Neuroanatomy Lecture #42: Diseases Of The Nmj And The Motor Unit

Front 1

Def of a neurogenic disease

Back 1

One that originates in the nervous pathways (i.e. the motor neuron) that mediate normal muscular contraction and cause muscle weakness

Front 2

Name possible sites of lesions in the motor unit (7)

Back 2

soma, axon, Schwann cell, the nerve ending/terminal, synaptic cleft, the end plate and the muscle fiber

Front 3

Soma/Axon lesions
• Possible causes (4)
• Signs/Sx (4)
• Two examples

Back 3

Soma/Axon lesions
• Possible causes
- drugs, toxins, trauma, diseases

• Signs/Sx (4)
- muscle weakness and atrophy, fasciculations, fibrillations loss of muscle fiber with replacement by fibrous tissue
• Two examples

Front 4

Poliomyelitis
• Caused by this virus
• Preventative measure
• Common site of infection
• Mode of transmission

Back 4

Poliomyelitis
• Poliovirus
• Vaccine (90% Effective)
• motor neurons in the ventral horn of the spinal cord
• p-to-p contact, oral and nasal secretions and fecal matter

Front 5

Schwann cell lesions
• Possible causes (2)
• Ways in which this lesion type is expressed/manifested
• Two examples

Back 5

• Autoimmune diseases, toxins
• Demyelintion
• Guillan-Barr, Diptheria

Front 6

Botulism
• produced by this bacteria
• mode of transmission (3)
• Mechanism of action
• Presentation

Back 6

• Closteridium botulinium
• Transmission (3)
- eating contaminated food, wound infection, consumption of spores
• A toxic protease cleaves the Snap/SNARE protein complex on the postsynaptic membrane and synaptic vesicle, preventing vesicle docking and subsequent ACh release via exocytosis
• Paralysis of all muscles

Front 7

Alpha-Iatrotoxin
• Source
• mechanism of action
• Presentation

Back 7

• black widow spider
• Acts at the nerve endings/terminals where it forms ion-permeable pores leading to an influx of Ca2+ and massive ACh release
• Tetanus – a continuous, painful contraction of the muscle. The muscle is paralyzed form overactivity.

Front 8

Curare
• The alkaloid it contains
• Mechanism of action

Back 8

• D-tubocurarine
• a non-depolarizing muscle relaxant that blocks AChR on the post-synaptic membrane of the NMJ

Front 9

Lamber-Eaton Syndrome
• Due to a lesion at this site of the motor unit
• Associated with this disease and syndrome type
• Primary presentation
• Etiology

Back 9

• Lesion at the NMJ
• Strength of the muscle increases with sustained or repeated contractions
• Associated with oat cell carcinoma of the lung as a paraneoplastic syndrome
• Insufficient release of Ach into the synaptic cleft due the immune system making Abs that cross-link V-gated Ca2+ channels in motor nerve terminals

Front 10

Signs and test of Lamber-Eaton Syndrome
• Affect of strength on an activity
• Affect on reflexes
• How EPPs are affected
• How mini EPPs are effected
• What does an EMG show with low frequency and high frequency stimulations?

Back 10

• Strength increases with activity
• Reflexes are usually decreased
• EPPs have reduced amplitudes
• Amplitude of mini EPPs
• Low frequency stimulation produces a weak response,
High frequency stimulation produces a waxing response

Front 11

Therapy for Lamber-Eaton Syndrome
• 4 treatments – two procedures and two supplements

Back 11

1) Removal of underlying tumor and give immuno suppressive drugs
2) Plasma exchange
3) Calcium gluconate – enhance Ca2+ influx into the nerve terminal
4) 4-aminopyridine – prolongs presynaptic APs to improve NT release

Front 12

Four types of congenital Myasthenia

Back 12

1) ACh-esterase deficiency in the synaptic cleft at the end plate
2) Slow Channel Syndrome
3) Abnormal binding of ACh to nAChR
4) Abbreviated opening time of ACh-gated ion channels

Front 13

ACh-esterase deficiency in the synaptic cleft at the end plate
• Presentation of the EPP
• High frequency motor nerve stimulation produces this result

Back 13

• Compared to a normal EPP, it is longer and prolonged
• Produces temporal summation of EPPs leading to a depolarizing blockade of the muscle

Front 14

Slow Channel syndrome
• Symptoms (2)
• Mode of action

Back 14

• Rapid muscle fatigue and progressive atrophy
• ACh binds to nAChR longer than usual causing prolonged opening of AChR receptor channels. The sustained influx of Na+ leads to a depolarization block

Front 15

Myasthenia Gravis
• These muscles are often affected first
• Main manifestation
• Other manifestations (4)
• Etiology
• Mechanism of action
• Sx
• The disease can be associated w/ this condition

Back 15

• Eye muscles

• weakness of voluntary muscles which improve after rest and worsen with muscle activity

• Diplopia, Ptosis, Difficulty swallowing, Myasthenic crisis/Breathing difficulties
• An Autoimmune disease

• Abs against nAChR are produced that bind to the α-subunit, crosslinking neighboring AChRs. The Abs DO NOT compete w/ ACh for the binding site, just prevent the NT from binding. There is an enhanced endocytosis and destruction rate of nAChR at the end plate membrane but NO enhanced insertion of new nAChRs.

• Weakness in muscles associated with cranial nerves and limb muscles

• Tumors of the thymus gland

Front 16

Sign, Tests and Tx for Myasthenia gravis
• Results of the patient performing repeated movements
• Result seen on an EMG
• Briefly describe the Tesilon Test and the result of someone w/ the disease
• Tx name 5 drugs, their mode of action and a surgical procedure

Back 16

• Increasing muscle weakness
• Waning pattern
• Involves the IV administration of an AChE Inhibitor which for someone w/ the disease, would produce a + test
• Neostigmine and Pyridostigmine are AChE inhibitors.
Prednisone, Azathiopurine and Cyclosporine are immune suppressors
Thyectomy is a surgical procedure that may also relieve sx.

Front 17

Myotonia congenita
• Another name
• Etiology
• Mechanism of action
• Presentation

Back 17

• Chloride Channel Syndrome
• Autosomal dominant disease that leads to fewer chloride channels being present in the muscle cell membrane.
• The low number of chloride channels in the muscle means the resting membrane potential of the muscle membrane is less negative and therefore easier to depolarize. With the prolonged relaxation phase of the muscular contraction, repetitive firing of the muscle fiber results even after motor nerve stimulation stops.
• Slow relaxation of muscles leading to muscle stiffness and hypertrophy

Front 18

Muscular Dystrophies
• Can be categorized as these types of diseases
• Mode of inheritance
• Most common form and the deficient protein involved
• Most common physiological reason behind low mortality rate

Back 18

• myopathic and genetic
• X-linked recessive
• Duchenne’s, dystrophin protein
• Cardiovascular and respiratory insufficiency

Front 19

LMN Syndrome
• Possible causes (3)
• 6 main sx
• Distribution of nAChRs if the syndrome involves denervation of muscle fibers

Back 19

• Viral infections, Trauma, Degenerative diseases
• Paresis, Flaccid paralysis progressing to Muscle atrophy, hypo-/a-reflexia, Fasciculations, Fibrillations,
• If the LMN Syndrome involves denervated muscle fibers, then the pattern of nAChRs is random across the entire surface of the muscle cell

Front 20

Fasciculations
• Def
• Presentation
• its correlation w/ LMN damage

Back 20

• irregular, spontaneous contractions of muscle fibers composing motor units due to sick α-motor neurons
• Produce visible twitches on the body surface
• It is not always a sign of LMN damage

Front 21

Def of Fibrillations

Back 21

Spontaneous contraction of an individual muscle fiber that can be recorded and visualized by EMG. They produce little or no movement in muscle

Front 22

When a muscle is denervated, explain the change in pattern of AChRs. What is the name of the process that takes place?

Back 22

AChRs are normally clustered on the muscle cell membrane near the post-synaptic nerve terminal. When a muscle is denervated and the nerve terminal is no longer present, the txn rate of AChRs have increased and more AChRs are spread throughout the muscle. The AChRs that are normally inserted at the originally location are also more highly sensitive to ACh. The process is called denervation and hypersensitivity.

Front 23

In the following types of motor unit disorder, in which would you find paresis?

• Motor neuron
• Schwann cell
• NMJ
• Muscle

Back 23

All

Front 24

In the following types of motor unit disorder, in which would you find muscle atrophy?

• Motor neuron
• Schwann cell
• NMJ
• Muscle

Back 24

Motor neuron, Schwann cell and Muscle disorders

Front 25

In the following types of motor unit disorder, in which would you find Fasciculations?

• Motor neuron
• Schwann cell
• NMJ
• Muscle

Back 25

Motor neuron and sometimes Schwann cell disorders

Front 26

In the following types of motor unit disorder, in which would you find a decrease in conduction velocity?

• Motor neuron
• Schwann cell
• NMJ
• Muscle

Back 26

Schwann cell disorders and very rarely motor neuron disorders

Front 27

In the following types of motor unit disorder, in which would you find A fluctuating amplitude of electrical response through an EMG recording with repetitive stimulation to a muscle?

• Motor neuron
• Schwann cell
• NMJ
• Muscle

Back 27

NMJ disorders

Front 28

In the following types of motor unit disorder, in which would you find signs of dennervation in an EMG?

• Motor neuron
• Schwann cell
• NMJ
• Muscle

Back 28

Motor neuron and Schwann cell disorders