MND theraputics

Question 1

what are the three principles of treatment for MND

Answer 1

neuro-protective therapy

MDT approach to supportive care

Symptoms management

Question 2

whate the different types of neuroprotective agents for MNS?

Answer 2

anti-glutamate agents: riluzole, gabapentin, lamotragine, topiramate

anti-oxidants:N-acetyl cysteine

inhibition of astrociyte activation: ONO 2506

mitochondrial dysfunction: olesoxime

neurotrophic factors: CNTF IGF-1

antiapoptotic: TCH-346 (novartis)
others: copaxonem creatine, minocycline

Question 3

what future therapies could be useful in MND?

Answer 3

Drug screening using cellular and animal models

disease biomarkers-identify subtypes, outcome

gene therapy using viral vectors

stem cells

(upcoming/ongoing trials: Tirasemtiv-fast skeletal tropin activator (phase 11), monoclonal antibody to Nogo-A: myelin associated neurite outgrowth inhibitor (phase 1)

Question 4

what symptoms can be managed using symptomatic management?

Answer 4

most common: spasticity, respiratory failure, end of life

nutrition

constipation

pain

head drop

mood disturbances and emotional lability

insomnia

respiratory and oral secretions

cramps

constipation

mobility

Question 5

describe early vs late nutritional management in MND

Answer 5

early: advice from speech therapist/dietitian

attention to food consistency/environment

nutritional supplements

late: consider intervention to bypass or supplement oral nutrition ie PEG

Question 6

what is a PEG feeding tube?

Answer 6

insert answer

Question 7

what are the benefits of gastronomy in MND?

Answer 7

adequeate nutritional intake

weight stabilisation

alternative route for medication

discharge from hospital

possible:

improved quality of life

improved survival

Question 8

what is a RIG?

Answer 8

describe

Question 9

what is a PIG?

Answer 9

hybrid technique between PIG and RIG

combines advantages of robust tube of PEG with minimal invasiveness and navigation offered by RIG

Question 10

what are the advantages of the PIG?

Answer 10

NIV

positioning

advances disease

robust tube

(maybe expand on these)

Question 11

what do we not know about gastronomy feeding?

Answer 11

when in the disease course to administer

which technique

how measure benefit?

PROGAS trial (prospective evaluation of Gastronomy in MND: 18 MND care centres)

Question 12

respiratory failure in MND can cause what?

Answer 12

sleep disturbances

daytime somnolence

headache

orthopnea

breathlessness

Question 13

what percentage of patients doe not tolerate NIV

Answer 13

20%

Question 14

what are the implications of a weak cough in MND?

Answer 14

decreased ability to mobilise and remove secretions from the airway

mucous plugs and collapsed lung

increased risk of aspiration

loss of protective mechanisms against respiratory tract infections

Question 15

compare/contrast the benefits of chest physiotherapy and cough assist

Answer 15

chest physio:
personell
time consuming
exhausting
breath stacking

cough assist:
quick
easy to use
at home
possibly effective

Question 16

what is a diaphragmatic pacing and how does it work?

Answer 16

a device inserted to regulate diagphagm and reduce breathing difficulties

transmitter sends signal via antenna to a receiver connected to the phrenic nerves which innervate the diapragm

Question 17

what mechanism of action does diapragm pacing have?

Answer 17

restore coordinated breathing

stronger contraction

conditioning

Question 18

evidence from the synapse studies for MND pacing suggests what?

Answer 18

probably safe

efficacy unproven but warrants further study

important to prevent creep (what does this mean?)

Question 19

the DIPALS trial

Answer 19

RCT comparing diaphragm pacing plus standard care (NIV) to NIV alone

108 patients in 7 centres
including sheffield