Neurology: Demyelinating Diseases

Question 1

What is multiple sclerosis (MS)?

Answer 1

Chronic, progressive autoimmune demyelinating CNS disease characterised by neurological dysfunction in at least two areas of CNS separated in time & space

“Immune system attacks myelin of myelinated neurones in CNS causing neurological dysfunction in at least two areas of CNS separated in time & space”

Question 2

At what age, and in what gender, does MS most commonly present?

Answer 2

Females <50yrs (most commonly aged 20-40yrs)

NOTES; symptoms often improve in pregnancy and post-partum period

Question 3

State some risk factors/potential causes for MS

Answer 3

• Genetics/FH
• EBV
• Smoking
• Low vit D
• Obesity

Question 4

Describe the pathophysiology of MS

Answer 4

• Immune system attacks myelin of myelinated neurones in CNS (remember oligodendrocytes produce myelin in CNS)
• When pt’s present with an attack of MS, there is often demyelination in other areas of CNS at same time which is not causing symptoms
• In early stages, re-myelination can occur and symptoms can resolve

Question 5

What is the key term to remember when describing the way MS lesions change location over time?

Answer 5

Disseminated in time and space

Question 6

MS can present in a variety of ways; discuss how MS may present

Answer 6

Symptoms tend to progress over >24hrs and at first tend to last days-weeks and then improve. Can present with:

• Non-specific features/general symptoms e.g. 75% lethargy
• Eye problems
  
  • Optic neuritis
  • Diplopia
  • Oscillopsia (visual disturbance in which objects in the visual field appear to oscillate)
• Sensory problems
  
  • Paraesthesia
  • Anaesthesia
  • Trigeminal neuralgia
  • Lhermitte’s signs (electric shock down spine and into legs when flexing neck)
• Motor problems
  
  • Bell’s palsy
  • Horner’s syndrome
  • Spasticity (often in legs)
  • Weakness
  • Hyperreflexia (UMN lesions)
  • Tremor
• Ataxia
  
  • Sensory
  • Cerebellar
• Other:
  
  • Urinary symptoms (frequency or retention)
  • Constipation
  • Sexual dysfunction
  • Cognitive decline

*Use idea of where lesion is to help you think about what symptoms and vice versa

Question 7

Internuclear ophthalmoplegia can occur in MS, discuss:

• What you see
• Where pathology is and why you see the above

Answer 7

Lesion in medial longitudinal fasciculus in brainstem. This connects CNVI to CNIII. MLF is responsible for coordinated conjugate lateral gaze. E.g. when you want to look to the left abducens (CNVI) signals for the left lateral rectus to contract to abduct the left eye. At same time, signals are sent to the contralateral CNIII nucleus via MLF to cause the right oculomotor nerve to signal for the right medial rectus to contract to adduct the right eye. Damage to MLF disrupts this coordination resulting in:

• Nystagmus of contralateral/abducting eye
• Impaired adduction of ipsilateral eye

Question 8

What does Lhermitte’s sign indicate/where does it indicate the pathology is?

Answer 8

Disease in the dorsal columns of cervical spinal cord

Question 9

Pts with MS may also have Uhthoff phenomenon; what is this?

Answer 9

Worsening of neurological symptoms that occur with elevated body temperature (e.g. exercise or hot bath)

Question 10

State the three subtypes of MS

Answer 10

• Relapsing-remitting
• Secondary progressive
• Primary progressive

Question 11

Describe relapsing-remitting MS

Answer 11

• Most common pattern at diagnosis
• Episodes of disease/neurological symptoms then recovery
• Can be further classified into:
  
  • Active: new symptoms are developing or new lesions are appearing on MRI
  • Not active: no new symptoms or MRI lesions are developing
  • Worsening: there is an overall worsening of disability over time
  • Not worsening: there is no worsening of disability over time

Question 12

Describe secondary progressive MS

Answer 12

• MS was relapsing-remitting at first but now there is progressive worsening of symptoms with incomplete remissions (occurs in around 65% of those with r-r MS)
• Can be further classified:
  
  • Active: new symptoms are developing or new lesions are appearing on MRI
  • Not active: no new symptoms or MRI lesions are developing
  • Progressing: there is an overall worsening of disease over time (regardless of relapses)
  • Not progressing: there is no worsening of disease over time

Question 13

Describe primary progressive MS

Answer 13

• Worsening of symptoms & disease from diagnosis without initial relapses and remissions
• Can be further classified same as secondary progressive:
  
  • Active: new symptoms are developing or new lesions are appearing on MRI
  • Not active: no new symptoms or MRI lesions are developing
  • Progressing: there is an overall worsening of disease over time
  • Not progressing: there is no worsening of disease over time

Question 14

What are paroxysmal symptoms of MS?

Answer 14

Paroxysmal is a term that describes the way that some symptoms of multiple sclerosis come on very suddenly, last only a few seconds or minutes and then disappear just as quickly. Sometimes this cycle repeats a few times or, perhaps, many times in a day. Paroxysmal symptoms, involving unusual sensations or muscular contractions, are relatively unique to MS and are sometimes confused for seizures that occur with epilepsy Examples:

• Trigeminal neuralgia
• Lhermitte’s phenomenon
• Spasms
• Weakness
• Shooting pains
• Altered sensation
• Akinesia

Question 15

What is clinically isolated syndrome (in regards to MS)?

Answer 15

• First episode of neurological symptoms & signs due to demyelination
• Can’t diagnose MS if only had one episode as not “disseminated in time & space”
• Might never develop MS but if lesions on MRI then more likely to develop MS

Question 16

How is MS diagnosed?

Answer 16

Diagnosed clinically based on symptoms and the idea that lesions change location over time “disseminated in space & time”. To diagnose primary progressive MS symptoms must be progressive for at least 1yr.

Investigations to support diagnosis:

• MRI (with contrast) brain & spinal cord
• Immunoelectrophoresis of CSF from lumbar puncture: oligoclonal bands of IgG

Question 17

MS can present with optic neuritis; however, there are many other potential causes of optic neuritis. What % of people, approximately, with a single episode of optic neuritis will go on to develop MS over next 15yrs?

Answer 17

~50%

Question 18

Discuss the management of MS

Answer 18

Managed by MDT. Treatment focused on reducing frequency and duration of relapse. Options for treatment include:

• Treatment for disease modification/reducing relapses:
  
  • Disease modifying/immunomodulating/biologics drugs
    
    • Natalizumab (monoclonal antibody that inhibits leucocytes across blood brain barrier. IV. Passmed says strongest evidence based so often first line)
    • Fingolimod (PO)
    • Beta interferon
• Treatment for relapses:
  
  • Methylprednisolone 500mg PO for 5/7
  • Or 1g IV daily for 3-5/7 (if oral treatment failed or severe)
• Symptomatic treatments:
  
  • Spasticity: baclofen, gabapentin, physiotherapy
  • Fatigue: rule out other causes (e.g. anaemia, hypothyroid, depression) if not offer amantadine. Other options include mindfulness training & CBT
  • Paroxysmal symptoms: low dose anticonvulsants e.g. carbamezapine, valporic acid
  • Neuropathic pain: medications e.g. amitriptyline, gabapentin
  • Oscillopsia: gabapentin
  • Depression: antidepressants
  • Urinary symptoms (urgency, incontinence, overflow): US to assess bladder emptying. If significant residual volume consider intermittent self-catheterisation. If no significant volume consider anticholinergics e.g. oxybutynin (but may worsen cognition), intermittent self catheterisation if retention
  • Weakness: exercise, physiotherapy

NOTE: steroids for relapses shorten recovery they do not alter degree of recovery

Question 19

MS most commonly affects young women hence being aware of impact of MS on pregnancy is important; discuss:

• How pregnancy may affect a pt with known MS
• What advice would you give to woman with MS who is contemplating pregnancy

Answer 19

Pregnancy affect MS and vice versa

• MS has no impact on fertility
• Pts with MS no more likely to have miscarriage or birth defects
• If have R-R, less likely to have relapse during pregnancy but there is increased risk of relapse in first 6 months after birth (due to changes in hormones)
• Pregnancy has no adverse effects on MS in the long run
• There is an increase chance of baby having MS but this is still low (most pts with MS have no FH)

Advice

• Number of DMARDs not suitable for use in pregnancy or breast feeding therefore consult with MS nurse or doctor

Question 20

What is Guillian Barre Syndrome (GBS)?

Answer 20

Acute, immune-mediated inflammatory polyneuropathy (immune system attacks the peripheral nervous system). Often triggered by a recent infection. It is classified according to symptoms and can be split into axonal and demyelinating forms. Most common variant is acute inflammatory demyelinating polyradiculopathy.

Question 21

GBS is usually triggered by an infection; state 3 infective organisms it is associated with

Answer 21

• Campylobacter jejuni
• Cytomegalovirus
• Epstein-Barr virus

Question 22

Explain the pathophysiology of GBS

Answer 22

Due to “molecular mimicry”

• B cells produce antibodies against antigens on pathogen causing the infection
• The antibodies also match/target protein on nerve cells
• Antibodies can target myelin sheath or the nerve axon

Question 23

Describe typical presentation of GBS (include symptoms & signs)

Answer 23

• Pain (~65% have at the start- particularly in the back & legs)
• Symmetrical ascending weakness (starts at feet & moves up)
• Hyporeflexia/areflexia
• Peripheral paraesthesia (glove & stocking distribution)
• Bulbar dysfunction
  
  • Dysphagia
  • Dysarthria
• Cranial nerve involvement:
  
  • Facial weakness
  • Extra-ocular muscle weakness (15%. May lead to diplopia)
• Respiratory muscle weakness (20-30%)
• Dysautonomia
  
  • Tachycardia
  • Hypertension
  • Postural hypotension
  • Urinary retention
  • Ileus

Question 24

Outline the typical clinical course/progression of GBS

*I.e. when do symptoms start, when do symptoms peak, how long last for etc…

Answer 24

Question 25

What investigations are done for GBS/how is GBS diagnosed?

Answer 25

• Diagnosis is CLINICAL using Brighton criteria
• Investigations can support diagnosis:
  
  • Nerve conduction studies: reduced motor nerve conduction velocity (if demyelination type)
  • LP: raised protein with normal cell count & glucose

Question 26

Discuss the management of GBS

Answer 26

• IV immunoglobulins
  
  • Plasma exchange is an alternative
• VTE prophylaxis
• Supportive care
  
  • Painkillers
  • NG tube
  • Catheter
  • Laxatives if constipated
• If respiratory failure, may need intubation & ventilation in ICU

Question 27

Discuss the prognosis of GBS

Answer 27

• 80% fully recover
• 15% left with some neurological disability
• 5% die

Question 28

What is Miller Fisher syndrome?

Describe typical presentation

What antibodies present in 90% cases? (less important)

Answer 28

• Variant of GBS
• Presentation:
  
  • Descending paralysis
  • Eye muscles typically affected first
  • Associated with ophthalmoplegia, areflexia & ataxia
• Anti-GQB1