The Neuromuscular Junction & Its Dysfunction

Case 1: Neuroimmunology

- 25-year-old male - Usually cause unknown

- Generalized body weakness 1) Koch’s Postulates
- Fatigability
- Eyelid drop in the afternoon
- Worse on exertion especially in the Myasthenia Gravis
evening
- Improved upon rest - Flattened post synaptic cleft
- Systemic exam: grossly reduced strength - EMG: decremental response
o When was the exam done?  Complete opposite of Lambert Ethan
o Incremental response
Pyramidal tract o Worse in the morning
- Voluntary movement Age of Onset
- Comes from brain cortex down to spinal
cord - Bimodal age of onset
- Final pathway: cord to muscle for - Female: usually young
contraction - Male: usually old
- Case is unusual
Motor unit
Ocular myasthenia
- Basic unit for movement
- 7 subunits - Parang inaantok
o Anterior horn cell - Usually bilateral
o Nerve root Fatiguability
o Spinal nerve
o Plexus - Usually proximal body weakness
o Peripheral nerve o Go up the stairs
o NMJ o Mag bra
o Muscle fiber At rest:
Neuromuscular Junction - Allow more receptor to be more available
- Point of contact between nerve & muscle to the Ach
- Pre and Postsynaptic cleft Hot bath
Excitation Contrction coupling - They may get paralyzed
Cross bridge cycle & sliding filament theory - Cold: more enervated

MuSK Why? Cold temperature decreases degradation of

ACh by inhibiting AChEsterase
- Will play a role
- Musk myasthenia
o Respond to monoclonal
ALS o Hyperintensity of the corticospinal
tract
- Progressive neuromuscular condition
o Areas of the motor cortex
characterized by combined upper and
o By virtue of dying back
lower motor neuron signs
- ALS plus FDT
- There is an abnormality in the brain as well
o Frontal dementia
- Weakness produced
- Pathology: corticospinal tract – tract for
voluntary movements
- Anterior horn cell seprates upper and
lower
- Problem: denervation
- Main pathophysiology: SOD 1 abnormality
(scavenger of free radical) that relates to
glutamate toxicity
o Lower free radical scavenging
- Fasciculations, muscle twitching, atrophy
- Upper neuron signs: reflex leads to hyper
reflexion, Babinski
- ALS plus syndrome
o Dementia
o PDP
 Prominent in hawai
 Executive functioning
- Epidemiology
o 1-2/100,000
o Males > Females 2:1
o 90-95% sporadic
o 5-10% inherited
o Onset >40 years
o Increase with age
- Preserves eye movement

Aetiology

- Mercury exposure

Pathology

- loss of large motor neuron

- Abnormality in the brain
o Lying on the back condition
o Entire corticospinal tract goes up
to the brain
o Entire pyramidal tract
o Degeneration