NB8-6 - Diseases of the NMJ and Motor Unit Flashcards
C
List the types and subtypes of motor unit diseases. Give common examples of each subtype.
- Neurogenic - lesion of peripheral nerve
- Soma - Lou Gehrig’s (ALS) and Poliomyelitis
- Schwann Cells - Guillain Barre and Diphtheria
- Nerve Ending - botulism, alpha-latrotoxin, beta-bungarotoxin, and curare
- End Plate/Synaptic Cleft - myasthenia gravis, nAChR defects
- Myogenic
- Muscle Fiber - myotonias and muscular dystrophy
Describe the etiology and clinical features of poliomyelitis.
Poliomyelitis is a small RNA virus that is usually transmitted via fecal-oral route and aerosol droplets. This virus primarily attacks the ventral spinal grey matter.
Clinical features are:
- profound asymmetrical muscle weakness with the affected limb developing acute flaccid paralysis (floppy)
- Extensive trunk paralysis may occur
- If it progresses to C3-C5 then ventilation will be needed
List the toxins we need to know that affect the nerve ending, synpatic cleft, and/or end plate. Where do these toxins come from and what are their mechanisms of action?
- Botulinum Toxin - a protease from bacteria botulinum bacteria that prevents neuronal exocytosis, thereby reducing ACh release
- Alpha-Latrotoxin - toxin from black widows that stimulates presynaptic exocytosis causing massive ACh release
- Beta-Bungarotoxin - toxin in snake venom that stimulates neuronal exocytosis leading to a sustained increase in ACh release, eventually leading to ACh depletion
- Curare - blocks nicotinic ACh receptors
Describe the etiology, clinical features, and treatmetns for Lambert-Eaton Syndrome.
Lamber Eaton is an autoimmune disease where the antibodies attack presynaptic v-gated Ca++ channels at the NMJ causing them to cross-link to each other, thereby reducing ACh release. Often seen in patients with pulmonary small cell cancers
Usually presents with muscle weakness and facilitating NM block which can be seen in a 20Hz EMG as the waxing response. The miniEPPs are unchanged but, due to the reduced quantal content, many EPPs will not attain threshold.
Therapies include removal of tumor, immunosuppressive drugs, calcium gluconate (to enhance Ca++ influx), and 4-aminopyridine (K+ channel blocker) to prolong presynaptic AP and improve ACh release.
List the types of congenital myasthenias and their mechanisms of action.
- Deficiency of ACh-esterase at NMJ leads to a larger and prolonged EPP leads to a depolarizatio block. Presents as a single prolonged muscle twitch
- Slow Channel Sydrome is a genetic condition causing prolonged opening of ACh channels which has similar symptoms as a ACh-esterase deficiency
- Binding of ACh to nAChRs is abnormal
- ACh-gated channels have very brief opening times
- Myasthenia Gravis is a chronic autoimmune disease where nAChR antibodies develop and reduce transmission at the NMJ
When in life do congential myasthenias usually present?
Before the age of two, except for myasthenia gravis which presents between the ages of 20-.30 for females and 60-70 for males
Describe the effects of Myasthenia Gravis on the NMJ
- nAChR antibodies bind to alpha subunits of nAChRs in a non-competitive manner and cause neighboring nAChRs to cross-link.
- This leads to enhanced removal of nAChRs from the NMJ (via endocytosis) but no enhanced insertlion, leading to reduced nAChR density at the end plate
- The synaptic cleft itself also begins to widen, increasing the distance ACh has to travel to the end plate, and the junctional folds of the end plate shrink which decreases surface area and total number of nAChRs.
List the clinical features of myasthenia gravis.
- Weakness of somatic muscles with temporary restoration of strength after rest
- 1st symptom is typically diplopia (double vision) occurring in the afternoon and disappearing by morning
- Diplopia duration gradually increases, followed by ptosis (eyelid drooping) which is compensated for by tilting head back and raising eyebrows
How is myasthena gravis diagnosed and differentiated from lambert-eaton?
- Repeated clenching and unclenching of fists leads to rapid loss of strength instead of gain of strength
- Tensilon test - edrophonium (ACh esterase inhibitor) is administered. Muscular strength will temporarily recover with MG and it won’t with LE
- 20Hz EMG will show waning with MG and waxing with LE
- Anti-AChR blood test
- Ice pack on closed eyelids will temporarily restore eyelid retraction ability in MG
What therapies are there for myasthenia gravis?
- Thymectomy could lower nAChR antibody levels
- Immunosuppressing medications such as azathioprine and corticosteroids
- Pyridostigmine, AChE inhibitor
C
Describe the inheritance pattern, cause, and symptoms of myotonia congenita.
- Autosomal dominant disease
- Loss of fuction mutation to gene encoding Cl- channels in muscle membrane, leading to increased excitability
- This can cause a train of APs so that there is essentially no relaxation of the muscle. Just like in fainting goats
Describe the inheritance pattern, cause, and symptoms of muscular dystrophy.
- X-linked recessive disorder
- Loss of function mutation for gene that encodes dystrophin, leading to progressively weakening muscles with onset in early childhood
- Most common symptom is the Gower Maneuver - when a child is asked to stand up from a supine position he has to roll to his stomach, get on his knees, and push his upper body up with his arms
E
Describe how EMGs should appear in normal, denervated, and myopathic muscles.
D
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