Motor Control And Movement Disorders

Front 1

where are motor neurons located?

Back 1

spinal cord: motor nuclei ('anterior horn cells')

brain stem: 9/12 nerves carry axons: III, IV, V, VI, VII, IX, X, XI, XII

Front 2

types of motor neurons

Back 2

- alpha motorneurons

- y motor neurons

Front 3

what is a motor unit comprised of?

Back 3

- axon, soma, neuromuscular junctions/endplates, muscle fibres

Front 4

the two major types of motor units

Back 4

'FF' type: fast twitch, fatigable

'S' type: slow twitch, don't fatigue as quick

Front 5

what is the final common path?

Back 5

- where all converging inputs from various parts of the brain and inputs, interact

Front 6

descending tracts converging on alpha motoneurons...

Back 6

- cortico-spinal (pyr.)

- rubro-spinal

- vestibular-spinal

- reticulo-spinal

Front 7

peripheral receptors

Back 7

- group Ia afferent fibres frommuscle spindles

Front 8

types of paralysis

Back 8

- monoplgeia: one arm or one leg

- hemiplegia: one arm, one leg on same side

- paraplegia - both legs

- quadraplegia - all four limbs

- paresis - partial paralysis

Front 9

abnormalities of muscle tone -->

Back 9

hypertonia: spasticity after stroke or rigidity

- due to increased muscle tone

Front 10

ataxia

Back 10

- form of incoordination

- movements are no longer smooth

- movements can be jerky

Front 11

damage to muscle fibres

Back 11

- myopathies: muscular dystrophy, myotonia

- myasthenia gravis

- botulism

Front 12

muscular dystrophy

Back 12

- group of inherited disorders characterised by deficits in muscle proteins and progressive muscle wasting and weakness

- DOESNT affect motor neurons

Front 13

most common form of muscular dystrophy in children

Back 13

Duchene Muscular Dystrophy (DMD)

- results from mutation in gene coding for muscle 'cytoskeletal' protein: dystrophin

Front 14

most common form of muscular dystrophy in adults

Back 14

myotonic muscular dystrophy (NMD)

Front 15

myotonia

Back 15

- delayed relaxation of muscle after a strong contraction

- muscle retains its stiffness - can take up to a minute to relax

Front 16

mechanism of myotonia

Back 16

- calcium is taking out very quickly of the endoplasmic reticulum - and what we need to stop the contraction is calcium

- inherited (dominant): up to 2000 'triple' (CTG) repeats in chromosomes 19 coding for a protein kinase mytonin

Front 17

myasthenia gravis

Back 17

- muscle weakness (without wasting)

- an autoimmune disease

- few ACh binding sites leads to EPPs (end plate potential) decrease which leads to synaptic transmission decrease

- junctional folds are much smaller than normal

Front 18

botulism

Back 18

- botulinum toxins are produced under anaerobic conditions

- 1 microgram injected into an adult will kill

Front 19

effects of botulism

Back 19

- muscle paralysis due to decrease ACh release
which affects both striated and smooth msucles

- disruption to autonomic nervous system (dry mouth, postural hypotension etc)

Front 20

mechanism of botulism

Back 20

- toxins bind to nerve terminals - internalized by endocytosis and cause proteolysis of several membrane proteins that are involved in vesicle docking and neurotransmitter release (SNAP-25 and syntaxin) --> less ACh release as less terminals and less neurotransmitter release

Front 21

application of botulism

Back 21

- botox: Very mild

- dystonias: a persistent increase in muscle tone and involuntary movements - it can suppress unwanted movement

- hyperhidrosis: can stop excessive sweating

- gastrointestinal and urinary disorders: excessive tone of smooth muscle

- migraine

Front 22

damage to axons and 'walerian degeneration'

Back 22

can happen as a result of injury

- the peripheral part of the axon degenerates quickly

Front 23

changes in the distal part of an axon following a lesion

Back 23

- loss of synaptic transmission

- gengeration (within days)

Front 24

changes in the soma following lesion to axon

Back 24

chromatolysis

- axon regeneration (1-2mm/day) - faciliated by arrays of Schwann cells (only in favourable conditions)

- form a tunnel that is used by regenerating axons

- re-innervation of muscles in some cases, functional recovery

Front 25

when can regeneration of axons occur in the CNS

Back 25

- can be very hard to achieve regeneration of central axons due to the big difference in responsiveness

Front 26

Polio

Back 26

- acute degeneration of motor neurons resulting from a viral infection

- can cause selective damage and death to various groups of motor neurons

Front 27

can polio be used as a treatment?

Back 27

- in phase 1 trials at Duke university - used to treat glioblastomas

- found dramatic shrinking

Front 28

ALS

Back 28

AmyotrophicLateral Sclerosis

- causes weakness and wasting of skeletal muscles and can lead to complete muscle paralysis

Front 29

incidence of ALS

Back 29

- approx 5 in 100,000

Front 30

symptoms of ALS

Back 30

- progressive wasting/weakness/atrophy of muscles --> paralysis

- difficulty with speech, swallowing, impariment of respiration

- muscle stretch reflexes - exaggerated and increased muscle tone (spasticity)

Front 31

signs of muscle denervation

Back 31

- fasciculations: twiches of some motor units which survived atrophy

- fibrillations: spontaneous action potentials generated in individual muscle fibres (ALS will have these even at rest)

Front 32

cause of ALS?

Back 32

- progressive degeneration of Motoneurons in spinal cord and brain stem (combined this is LMN) and increased stretch reflexes and spasticity in UMN

Front 33

Oxidative stress hypothesis

Back 33

- damage of neurons by free radicals --> radical production exceeds detoxification capacity of certain enzymes

Front 34

excitotoxic hypothesis

Back 34

- excessive activation of AMPA and/or NMDA receptors by Glu

Front 35

TDP-43/FUS mutation

Back 35

these are noramlly found in nucleus

the genes coding for these proteins mutate in some forms of familial ALS -the proteins shift to the cytoplasm where they form insoulble aggregates --> affect motorneuron function

Front 36

treatmets for ALS?

Back 36

Riluzole (blocker of Glu release)

Dexpramipexole (improving mitochondrial function)

paclophen (agonist of GABA-B receptors) - reduce spasticity

stem cell treatment:

Front 37

what are the consequences for a hemisection of the spinal cord?

Back 37

- monoplegia: no voluntary functions to the affected side as there is a loss of excitatory inputs to motoneurons from the corticospinal and rubro-spinal tracts

- loss of pain and temperature to contra-lateral side to damage

- loss of fine tactile perception and proprioception below injury on same side

Front 38

consequence of an acute complete transection of the spinal cord?

Back 38

- period of areflexia: spinal shock - lasts 1-3 days

- paralysis from below the injury

- total loss of sensation for below injury

- no muscle reflex

- blood vessels below injury dilate --> low BP

- no more sweating

- no control of bladder and bowel

- dysfunction of sexual organs

Front 39

what does recovery after complete transection involve?

Back 39

- recovery is partial

- recovery of muscle tone

- hyperactive muscle stretch - spasticity

- reflex emptying of bladder and rectrum

- BP increases

- flexor (withdrawal reflex) after several months

- parasthesisa

Front 40

paraspthesia

Back 40

-abnormal sensations from affected areas such as burning

Front 41

mechanisms of recovery from spinal injury

Back 41

- sprouting of presynaptic terminal: re-programming of remaining axon connections

- denervation super sensitivity: increase in receptor expression/traffiking - why some function comes back

Front 42

respiratory management for quadriplegic patients

Back 42

- artificial ventilation

- breathing pacemakers