Motor Neurone Disease

Question 1

What symptoms is bulbar onset associated with?

Answer 1

• Loss of voice

* Swallowing problems

Question 2

What symptoms do people with cognitive onset present with?

Answer 2

Fronto-temporal Dementia – aggressive, disinhibited

Question 3

Name 4 high penetrance mutations in MND.

Answer 3

• C9orf72
• SOD1
• TARDBP
• FUS

Question 4

What is MND?

Answer 4

An untreatable and rapidly progressive neurodegenerative condition

Question 5

What type of diagnosis is MND?

Answer 5

Mostly clinical

Question 6

What does MND present with?

Answer 6

Muscle weakness and wasting (secondary to motor neuron degeneration)

Potentially problems with speech, swallowing and breathing problems

Question 7

To be MND, there must be what?

Answer 7

Upper +/- lower motor neurone signs, WITHOUT sensory problems

Question 8

What is the onset and progression of MND like?

Answer 8

Focal onset, and continuous spread, then finally generalized paresis

Question 9

MND exhibits various clinical __________?

Answer 9

PHENOTYPES

Question 10

What is the most common type of MND?

Answer 10

Amyotrophic Lateral Sclerosis (ALS)

Question 11

COGNITIVE IMPAIRMENT is a feature of MND.

Answer 11

TRUE

Question 12

What is the average survival time with MND?

Answer 12

3 years

Question 13

What is the lifetime risk of developing MND?

Answer 13

1 in 400

Question 14

Is MND more common in males or females?

Answer 14

Males

Question 15

What % of MND is sporadic?

Answer 15

90%

Question 16

What % of MND is familial?

Answer 16

10%

Question 17

What is the relationship between sporadic MND and age?

Answer 17

Sporadic MND peaks at the ages of 50-75 years, and declines after the age of 80

Question 18

In what population is ALS less common in?

Answer 18

Non- Caucasian

Question 19

Outline the UMN signs of MND.

Answer 19

• Increased tone
• Hyper-reflexia
• Extensor plantar responses
• Spastic gait
• Exaggerate jaw-jerk
• Slow movements

Question 20

Outline the LMN signs of MND.

Answer 20

• Muscle wasting
• Fasciculations
• Weakness
• Absent or reduced reflexes

Question 21

What % of cases of MND onset in the i) extremities ii) bulbar region iii) thoracic region?

Answer 21

i) 70%.
ii) 25%.
iii) 2%.

Question 22

Of MND that begins in the extremities, is this more likely to be in the upper or lower extremities?

Answer 22

UPPER

Question 23

At onset, what % of cases are associated with i) UMN ii) LMN iii) frontal/cognitive deficits?

Answer 23

i) 10%.
ii) 90%.
iii) 5%.

Question 24

What is the most common MND phenotype?

Answer 24

ALS

Question 25

Does ALS have UMN or LMN symptoms?

Answer 25

BOTH

Question 26

Does primary lateral sclerosis have UMN or LWM symptoms?

Answer 26

UMN

Question 27

Does progressive muscular atrophy have UMN or LMN symptoms?

Answer 27

LMN + subclinical UMN in 30%

Question 28

Does ALS- frontotemporal dementia have LMN or UMN signs?

Answer 28

BOTH

Question 29

Primary lateral sclerosis has a _____ prognosis

Answer 29

GOOD

Question 30

There is a link between ALS and what type of dementia? What is this underpinned by?

Answer 30

Frontotemporal Dementia (FTD) Underpinned by discovery of C9ORF hexanucleotide repeat expansions

Question 31

What is 'split hand syndrome' in MND?

Answer 31

Preferential wasting of the thenar group  a typical pattern of atrophy seen in ALS

Question 32

What features must be present for a diagnosis of clinically definite ALS to be made?

Answer 32

* UMN and LMN signs in bulbar AND at least two spinal (lumbosacral, thoracic or cervical) regions or * UMN and LMN signs in three spinal regions

Question 33

What features should be present for a diagnosis of clinically probable ALS to be made?

Answer 33

* UMN and LMN signs in at least 2 regions (bulbar or spinal), with some UMN signs rostral to the LMN signs

Question 34

What are the features of clinically probably ALS (lab supported)?

Answer 34

* Clinical evidence of upper and lower motor neurone signs in one body region. or * Of UMN signs in one region AND *EMG findings of LMN involvement in at least two body regions

Question 35

What are the features of clinically possible ALS?

Answer 35

``` * UMN and LMN signs in only the bulbar or only one spinal region. or * UMN signs in two or more regions. or * LMN signs rostral to UMN signs ```

Question 36

In what % of patients is there primary bulbar onset?

Answer 36

25%

Question 37

Who tends to be affected by primary bulbar MND?

Answer 37

Women > men | 60-80 years old

Question 38

What always results from primary bulbar MND?

Answer 38

Generalisation into ALS

Question 39

Suggest therapeutic interventions for primary bulbar MND.

Answer 39

Early communicator. Nutritional support. Care for URT.

Question 40

A diagnosis of MND is a diagnosis of _________

Answer 40

EXCLUSION

Question 41

What is the broad phenotype of MND due to?

Answer 41

* Site of onset | * Regions involved

Question 42

What is the consensus clinical criteria for MND?

Answer 42

UMN signs +/- LMN signs WITHOUT any sensory symptoms

Question 43

What are the potential types of MND?

Answer 43

* Classic MND (or Amyotrophic lateral sclerosis ALS) * Progressive Muscular Atrophy (PMA) * Primary Lateral Sclerosis (PML) * Syndromes of MND and frontotemporal dementia (FTD-MND) * Progressive Bulbar Palsy * Flail Limb

Question 44

State 3 frequent misdiagnosis of MND?

Answer 44

Carpal tunnel syndrome. Stroke. Neuropathy.

Question 45

What UMN signs are associated with MND? (make sure to mention bulbar, cervical and lumbar region and abdominal region signs)

Answer 45

* Spasticity * Babinski sign * Bulbar UMN Signs: Exaggerated snout reflex. Clonic Jaw Jerk. Emotional Lability. Forced Jaw Opening * Cervical and Lumbar Region: Clonic Deep Tendon Reflexes. Preserved Reflex in a Weak, Wasted Limb. Hoffmann Reflex. Hyper-reflexia * Abdominal Region: Loss of superficial abdominal reflexes

Question 46

What medication is used in MND?

Answer 46

Riluzole

Question 47

How are communication needs met in MND?

Answer 47

Speech therapy | * Technology from tablets to ‘voice banking’)

Question 48

How are nutritional needs met in MND?

Answer 48

* Gastrostomy | * Dietetics

Question 49

How are resp needs met in MND?

Answer 49

* Assessment | * Home ventilation

Question 50

What have been identified as the pathological signature in 95% of cases?

Answer 50

TDP43 inclusions

Question 51

Of the newly discovered causative monogenetic mutations, what is the most common?

Answer 51

The intronic hexanucleotide repeat expansion C9ORF72

Question 52

What does C9ORF72 account for?

Answer 52

10% of the sporadic cases, and is very common in familial forms

Question 53

What % of MND cases are now classified as monogenetic?

Answer 53

10-15%