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Neuroscience 2 > Clinical Features of Multiple Sclerosis > Flashcards

Clinical Features of Multiple Sclerosis Flashcards

Understand MS epidemiology, incidence, and potential mechanisms accounting for the variability of MS incidence worldwide Describe clinical phenotypes of MS, the disease course, and presenting clinical symptoms Understand imaging features, clinical and laboratory tests, and the key diagnostic criteria, along with potential differential diagnoses Describe the variability of disease course, severity, and clinical and radiological factors affecting prognosis

1
Q

Define multiple sclerosis

A

A chronic inflammatory, multifocal, demyelinating disease of the CNS of unknown cause which results in the loss of myelin with oligodendroglial and axonal pathology

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2
Q

Describe the prevalence of MS

A

MS affects 2.5 million individuals worldwide and is more common in higher latitude countries. UK prevalence is 258 per 100,000 women and 113 per 100,000 men

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3
Q

Is MS associated with a decrease in life expectancy?

A

Yes, by 7-14 years

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4
Q

Describe the impact of MS on employment status and relationships

A

MS reduces the likelihood of individuals being in word, with just 31% in work after 15y of disease (compared to 89% of age-matched controls). After 24 years of disease, 33% of MS patients are in a relationship, compared to 53% of age-matched controls

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5
Q

What percentage of individuals with MS have cognitive impairment?

A

57%

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6
Q

In MS-associated cognitive impairment, which domains are most affected?

A

Memory, speed of information processing, attention, and executive functioning

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7
Q

Give at least 3 environmental factors implicated in the aetiology of MS

A

Latitude, sunlight exposure, vitamin D, viral infections (e.g. Epstein-Barr virus)

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8
Q

Describe how the latitude within the UK affects MS incidence and prevalence

A

Incidence and prevalence are highest in Scotland - with incidence 13 per 100,000 and prevalence 209 per 100,000 - followed by NI, then England, then Wales. Thus, incidence and prevalence mirrors the latitude of each country

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9
Q

Describe Munger et al’s 2004 and 2006 research into vitamin D and MS

A

Munger et al found that low vitamin D intake, and low 25-hydroxy-vitamin D serum level, increased the risk of MS - especially at high latitude

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10
Q

How does Kurtzke’s 1979 research go against vitamin D’s role in MS?

A

It describes how black individuals are more likely to be vitamin D deficient than white individuals, yet have a lower risk of MS

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11
Q

Describe how Dean & Kurtzke’s 1971 research suggests a period of MS susceptibility in early life

A

They found that migrants aged 15 or older moving from Northern Europe to South Africa retained a North European likelihood of developing MS, but migrants below 15 acquired the incidence of native-born South Africans

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12
Q

Describe Dobson et al’s 2013 observations on the ‘month of birth effect’ on MS susceptibility

A

The risk of developing MS is slightly higher amongst those born in May, and lower amongst those born in November. This could be due to lower exposure to the sun during pregnancy through winter, and therefore lower maternal vitamin D

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13
Q

Describe the seasonal effect on MS lesion and clinical activity

A

MS activity is higher both clinically and on MRI in the spring and summer months, which could be due to low levels of sunlight and vitamin D through winter

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14
Q

Describe Ascherio et al’s 2000 and 2007 evidence for a role of EBV in MS aetiology

A

The distribution of infectious mononucleosis - caused by EBV - and MS is the same in terms of latitude, commonality in high-income populations, and commonality in women. The risk of MS also appears to be affected by EBV sero-status, with the risk 13x greater in individuals sero-positive for EBV antibodies

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15
Q

What percentage of the world’s population is EBV sero-positive?

A

90-95%

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16
Q

Which class of genes has the strongest effect on genetic risk?

A

HLA class II

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17
Q

What is the concordance rate of MS between monozygotic twins?

A

25-30%

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18
Q

Describe the evidence for a hormonal role in MS

A

1) The incidence of MS in women has almost doubled in the past 50 years.
2) MS activity decreases during pregnancy and increases in the first 3 months post-partum.

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19
Q

Define relapses, as applied to MS

A

Acute-onset episodic neurological symptoms lasting for over 24 hours in patients otherwise free from concominant illness. After the relapse, the patient will exhibit complete or partial recovery

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20
Q

Define progression, as applied to MS

A

Insious-onset relentless and irreversible accumulation of disability for at least one year - although occasional plateaus and minor temporary improvements can be observed

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21
Q

What is the pathological substrate of relapse?

A

Demyelinated plaques in the white matter

22
Q

What causes the functional impairment in MS?

A

Demyelination delays the nerve impulse

23
Q

Give 5 common lesion locations and common symptoms of MS relapse

A

1) Optic nerve - optic neuritis (monocular vision loss)
2) Spinal cord - limb weakness and spasticity, paraesthesia; pain or sensory loss in limbs or trunk; urinary urgency and incontinence; sexual dysfunction
3) Brainstem - diplopia; pain (trigeminal neuralgia); numbness of face or tongue; nystagmus or vertigo; dysarthria
4) Cerebellum - ataxia, loss of limb coordination
5) Cerebrum - memory loss; impaired attention; hemiparesis; hemisensory loss; visual field deficit; seizure; psychiatric disturbance

24
Q

Name some objective signs on MS examination

A

Weakness, spasticity, sensory loss, impaired coordination, action or intention tremor, unilateral visual loss, conjugate eye movement disorders, ataxic and spastic gait, optic neuritis

25
Q

What percentage of MS cases are relapsing-remitting?

A

80-85%

26
Q

What is the average age of onset of relapsing-remitting MS?

A

30

27
Q

What causes conversion from relapsing-remitting MS to secondary progressive MS?

A

Initially, patients with relapsing-remitting MS have a high level of inflammation - the fluctuations in inflammatory activity cause relapses. This decreases over time, Inflammation is accompanied by axonal loss which steadily increases. Demyelination is temporary as myelin can regenerate - but eventually, remyelination fails, leaving axons unsupported with axon death. This axon death causes the progressive phase

28
Q

What is the difference in age of onset between primary and secondary progressive MS?

A

None - both have an average age of onset of 40

29
Q

Describe the 2 criteria which must be fulfilled for a diagnosis of MS

A

CNS lesions separate in time and separate in space

30
Q

Give at least 3 systemic immune diseases which can mimic MS by affecting the CNS

A

Neurosarcoidosis, systemic lupus erythematosus (SLE), anti-phospholipid syndrome, Sjogren’s syndrome, CNS vasculitis, Behcet’s syndrome

31
Q

Name 2 CNS-specific inflammatory syndromes which can mimic MS

A

Acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica (NMO)

32
Q

Define the MRI diagnostic criteria of MS

A

1) More than one T2 lesion in at least 2 or 4 typical locations for MS - periventricular, subcortical, infratentorial, spinal cord
2) Dissemination in time of lesions - a new T2 or GAD-enhancing lesion on a follow-up MRI, or simulatenous presence of GAD-enhancing and non-enhancing lesions at any time

33
Q

What does GAD enhancement imply about a lesion?

A

That is is less than 6 weeks old, causing blood-brain barrier disruption yet to be repaired

34
Q

Describe a typical MRI T2 MS lesion

A

Round or ovoid demyelinated plaque 3-10mm in size. Typical locations include the periventricular region, cerebellum, around the corpus callosum, or the brainstem

35
Q

How much more common are new MRI lesions than clinical attacks?

A

5-10x

36
Q

What will CSF analysis in MS show?

A

Increased production of immunoglobulin and the presence of oligoclonal bands which are not present in the serum

37
Q

How can electrophysiology aid an MS diagnosis?

A

Delayed visual evoked potentials indicate visual pathway dysfunction even in patients with no visual symptoms

38
Q

How is disability in MS measured?

A

With the expanded disability status scale (EDSS)

39
Q

What is the median length of time from disease onset to EDSS 6, and what is EDSS 6?

A

18 years. EDSS is when assistance becomes required for walking

40
Q

Name the condition when patients have experienced a single MS-type attack but do not fulfil the dissemination in time and space criterion

A

Clinically isolated syndrome

41
Q

Describe how MRI appearance indicates the risk of converting from clinically isolated syndrome to MS

A

A normal brain MRI indicates a 20% risk, whereas 2 or more demyelinating lesions indicate a 90% risk

42
Q

How long does it take for the average person with primary progressive MS to progress to EDSS 6?

A

10 years

43
Q

Give 5 positive prognostic indicators in MS

A

Young onset, female gender, optic neuritis or sensory symptoms only at onset, low frequency of early attacks, complete symptom remission, long first inter-attack interval

44
Q

State 5 negative prognostic indicators in MS

A

> 40 at onset, male gender, insidious pyramidal tract involvement, frequent early attacks, prominent cerebellar involvement, rapid development of fixed disability

45
Q

State 5 secondary complications of MS

A

Depression, UTI, limb contractures from spasticity, gastroparesis and intestinal pseudo-obstruction, accelerated lumbar spondylosis from abnormal posture, aspiration pneumonia, pulmonary embolism, pressure sores

46
Q

Define acute disseminated encephalomyelitis

A

An acute or subacute monophasic inflammatory and demyelinating process of the CNS following a prodromal infection, typically under the age of 10

47
Q

State some symptoms of acute disseminated encephalomyelitis

A

Motor deficits, bilateral optic neuritis, encephalopathy, seizure

48
Q

Define neuromyelitis optica

A

A severe CNS demyelinating syndrome characterised by optic neuritis and acute myelitis, which can follow an acute monophasic or relapsing course

49
Q

Who is typically affected by neuromyelitis optica?

A

Females over 35

50
Q

Describe the differences between MS and neuromyelitis optica

A

CSF: High white cell count >50 cells/mm3 (usually normal in MS, or at least below 20 cells/mm3), low frequency oligoclonal bands
MRI: Cord lesion extending at least 3 vertebral segments but normal brain MRI (both affected in MS)

Neuroscience 2 (30 decks)

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