Motor Neurone Disease

Question 1

What is MND?

Answer 1

Untreatable and rapidly progressive neurodegenerative condition

Question 2

Presentation of MND?

Answer 2

Muscle weakness and wasting, secondary to motor neurone degeneration

Speech, swallowing and breathing issues may also occur

With cognitive onset MND, there are signs of cognitive impairment (causing a frontotemporal dementia)

Weight loss, mainly due to muscle wasting and/or swallowing difficulty

Question 3

Main signs of MND?

Answer 3

UMN AND/OR LMN signs WITHOUT sensory problems

Question 4

Progression of MND?

Answer 4

Focal onset but there is continuous spread, eventually resulting in generalised paresis

NOTE - MND tends to have spread of pathology in a uniform manner, e.g: if symptoms begin in right foot, they will spread up the leg rather than jumping to different regions of the body

Question 5

Types of MND?

Answer 5

MND is an umbrella term

Amyotrophic lateral sclerosis (ALS) is the most common sub-type of MND (AKA as Lou Gehrig disease)

Question 6

Clinical phenotypes of MND, with regards to LMN vs UMN involvement?

Answer 6

• PLS (primary lateral sclerosis) is rare
• UMN predominant ALS
• ‘Typical’ ALS
• LMN predominant ALS
• PMA (progressive muscular atrophy) is rare

Motor vs

Question 7

Most common MND phenotype?

Answer 7

Most common is ALS

Additional variable clinical phenotypes:
• Progressive Muscular Atrophy (PMA)
• Primary Lateral Sclerosis (PLS)
• Progressive Bulbar Palsy (PBP)

Question 8

Clinical phenotypes of MND, with regards to motor vs extra-motor symptom?

Answer 8

ALS

ALS-FTD

FTD-MND

FTD

Question 9

Clinical phenotypes of MND, with regards to regions of onset?

Answer 9

Spinal / limb onset is the most common (65%)

Bulbar onset (25%), affecting muscles responsible for speech and swallowing

Congnitive onset

Respiratory onset

Question 10

Genetics of MND?

Answer 10

Familial ALS VS sporadic ALS

High penetrance monogenic mutations include C9orf72, SOD1, TARDBP and FUS

Question 11

Most common monogenic mutation inv. with MND?

Answer 11

Intronic hexanucleotide repeat expansion C9ORF72

Question 12

Prognosis of MND?

Answer 12

Average survival is 3 years

Question 13

Occurrence of MND?

Answer 13

Rare; prevalence is low, as patients have poor prognosis

Males and females are both affected but it is slightly more common in males

Only 10% of cases are familial; 90% are sporadic

Sporadic MND peaks at 50-75 years and the risk declines >80 years; however, it can be diagnosed in younger patients

ALS less common in non-Caucasians

Question 14

UMN signs in MND?

Answer 14

Spasticity (increased tone in UMN lesions) and spastic gait

Moderate weakness

Hyperreflexia

Babinski sign is present (extensor plantar responses)

Exaggerated jaw-jerk reflex

+ve Hoffman reflex (tap the nail or flick the terminal phalanx of the middle finger; +ve response when any finger involuntarily flexes)

Slowed movements

Question 15

LMN signs in MND?

Answer 15

Muscle wasting and severe weakness

Hypotonicity

Fasciculations

Hyporeflexia or areflexia

Question 16

Presence of UMN and LMN features in the different types of MND?

Answer 16

ALS - has both UMN and LMN features
NOTE - this is also the case in ALS-FTD

PLS - UMN features only

PMA - LMN features and subclinical UMN features

Question 17

What is split hand syndrome?

Answer 17

Preferential wasting of thenar muscle group is a typical pattern of atrophy seen in ALS

There is relative preservation of abductor digiti minimi on the other side of the hand

Question 18

El Escorial diagnostic criteria for clinically definite ALS?

Answer 18

UMN and LMN signs in bulbar and at least 2 spinal regions (lumbosacral, thoracic or cervical)

OR

UMN and LMN signs in 2 spinal regions

Question 19

El Escorial diagnostic criteria for clinically probable ALS?

Answer 19

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

Question 20

El Escorial diagnostic criteria for clinically probable ALS if there is lab evidence?

Answer 20

Clinical evidence of UMN and LMN signs in 1 body region

OR

UMN signs in 1 regions and EMG findings of LMN inv. in at least 2 body regions

Question 21

El Escorial diagnostic criteria for clinically possible ALS?

Answer 21

UMN and LMN signs in only the bulbar or only 1 spinal regions

OR

UMN signs in 2 or more regions

OR

LMN signs rostral to the UMN signs

Question 22

Regions of MND?

Answer 22

1, Bulbar

2. Cervical
3. Thoracic
4. Lumbosacral

Question 23

Occurrence of primary bulbar onset MND?

Answer 23

Occurs in 25% of patient

It is more common in women and between the ages of 60-80 years

Question 24

Therapeutic interventions for primary bulbar onset MND?

Answer 24

Early communicator (speech is affected early)

Nutritional support (swallowing capability affected)

Care for URT

Question 25

Symptoms of thoracic variant of MND?

Answer 25

Dyspnoea (can occur at rest) Pneumonia

Question 26

Therapeutic interventions for thoracic variant MND?

Answer 26

Early, non-invasive intubation However, there is an increased risk of reflux, aspiration and pneumoniae

Question 27

MND, ALS variants and misdiagnoses assoc. with, in most patients, a more benign prognosis and better prognosis?

Answer 27

Flail arm syndrome - atypical presentation of ALS, characterized by upper limb weakness; no inv, of the lower limb, bulbar, or respiratory muscles Flail leg syndrome Primary lateral sclerosis (PLS) - a type of MND that only affects the UMNs; has a better prognosis than ALS Focal distal spinal muscular dystrophy Kennedy's disease - X-linked, progressive NM disease affecting spinal and bulbar neurones; it is a variant of spinal muscular atrophy and is often misdiagnosed as ALS

Question 28

Features of Kennedy's disease?

Answer 28

Gynaecomastia

Question 29

Signs of FTD?

Answer 29

Disinhibition and decreased impulse control Socially inadequate Positive mood Lack of insight

Question 30

Diagnosis of MND?

Answer 30

Clinical diagnosis - UMN and/or LMN signs with an absence of sensory symptoms Decide a phenotype, depending on site of onset and regions inv, e.g: limb onset, bulbar onset, cognitive onset Ix - EMG, neuroimaging, lab studies (CK, etc) NOTE - diagnosis of exclusion

Question 31

Common false positive conditions (MND mimic)?

Answer 31

Kennedy's disease Myopathy, e.g: inclusion body myopathy

Question 32

Conditions that MND is often misdiagnosed?

Answer 32

Carpal tunnel syndrome Stroke Neuropathy