Motor Neurone Disease

Front 1

What is motor neurone disease?

Back 1

A dysfunction of motor neurones in the brain and spinal cord causing loss of control over motor function.

Front 2

What are the types of MND?

Back 2

• ALS
  
• Primary lateral sclerosis
• Progressive muscular atrophy
• Progressive bulbar palsy

Front 3

What are the signs of upper motor neurone disease?

Back 3

• Weakness
  
• Increased muscle tone
  
• Hyper-reflexia (sensitive reflexes)
  
• Hoffman's sign (finger reflex)
  
• Babinski's sign (Foot reflex - Toes curling towards body rather than away - sign of corticospinal damage)
  
• Pronator drift - Eyes closed with arms outstretched facing upwards, palms will begin to face downwards due to impaired proprioception and patients rely on visual cues.
  

Front 4

What are the signs of lower motor neurone disease?

Back 4

• Weakness
  
• Muscle wasting
  
• Hypo-reflexia (no response to reflexes)
  
• Fasciculations (twitching)
  
• Reduced muscle tone (atrophy)
  

Front 5

What are the bulbar (facial) signs of motor neurone disease?

Back 5

• Dysphagia (difficulty swallowing)
  
• Difficulty chewing
  
• Slurred speech
  
• Difficulty handling secretions (drooling)
  
• Dysphonia (difficulty speaking)
  
• Dysarthria (Donald duck/nasal speech)
  

Front 6

What is respiratory acidosis?

Back 6

High PC02 (carbon dioxide pressure) - above 6.2 - blood gas levels mean you are unable to expel c02 effectively causing a buildup.

Front 7

Why are gastrointestinal complications common with MND patients and how are they treated?

Back 7

• Weakness in mouth/tongue/jaw causing inability to chew effectively.
  

• A gastronomy (tube inserted directly into stomach) can be used.
  

Front 8

What are the cognitive complications involved with MND and how many are affected?

Back 8

• Executive functions, language and social cognition.
  

• 35%
  

Front 9

How many develop frontoparietal dementia (FTD)?

Back 9

15%

Front 10

What is the priori hypothesis? (Ravitz)

Back 10

A set of symptoms that work in a biologically continuous order.

Front 11

What causes MND?

Back 11

Motor neurone cells shrinking and dying.

Front 12

Familial MND is due to what mutation in what gene?

Back 12

SOD1

Front 13

Why is SOD1 important?

Back 13

It is needed to rid the body of toxic free radicals (an uncharged molecule that is highly reactive) and has been found to be useful in ROS (reactive oxygen species)

Front 14

What is oxidative stress?

Back 14

ROS is helpful for oxygen metabolism however when levels get too high they kill other cells.

Front 15

What is TDP-43 protein responsible for?

Back 15

The symptoms associated with MND and repression of the HIV-1 gene.

Front 16

What does TDP-43 do?

Back 16

• Develops misfolded proteins in upper motor neurones of motor cortex (ie. folding clothes that shouldn't be folded)
  

• Protein aggregates cause harmful effects such as impairment of cell transport processes, impaired function, misfolding other proteins and removing ones that are needed for healthy motor neurone function.
  

Front 17

What does C9oRF72 protein cause?

Back 17

• Younger onset age - 57
  
• A more aggressive form of MND - 30 month life expectancy
  

Front 18

How does the C9oRF72 protein mutation cause AD?

Back 18

GGGGCC - There are typically 30 repeats in a normal person but over hundreds in AD.

Front 19

Where is C9oRF72 found?

Back 19

Neuron cytoplasm and presynaptic terminals

Front 20

What are the 2 treatment directions for AD?

Back 20

Neuroprotective and symptom management

Front 21

What are the neuroprotective treatments used for AD?

Back 21

• Anti-glutamate agents
  
• Neurotropic factors
  
• Creatine
  
• Xaliproden
  

Front 22

What anti-glutamate agents are used for treating AD and how do they work?

Back 22

• Riluzole
  
• Gabapentine
  
• Lamotrigine
  
• Topiramate
  

• They reduce glutamate as too much can harm motor neurones and inhibit signalling
  

Front 23

What are neurotropic factors and which used for treating AD?

Back 23

• Proteins that are responsible for growth and survival of developing neurons and maintenance of mature ones
  

• CNTF
  
• IGF-1
  
• BDNF
  
• GDNF
  

Front 24

What supplements are used for treating AD?

Back 24

Creatine - Encourages muscle strength/growth and reduces damage

Front 25

What does Xaliproden do?

Back 25

Encourages production of neurotropic factors such as CNTF, BNDF, GNDF.

Front 26

What are the symptomatic treatments for MND?

Back 26

• Respiratory failure - Non invasive ventilation, very effective.
  

• Weak cough - Cough assist (quick, easy to use, can use at home, more effective than chest physiotherapy)
  

• Gastronomy - Feeding tube directly inserted into the stomach, can help maintain/gain weight.