MND Management

Question 1

The 2017 study of the King’s MND Centre found that the multidisciplinary team approach improved what?

Answer 1

Survival by 20%, independently of other treatment

Question 2

What happens in the initial appointment for MND management?

Answer 2

▪️Meet consultant at Motor Nerve Clinic for 1.5 hours
▪️History of symptoms and review tests to give diagnosis if possible
▪️Preliminary advice and point of contact
▪️Info on research and genetic testing
▪️Offered follow up in 2-4 weeks

Question 3

Who do patients see at their follow-up?

Answer 3

▪️Clinical Nurse Specialist
▪️Palliative care consultant
▪️Research/Trials team
▪️Other specialists such as PT, OT, SLT, wheelchair specialist, voice banking specialist etc

Question 4

How often to patients meet with neurologists and the team for a review?

Answer 4

Every 3-6 months

Question 5

What is the only disease modifying drug available in the UK?

Answer 5

Riluzole

Question 6

How is riluzole thought to work?

Answer 6

Through glutamate action, potentially reducing the excitability of neurons, although exact mechanisms are unclear

Question 7

What is the main clinical effect of riluzole?

Answer 7

5-year survival improves from 13 to 37% (modest effect on progression)

Is this clinically relevant enough?

Question 8

What are the key considerations when prescribing riluzole?

Answer 8

It is relatively safe but increases risk of pulmonary fibrosis, so regular blood tests are needed every year to check FBC, LFTs and electrolytes

Question 9

What other disease modifying drugs are available in other countries?

Answer 9

Edaravone (given via IV) - modest effect on progression but only available in US and Japan

Question 10

What support can be be given for those with breathing difficulties?

Answer 10

Non-invasive ventilation - mask pushes air into the body if the diaphragm can’t contract

Particularly useful over night

Question 11

What support can be given to help manage swallowing difficulties?

Answer 11

▪️PEG - percutaneous endoscopic gastronomy
▪️RIG - radiologiclly inserted gastronomy

Question 12

What is the main limitation of non-invasive ventilation?

Answer 12

Reasonable ventilatory reserve is needed to get it fitted so it is best this is done before they need it and they are too weak

Question 13

What is the main benefit of palliative care?

Answer 13

Improved quality of life

Question 14

What MND symptoms can be managed with symptom modifying medication?

Answer 14

▪️Emotional lability
▪️Cramps
▪️Spasticity
▪️Sialorrhoea

Question 15

What is sialorrhoea?

Answer 15

Increase of saliva due to weakness in the swallowing muscles

Question 16

What are the main treatments for emotional lability in MND?

Answer 16

▪️Antidepressants, such as citalopram
▪️Neudexta (only in US)

Question 17

Who is at most risk of swallowing and breathing difficulties?

Answer 17

Those with bulbar involvement

Question 18

What is the main treatment for cramps in MND, particularly in the legs at night?

Answer 18

Quinine sulphate

BUT questions over safety

Question 19

What medications can be used to help spasticity in MND?

Answer 19

▪️Baclofen
▪️Tizanidine
▪️Dantrolene
▪️Gabapentin

Question 20

What medications can be used to manage sialorrhoea in MND?

Answer 20

▪️Hyoscine patches
▪️Atropine drops
▪️Glycopyronium
▪️Amitriptyline
▪️Botox
▪️Radiotherapy (last resort)

Question 21

What is anarthria?

Answer 21

Total inability to articulate speech despite intact auditory comprehension and written language

Question 22

What is bulbar onset MND?

Answer 22

A subtype of MND (~20%) that primarily affects the muscles of the face, throat, and tongue

May initially present with slurring speech or dysphagia

Aka progressive bulbar palsy (PBP)

Question 23

Where would you target botox or radiotherapy for treatment of sialorrhoea?

Answer 23

The parotid glands (largest salivary glands)

Question 24

What is the MIROCALS study and what have they found?

Answer 24

▪️Phase 2 research at King’s repurposing a renal cancer drug
▪️Control neuroinflammation
▪️Significant improvement in survival of a subset of patients
▪️Not so beneficial for very mild and severe patients?

Question 25

What is the VALOR trial and what did they find?

Answer 25

▪️Phase III trial of tofersen
▪️Reduced SOD1 concentrations in CSF
▪️No significant effect on functioning or clinical end point
▪️7% developed serious neurological AE

Question 26

What is Tofersen?

Answer 26

An anti-sense oligonucleotide that reduces synthesis of SOD1 protein

Question 27

What is the ATLAS trial?

Answer 27

A trial currently recruiting participants to study tofersen in presymptomatic individuals with confirmed SOD1 mutation

Question 28

What are the current challenges to MND research?

Answer 28

▪️Strict eligibility criteria
▪️Need for better understanding of pathogenesis
▪️Increasing access and open label extensions
▪️Less placebo
▪️Funding
▪️Staffing
▪️Need patient input

Question 29

What is Reldesemtiv?

Answer 29

A fast skeletal muscle troponin activator that increases interaction between proteins, allowing muscles to tighten and increasing muscle strength

Aim to improve QoL, not modify disease.

Question 30

What is the FORTITUDE-ALS trial and what did they find?

Answer 30

A trial of Reldesemtiv which found reduced decline compared to placebo

It’s follow up study is COURAGE

Question 31

What other mutations have been explored as targets for disease modifying treatment of MND?

Answer 31

▪️C9orf72 (Focus C9 trial) - discontinued due to lack of effect
▪️FUS (Fushion trial) - currently recruiting

Question 32

What is the Lighthouse Project?

Answer 32

An ongoing trial testing an antiretroviral drug repurposed from HIV (Triumeq).

Shows promise for increasing survival but can cause allergies

Question 33

What is KCL MND Biobank?

Answer 33

A central resource of samples and information from patients with MND and healthy controls

Question 34

What is the MND SMART study?

Answer 34

Upcoming multi-arm, multi-stage RCT investigating memantine (dementia drug) and trazodone (antidepressant)