6a. Multiple Sclerosis

Question 1

Name 4 facts about MS.

Answer 1

1. It is the leading cause of non-traumatic neurological disability in young adults.
2. It is an autoimmune disease.
3. Most cases occur between the ages of 20-40.
4. It is more common in woman (3:1) and more common in countries further from the equator.

Question 2

What are risk factors of MS?

• Genetic factors
• Environmental factors (3x)

Answer 2

Genetic factors: the incidence in first degree relatives is 20 times higher than in the general population. The concordance rate is 30% in mono-zygotic twins, so environmental effects are also involved.

Environmental factors:

1. Low vitamin D
2. Epstein-Bar Virus
3. Smoking

Question 3

What are the most common symptoms of MS in early stages? (8x)

Answer 3

1. Double/blurred vision
2. Numbness
3. Weakness in extremities
4. Instability in walking
5. Tremors
6. Problems with bladder control
7. Cognitive problems
8. Mood problems (depression/anxiety)

Question 4

Course

What 2 phases of MS can you distinguish?

Answer 4

1. Relapsing-remitting phase

2. Secondary progressive phase

Question 5

Explain the relapsing-remitting phase of MS.

Answer 5

Early stage of the disease > autoreactive immune celss traffic into the CNS > results in focal inflammation and demyelination (visible as gadolinium-enhancing lesions on MRI) > relapses are then followed by periods of remission as inflammation resolves and remyelination occurs.

Question 6

Explain the secondary progressive phase of MS.

Answer 6

Over time chronic inflammation with scar formation (=sclerosis), accumulation of axonal damage, brain atrophy, and inhibition of remyelination contribute to progressive worsening.

Question 7

Name 5 types of lesions in MS.

Answer 7

1. Juxtacortical lesion
2. Periventricular lesion
3. Lesion in the pons
4. Lesion in the spinal cord
5. Gadolinium-enhancing lesion

Question 8

Explain a juxtacortical lesion?

Answer 8

Lesion in or near the cortex

Question 9

Explain a periventricular lesion

Answer 9

Lesion between cortex and ventricles

Question 10

Explain a lesion in the pons

Answer 10

Lesion in part of the brain stem (=pons)

Question 11

Explain lesion in the spinal cord

Answer 11

Lesion in C5, C6

Question 12

Explain a gadolinium-enhancing lesion

Answer 12

Lesion caused by active inflammation

Question 13

McDonald 2017 diagnosis MS (based on neurological exam)

Name 2 statements.

Answer 13

1. Dissemination in space = 1 or 2 lesions typical of MS present in 2 or more sites within the CNS.
2. Dissemination in time = requires that 2 attacks seperated by more than 30 days have occured in different parts of the CNS.

Question 14

Tests to confirm the diagnosis of MS

Why MRI?

Answer 14

To look for signs of inflammation (T2-hyperintense & gadolinium-enhanced lesions)

Question 15

Tests to confirm the diagnosis of MS

Why blood test?

Answer 15

To exclude other conditions (vitamin deficiency, lupus erythematosus)

Question 16

Tests to confirm the diagnosis of MS

Why spinal tap?

Answer 16

To extract CSF to analyze the number of white blood cells (reflect immune system functioning), neurofilaments (reflects axonal damage due to inflammation), or oligoclonal bands (reflects inflammatory activity in the CNS).

Question 17

Tests to confirm the diagnosis of MS

Why evoked potential tests?

Answer 17

To examen how long it takes for the brain to respond to visual stimulation, since MS often starts with visual problems due to damage to the optic nerves (looking at a flashing chessboard pattern with electrodes).

Question 18

Which 6 neuropsychiatric problems are very common in MS?

Answer 18

1. Major Depression
2. Bipolar Affective Disorder
3. Euphoria
4. Psychosis
5. Personality change
6. Anxiety disorders

Question 19

Neuropsychiatric problems in MS

Explain depression

• Why depression in MS?
• Causes (3x)

Answer 19

Many symptoms overlap, such as fatigue, sleep, appetite disturbances, and abnormalities in concentration.

Causes of depression in MS:

1. T2 lesions in the prefrontal cortex and temporal lobe
2. Less gray matter and greater CSF volume in the temporal lobe.
3. Reactive: uncertainty, hope, helplessness, inadequate coping strategies, fatigue.

Question 20

Neuropsychiatric problems in MS

Explain bipolar disorder

• Prevalention
• Tried of symptoms
• Treatment

Answer 20

Twice as prevalent as in the general population.

Tried of symptoms:

1. Elevated or irritable mood
2. Grandiose or persecutory thinking
3. Increased psychomotor activity

Treatment: mood stabilizing medication & sedation

Question 21

Neuropsychiatric problems in MS

Explain euphoria

Answer 21

A defixed state of well-being despite the presence of considereable physical morbidity (lack of insight)

Question 22

Neuropsychiatric problems in MS

Explain psychosis

Answer 22

2-3 times more common and associated with a higher lesion load in medial temporal lobe regions.

Treatment: anti-psychotic medication

Question 23

Neuropsychiatric problems in MS

Name 2 causes of personality changes in MS.

Answer 23

1. Damage in orbitofrontal-subcortical circuits = profane, disinhibited and socially inappropriate behaviors.
2. Damage in anterior cingulate-subcortical pathways = apathy & indifference

Question 24

What are the 2 most commonly affected domains in MS?

Which area is mostly associated with cognitive impairments in MS?

Answer 24

1. (Visual) memory
2. Information processing speed (=hallmark in MS)

Area: especially thalamic atrophy

It does not correlate with disease duration, only, not al MS patients experience it.

Question 25

On which 3 areas do cognitive problems affect the quality of life in MS patients?

Answer 25

1. Participation: employment, social function, daily activities, physical indepencence 2. Relationships: caregivers experience high levels of distress due to the patient's cognitive problems, and less their physical symptoms 3. Safety: falls, driving > information processing speed, spatial learning, and recall are important predictors for driving performance and accidents

Question 26

Assessment of cognition in MS Which 4 types of assessments can you distinguish?

Answer 26

1. Screening tests (routine in the office) 2. Brief batteries (routine in neuropsychological exam) 3. Intermediate length batteries 4. Comprehensive ad-hoc batteries (for differential diagnoses, work disability questions, and rehabilitation programs)

Question 27

Which 2 screening tests for cogntion in MS can you distinguish?

Answer 27

1. Symbol Digit Modalities Test (SDMT) | 2. MS Neuropsychological Screening Questionnaire

Question 28

Explain the SDMT in MS.

Answer 28

Symbol Digit Modalities Test = the most popular test in MS. Used as a minimum baseline screening and repeated yearly (5 min duration). It examines information processing speed and working memory (substitute meaningless symbols by corresponding numbers)

Question 29

Explain the MS Neuropsychological Screening Questionnaire.

Answer 29

Needs to be filled in by the patient and informant. Self-reported scores correlate more with depression, informant-reported scores more with cognitive dysfunction.

Question 30

What is the BRNB in MS?

Answer 30

Brief Neuropsychological Battery

Question 31

Which 5 tests are included in the Brief Neuropsychological Battery in MS?

Answer 31

1. Symbol Digit Modalities Test (SDMT) 2. Selective Reminding Test 3. 10/36 Spatial Recall Test (SPART) 4. Paced Auditary Serial Addition Test (PASAT) 5. Word list generation

Question 32

Brief Neuropsychological Battery in MS Explain the Selective Reminding Test

Answer 32

To measure verbal learning and memory recall. It's similar to the 15WT, but here are 12 words and only the words that are missed are given by the test instructor.

Question 33

Brief Neuropsychological Battery in MS Explain the 10/36 Spatial Recall Test (SPART)

Answer 33

To assess visuospatial learning and late recall. It's a board with dots that the subject has to reproduce.

Question 34

Brief Neuropsychological Battery in MS Explain the Paced Auditary Serial Addition Test (PASAT)

Answer 34

2nd most popular test in MS. To assess processing speed and working memory. Patients need to add pairs of digits presented at 2 rates of speed. The 2 second condition is hard for MS patients.

Question 35

Brief Neuropsychological Battery in MS Explain the Word list generation test

Answer 35

A semantic fluency test (vegetables, fruits, animals)

Question 36

Which 3 treatment options for MS can you distinguish? And explain.

Answer 36

1. Disease modifying therapies: it might help to preserve intact cognitive functioning and delay the development of cognitive impairment, however, weak positive effects on cognition. 2. Acetylcholinesterase inhibitors: promising, but studies with small sample size. 3. Behavioral interventions: cognitive/strategy training (limited data on effectiveness, but targeted interventions to improve acquisition in verbal memory and learning show promise)