around ventricles
=Gliosis in white matter
Acute lesion= leaky BBB to yell dissemination in time (not MRI)

Question 20

How can we test the CSF?

Answer 20

Dissemination in time
= IgG oligoclonal bands (non specific antibodies in CSF, generally not there)- persistent leakiness so multiple diffuse
=Compare to serum
=If CSF has more than serum, hasn’t just leaked in from blood

Question 21

What are the treatments of MS?

Answer 21

Relapse= immuno modulator and immunosuppressant= disease modifying therapies
Efficacy vs safety
Induction and maintenance approach
Escalation approach (mild to strong)

Question 22

Describe the pathobiology of progressive MS

Answer 22

• Inflammatory disease activity
• Relapse driven by local BBB leakage
• Diffuse activation of microglia
• Neuroaxonal resilience/ vulnerability
• Remyelinating capacity