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Multiple Sclerosis Flashcards

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1
Q

What is multiple sclerosis?

A

Chronic, immune mediated ,inflammatory condition of the central nervous system

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2
Q

The CNS is comprised of..

A

The brain
Brainstem
Spinal cord

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3
Q

Which group of patients is MS most commonly seen in?

A

Young people

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4
Q

What is the pathological hallmark of multiple sclerosis?

A

Demyelination

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5
Q

What is demyelination?

A

Damage to the myelin sheath surrounding neurons

Leads to scarring and secondary neuronal cell loss - irreversible neurological damage

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6
Q

Describe the typical course of MS

A

Relapsing-remitting
Unpredictable in individuals
Progressive disability

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7
Q

Mean age of onset of MS

A

30 years old

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8
Q

Aetiology of MS

A

Unknown- abnormal immune reaction to unknown environmental trigger in genetically predisposed individual

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9
Q

Concordance of MS in twins

A

20-35% in monozygotic twins

Dizygotic 5%

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10
Q

Risk factors for MS

A 
Genetics
Infection - EBV
Geographic latitude - more common further from equator; risk changes at 10 years old
Sunlight exposure - inverse relationship
Obesity during adolescence
Smoking
Female
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11
Q

What cell is responsible for producing the myelin sheath and are destroyed in MS?

A

Oligodendrocytes

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12
Q

What type of cells are oligodendrocytes?

A

Glial cells - support neurons

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13
Q

Pathological process of MS

A

Activation of myelin reactive T lymphocytes
Disruption of BBB
Pro-inflammatory response and cell recruitment in CNS
- B cells, microglia, macrophages
Antibody-mediated response
MS plaques with myelin reactive T cells, B cells and macrophages
Inflammation, scarring and axonal injury (loss)
Clinical manifestation depends on location of plaques

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14
Q

What are microglia?

A

Macrophages of CNS

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15
Q

Classic plaque sites in MS

A 
Optic nerves
Spinal cord
Brainstem
Cerebellum
Juxtacortical white matter
Periventricular white matter
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16
Q

What plaque site gives rise to the most common presenting symptom for MS?

A

Optic nerve - vision blurry.
Optic atrohpy - optic disc pale and small
Examine fundi
Patient may be unaware they had optic neuritis

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17
Q

What presenting symptom can indicate an MS plaque in the brainstem?

A

Opthalmaplegia

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18
Q

What is a relapse in MS?

A

Episode of exacerbation of symptoms followed by period of remission in 90%

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19
Q

Do symptoms resolve in remission phase of relapsing-remitting course of MS?

A

Sometimes

As disease progresses patient may be left with residual damage from relapse

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20
Q

What is primary progressive MS?

A

PPMS
Subtype in 10-15%
Sustained rogression of disease severity from onset
May have periods where disease is not active or non-progressive but no evidence of remission

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21
Q

What is secondary progressive MS?

A

Developed by 50% of patients with relapsing remitting MS after 15 years of onset
Disease course changes with gradual worsening of neurological function. Relapses may still occur but not remission

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22
Q

What is Clinically Isolated Syndrome (CIS) - MS?

A

Describes first clinical episode of MS
No previous evidence of demyelination clinically or on imaging
Oligoclonal bands in CSF may be used to support diagnosis

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23
Q

Three characteristic clinical features of MS

A

Optic neuritis
Lhermitte phenomenon
Internuclear opthalmoplegia

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24
Q

What is lhermitte phenomenon?

A

Uncomfortable electric shock sensation triggered by neck flexion

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25
Signs of internuclear opthalmoplegia (INO)?
Ask patient to look left - left eye nystagmus - right eye cannot adduct
26
Which part of the brainstem is susceptible to demyelination and will result in INO?
Pons
27
Other symptoms of MS common to neurological conditions
Motor weakness Diplopia Gait disturbance Bladder/bowel dysfunction
28
Four groups of clinical manifestations of MS
Visual Motor and coordination Sensory and autonomic Cognitive and psychological
29
What is optic neuritis?
Inflammation of the optic nerve
30
Presenting features of optic neuritis
``` Blurred vision Visual loss Pain - behind eye and on movement Scotoma - partial field loss Poor colour differentiation Relative afferent pupillary defect Optic nerve swelling ```
31
Eye movement disorders typically occur due to lesions of...
The brainstem
32
Which two common eye movement disorders are caused by brainstem lesions?
Abducens palsy | Internuclear opthalmoplegia
33
Demyelination of which tract leads to INO?
Medial longitudinal fasciculus
34
What does the medial longitudinal fasciculus connect?
Abducens nucleus complex with contralateral oculomotor complex
35
In INO if looking to the right, what are the signs in each eye?
Right will abduct, left will remain central
36
In abducens palsy what happens in right eye when looking to the right if the right abducens nerve is affected?
Remains central - cannot abduct
37
What is the prominent motor feature in MS?
Progressive paraparesis and upper motor neuron signs
38
What are upper motor neuron signs?
Spasticity Hyperreflexia Reduced power
39
Motor and coordination abnormalities in MS may present as which syndrome?
Typcial clinical syndrome
40
Which 2 conditions are included in typical clinical syndrome (MS)?
Transverse myelitis | Cerebellar syndrome
41
What is transverse myelitis?
Focal inflammation within the spine Sensory and motor symptoms below level of lesion Can have bladder/bowel involvement Usually sensory level corresponding to the lesion
42
What must be excluded in diagnosis of transverse myelitis?
Compressive pathology eg metastatic cord compression
43
Cerebellar syndrome - symptoms
``` Ataxia Slurred speech Intention tremor Nystagmus Vertigo clumsiness ```
44
Sensory and autonomic symptoms of MS
``` Paraesthesia Pain Heat sensitivity (Uhthoff phenomenon) Sexual dysfunction Bladder & bowel dysfunction ```
45
What is the Uhthoff phenomenon?
Heat sensitivity - MS
46
Cognitive and psychological manifestations of MS
Cognitive impairment Fatigue Depression Memory, attention, concentration
47
How is MS diagnosed?
Primarily clinical - MS attack | Supported by MRI images of scarring or lesions
48
What is an MS attack?
an episode of neurological symptoms that relate to an inflammatory demyelinating lesion. Lasts > 24 hours with or without recovery. Typically sensory disturbances, motor weakness, or visual complaints.
49
How many days must be between MS attacks to count as a separate episode?
More than 30 days
50
Which criteria is used in the diagnosis of MS?
McDonald Criteria
51
Principle of the MacDonald criteria
Demyelinating lesions are disseminated in time and space 2 attacks - disseminated in time 2 lesions - disseminated in space
52
MacDonald criteria for diagnosis of MS
≥2 attacks with objective clinical evidence of ≥2 lesions: MS diagnosed ≥2 attacks but objective clinical evidence for only one lesion: evidence of dissemination in time, but not space. MS diagnosed if dissemination in space shown on MRI or subsequent clinical attack representing new area. Single attack with objective clinical evidence of one lesion: clinically isolated syndrome. MS diagnosed once proof of both dissemination in time and space. Single attack with objective clinical evidence of ≥2 lesions: clinically isolated syndrome. MS diagnosed once proof of dissemination in time.
53
Which scan can be used in correlation with the MRI to diagnose MS?
MRI may be used to show dissemination in time by the simultaneous presence of gadolinium-enhancing and nonenhancing lesions at any time, or by a new gadolinium-enhancing lesion(s) on follow-up MRI Show active lesions, and older lesions
54
Differentials to MS
``` Infection Other demyelinating conditions Malignancy Metabolic disorder Systemic inflammatory conditions - SLE, sarcoidosis ```
55
Condition with similar phenotype to MS
Devic's - Neuromyelitis optica | Neuromyelitis optica spectrum disorders
56
Hallmark of neuromyelitis optica spectrum disorders
Acute attack of bilateral optic neuritis or transverse myelitis
57
How does NMOSD differ to MS?
Conditions similar presentation but more severe in NMOSD
58
What antibody is formed in neuromyelitis optica spectrum disorder?
IgG autoantibody to aquaporin 4 (AQP4)
59
Treatment of NMOSD
Corticosteroids | Plasma exchange for refractory cases
60
Investigations for MS
Bloods Oligoclonal bands on CSF Visual Evoked Response Antibody testing
61
Which blood tests are required in diagnosis of MS?
``` FBC CRP/ESR LFTs, U&Es, Bone profile (calcium) Glucose, HbA1c TFTs Haematinics HIV test ```
62
How is CSF sample acquired and what sample is required alongside CSF to confirm MS diagnosis?
Lumbar puncture Serum sample Oligoclonal bands must be absent in serum, present in CSF
63
Which conditon is diagnosed by identical oligoclonal bands in both the CSF and serum?
Rheumatoid arthritis
64
What does the visual evoked response involve in diagnosis of MS?
Electrical activity measured over the occipital cortex in response to light Assesses evidence of previous asymptomatic episodes of optic neuritis Up to 90% of individuals will have a persistent abnormality on VER following an acute episode at one year.
65
Which 2 antibodies are common to NMOSD and can exclude MS as diagnosis?
Both AQP4 and myelin oligodendrocyte glycoprotein (MOG) antibodies are associated with NMOSD.
66
Three categories of MS management to consider
General care Acute relapses Disease modifying treatment
67
Symptoms targeted in MS treatment
``` Bladder dysfunction Depression Fatigue Spasticity Poor motor function ```
68
How is bladder dysfunction treated in the general management of MS
Anticholinergics - oxybutynin for detrusor overactivity Botulism injection Catheter for urinary retention
69
How is bowel dysfunction treated in the general management of MS
(Constipation, poor evacuation and incontinence) Dietary changes Laxatives Enema
70
How is depression treated in the general management of MS
SSRIs | Duloxetine may be used if co-existing neuropathic pain or fatigue
71
How is fatigue treated in the general management of MS
Non-pharmacological eg physical activity Treat depression Pharm - modafinil
72
How is gait impairment treated in the general management of MS
OT Physio Walking aids, wheelchair
73
How is pain treated in the general management of MS
Amitriptyline , Gabapentin, Pregabilin
74
How is spasticity treated in the general management of MS
Physio Baclofen Botulism
75
Treatment of acute relapse of MS
Steroids: oral methylprednisolone 0.5 g daily for five days, OR Intravenous methylprednisolone 1 g daily for 3-5 days Gastroprotection: proton pump inhibitor Discuss risk/benefit of treatment: particular attention to acute changes in blood glucose and mental health
76
When can recovery from acute relapse be expected after treatment?
2-3 months in most cases | May be residual functional disabilities
77
Aim of disease modifying therapies in MS
Decrease relapse frequency and slow progression
78
Two criteria for initiating DMT in MS
No evidence of non-relapsing progressive MS Sustained disability due to MS: measured on Expanded Disability Status Scale (EDSS). Score should be < 7.0 (i.e. at least ambulant with two crutches).
79
Examples of DMTs in MS
``` Interferon beta Glatiramer acetate Teriflunomide Alemtuzumab Cladribine Natalizumab ```
80
Median time of PPMS and requiring a walking aid
8 years
81
Factors linked to prognosis in MS
Disease type: RRMS better prognosis than PPMS. Most patients with RRMS eventually develop SPMS. Recovery following first attack: incomplete recovery associated with worse prognosis Clinical manifestations at onset: pyramidal, brainstem, and cerebellar symptoms (poor prognosis). Sensory symptoms, optic neuritis (favourable prognosis). Pregnancy: protective during pregnancy. Increased risk of relapse in postpartum period. Imaging: lesion load and cerebral atrophy linked to prognosis (higher burden and increased atrophy have worse prognosis).
82
Which disease type of MS has better prognosis?
Relapsing remitting MS

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