Motoneurone disease & Myaesthenia Gravis Flashcards
What is Motor Neurone disease?
- 3rd most prevalent neurodegenerative disorder
- Group of diseases
1. Progressive degeneration of motoneurons in brain and spinal cord innervating (skeletal) voluntary muscles
2. Muscle contraction weakness
3. Loss of muscle mass
4. Inability to control movement - Affects
1. 0.4-1.8/100,000 people
2. 1.6F :1M - Age of onset
1. 40-60 - Mean survival
1. 4 years (up to 20) - Cause of death
1. Respiratory weakness
2. Pneumia
What are the overall symptoms of motor disorders in MND?
- Affects how you walk, talk, eat, drink and breathe
- In some cases, cognitive and behavioural changes
- Not all symptoms will affect everyone, or in same order
- Symp prog at varying speeds
- MND has no cure
What are the 4 major diseases in MND?
- Amyotrophic Lateral sclerosis (ALS)
- Progressive Bulbar Palsy (PBP)
- Progressive muscular atrophy (PMA)
- Primary Lateral Sclerosis (PLS)
What is ALS?
Commonest form
* Affects all motorneurons
1. Direct control of skeletal muscle tension mediated by ACh at the NMJ
- Weakness and wasting in limbs
- Muscle stiffness and cramps
- LE: 2-5 Years from onset of symptoms
Extra-ocular muscles usually spared
First affected Organs
* Tongue, hand, leg muscles
Specific Motor degeneration
* Preserved cognitive function
* Preserved Sensations
What is Progressive Bulbar Palsy (PBP)?
- Affects less people than typical ALS (10% of MND)
- Mainly affects the muscles of the face, throat and tongue
- Early symptoms: Slurring of speech or diff swallowing
- LE: 6 months to 3 years
What is progressive muscular atrophy (PMA)?
- Affects only a small proportion of people (4% of MND)
- Early symptoms: Weakness or clumsiness of the hands
- LE: More than 5 years
What Primary Lateral sclerosis (PLS)?
- Rare form of MND (1-3% of cases)
- Mainly weakness in lower limbs
- Sometimes clumsiness in the hands or speech problems
- Slow Progression, can evolve to ALS
- LE: 10-20 Yo
What is Kennedy’s disease?
- Not a type of MND, but has similar symptoms
- Rare condition affecting the moto neurones
- Inc weakness and wasting of muscles
- Unlike MND, kennedys also causes hormonal changes
- Normal LE
How do you diagnose MND?
- Clinical examination - To recognise signs
-
Blood tests
* Incd levels of creatine kinase, produced when muscle breaks down
* Enzyme found in heart, brain, skeletal muscle
* Also found in other conditions (e.g. Heart attack, muscle inury, alcohol, medicine) -
Electromyography (EMG)
* Fine needles record the natural nerve impulseswithin certain muscles
* Detect early changes, even if muscle activity still seems normal -
Nerve Conduction tests
* Electrical impulse applied thhrough a small pad skin
* This measures the speed at which nerves carry electrical skignals -
Transcranial Magnetic Stimulation (TMS)
* Measures activity of upper motor neurones -
Magnetic Resonance Imaging (MRI)
* Rule out conditions such as stroke, Alzheimer’s disease, Parkinson’s, MS, tumours and trapped nerves, and injury to spine and brain
What changes occur neurologically in MND?
- Ventral Horn Shrinks:
1. Dec choline acetyltransferase
2. Normal nerve conduction velocity
3. Decd motoneurone terminal sprouting
4. Incd glutamate levels in CSF
What are the early symptoms?
- The first noticeable symptom is weakness of the eye muscles, difficulty in swallowing and slurred speech may also be first signs
What are the Causes of ALS?
- Genetic: 5-10% of ALS cases are familial
-
Autosomal dom with age-dep penetrance - Chromosome 9 (Mut C9orf72)
—–25-40% of all familial ALS cases
—–Also in 7% of sporadic cases -
Chromosome 21: Mutations of SOD1
—-10-15% familial cases
—-1-2% sporadic ALS - Autosomal Recessive
- ALS2 gene, chromosome 2q33
- Encodes ALSIN, present in motoneuron (Long and short form , long protective, short bad)
What are the Causes of ALS? (2)
Atypical late-onset form ALS
* Mutation of vesicle-associated mem protein B gene on Chromosome 20
* Dysfucntion of intracellular memvrane traficking
Rare autosomal dom juvenile ALS
* RNA/DNA helicase controlling RNA processing
What causes Sporadic ALS?
- Gene mutation
- Chemical imbalance (Glutamate)
* High levels are toxic - Protein mishandlinf
- Disorganised immune response
- Environmental toxin exposure
* 2X increase of ALS in military due exposure to certain metals/chemicals etc
What are the potential mechansims of MN degneration?
- Activation of Glutamate receptors
- Superoxide Dismutase 1 mutation
- Mutation of neurofilament genes
