MND Management Flashcards
The 2017 study of the King’s MND Centre found that the multidisciplinary team approach improved what?
Survival by 20%, independently of other treatment
What happens in the initial appointment for MND management?
▪️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
Who do patients see at their follow-up?
▪️Clinical Nurse Specialist
▪️Palliative care consultant
▪️Research/Trials team
▪️Other specialists such as PT, OT, SLT, wheelchair specialist, voice banking specialist etc
How often to patients meet with neurologists and the team for a review?
Every 3-6 months
What is the only disease modifying drug available in the UK?
Riluzole
How is riluzole thought to work?
Through glutamate action, potentially reducing the excitability of neurons, although exact mechanisms are unclear
What is the main clinical effect of riluzole?
5-year survival improves from 13 to 37% (modest effect on progression)
Is this clinically relevant enough?
What are the key considerations when prescribing riluzole?
It is relatively safe but increases risk of pulmonary fibrosis, so regular blood tests are needed every year to check FBC, LFTs and electrolytes
What other disease modifying drugs are available in other countries?
Edaravone (given via IV) - modest effect on progression but only available in US and Japan
What support can be be given for those with breathing difficulties?
Non-invasive ventilation - mask pushes air into the body if the diaphragm can’t contract
Particularly useful over night
What support can be given to help manage swallowing difficulties?
▪️PEG - percutaneous endoscopic gastronomy
▪️RIG - radiologiclly inserted gastronomy
What is the main limitation of non-invasive ventilation?
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
What is the main benefit of palliative care?
Improved quality of life
What MND symptoms can be managed with symptom modifying medication?
▪️Emotional lability
▪️Cramps
▪️Spasticity
▪️Sialorrhoea
What is sialorrhoea?
Increase of saliva due to weakness in the swallowing muscles
What are the main treatments for emotional lability in MND?
▪️Antidepressants, such as citalopram
▪️Neudexta (only in US)
Who is at most risk of swallowing and breathing difficulties?
Those with bulbar involvement
What is the main treatment for cramps in MND, particularly in the legs at night?
Quinine sulphate
BUT questions over safety
What medications can be used to help spasticity in MND?
▪️Baclofen
▪️Tizanidine
▪️Dantrolene
▪️Gabapentin
What medications can be used to manage sialorrhoea in MND?
▪️Hyoscine patches
▪️Atropine drops
▪️Glycopyronium
▪️Amitriptyline
▪️Botox
▪️Radiotherapy (last resort)
What is anarthria?
Total inability to articulate speech despite intact auditory comprehension and written language
What is bulbar onset MND?
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)
Where would you target botox or radiotherapy for treatment of sialorrhoea?
The parotid glands (largest salivary glands)
What is the MIROCALS study and what have they found?
▪️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?
What is the VALOR trial and what did they find?
▪️Phase III trial of tofersen
▪️Reduced SOD1 concentrations in CSF
▪️No significant effect on functioning or clinical end point
▪️7% developed serious neurological AE
What is Tofersen?
An anti-sense oligonucleotide that reduces synthesis of SOD1 protein
What is the ATLAS trial?
A trial currently recruiting participants to study tofersen in presymptomatic individuals with confirmed SOD1 mutation
What are the current challenges to MND research?
▪️Strict eligibility criteria
▪️Need for better understanding of pathogenesis
▪️Increasing access and open label extensions
▪️Less placebo
▪️Funding
▪️Staffing
▪️Need patient input
What is Reldesemtiv?
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.
What is the FORTITUDE-ALS trial and what did they find?
A trial of Reldesemtiv which found reduced decline compared to placebo
It’s follow up study is COURAGE
What other mutations have been explored as targets for disease modifying treatment of MND?
▪️C9orf72 (Focus C9 trial) - discontinued due to lack of effect
▪️FUS (Fushion trial) - currently recruiting
What is the Lighthouse Project?
An ongoing trial testing an antiretroviral drug repurposed from HIV (Triumeq).
Shows promise for increasing survival but can cause allergies
What is KCL MND Biobank?
A central resource of samples and information from patients with MND and healthy controls
What is the MND SMART study?
Upcoming multi-arm, multi-stage RCT investigating memantine (dementia drug) and trazodone (antidepressant)
