Motor neuron disease

Question 1

what is mnd or amyotrophic lateral sclerosis (als)

Answer 1

degen/death of mn that spreads until fatal
50+ yrs
respiratory failure
death 2yrs after diagnosis
symptoms usually begin with weakness in arms/legs => trouble with fine mvm of hands

Question 2

UMN vs LMNs

Answer 2

upper mn = cell bodies in cerebral cortex that issues commands to LMNs (via corticospinal tract)
lower mns = cell bodies in spinal cord/brainstem, innervate skeletal muscle

Question 3

define amyotrophy and lateral sclerosis

Answer 3

amyotrophy = muscle wasting, LMN
lateral sclerosis = loss of lateral corticospinal tract, UMN

Question 4

different subtypes of mn

Answer 4

UMN only, LMN only, UMN + LMN
- progressive bulbar palsy
- primary lateral sclerosis
- flail arm + leg syndrome
- ALS-dementia

Question 5

What are the features of MND

Answer 5

one of most common neuromuscular diseases worldwide
2 aussies die every day, kills within 2 years
cause unknown, no cure
only current licensed treatment = riluzole = NMDA antagonist = extend life by 3 months
sensation preserved bc only effecting mn
few groups of mns spared (sphincter control, extraocular muscles)

Question 6

symptoms of mnd

Answer 6

umn/lmn loss
pathological fasciculations (ectopic discharge)
muscle weakness, cramps, flaccid paralysis
hyperreflexia, spastic paralysis (UMN)

Question 7

what symptoms do UMN disorders cause

Answer 7

spasticity = descending info slowly diminishing = muscle contractions happen spastically
overactive tendon reflexes
abnormal babinski sign

Question 8

what symptoms do LMN disorders cause

Answer 8

flaccidity
atrophy
muscle twitches
decreases muscle tone
loss of tendon reflexes

Question 9

how do you diagnose mnd

Answer 9

possible/probably diagnosis
confirmation only post-mortem
mn degeneration determined by clinical tests (babinski), electrophysiological studies (compensatory upregulation of ACh receptors by denervated muscle fibres)
rule out other diseases

Question 10

what are the different % of the different types of MND

Answer 10

sporadic = 95%
genetic/familal = 5%

Question 11

describe sporadic (typical MND)

Answer 11

middle/late age onset
slight preference for males to females 1.5:1
UMN +/- LMN loss
muscle weakness, cramps, wasting, paralysis
sensation preserved
death in 2 yrs

Question 12

example of genetic MND

Answer 12

spinal muscular atrophy
progressive loss LMNs
infantine or juvenile
LMN symptoms (weakness, wasting, loss reflexes + fasciculation)
recessive mutation in survival motor neuron gene = codes for SMN protein, important to move RNA in/our nucleus in splicing (floppy baby syndrome)

Question 13

describe the hypothesis of genetic causes of MND

Answer 13

genetic mutations - SMN1, SOD1, TDP43, FUS, VEGF, C90RF72
2% MND due to SOD1 mutation but most research is on SOD 1 mouse (inherited)
90% people aged over 60 yrs, but mice are immature and dead at 4 mnths (early onset)

Question 14

describe the hypothesis of excitotoxicity causes of MND

Answer 14

loss of glial glutatmate transporters
excessive glutamate
acts on NMDA receptors
BUT only some reports of low glut transporters, high glut in CSF
most work been done in vitro
nmda antagonists riluzole only extends life by 90 days

Question 15

describe the hypothesis of oxidative stress causes of MND

Answer 15

SOD 1 (superoxide dismutase 1) scavenges free-radicals
has mutation = inc free radicals
BUT sod1 mutations kills other cells too

Question 16

other hypotheses of causes of MND

Answer 16

smoking, immune, inflammaging + glial cells, mitochondrial abnormalities etc

Question 17

describe mnd research @ UoA

Answer 17

age = key factor that affects nerve injury outcomes
young mns die quickly + large numbers
old mns die slowly + small numbers
olf mns sit in inflamed env unlike young mns