NMJ DISORDERS

NEUROMUSCULAR CHARACTERISTICS SIGNS AND SYMPTOMS

DISORDER
Immune-Mediated
Myasthenia Gravis IgG attack at nicotinic receptors of Ach receptor Initial S&S: eye muscle weakness, dysphagia,
 Binding of Ab to receptor blocks binding of ACh slurred speech
 Complement-directed attack (destruction of receptor and post- Hallmark S&S: Muscle weakness increasing during
synaptic fold would increase distance between pre- and post- periods of activity, improving after periods of rest
synaptic membrane) Other S&S:
 Ab binding can result in increase in removal of ACh receptors  Ptosis (eye drooping)
Thymus gland (development of immune response)  Diplopia (double vision)
 Abnormal in MG patients (indicative of lymphoid hyperplasia,  Dysarthria (impaired speech)
thymoma or thymus hyperplasia)  Hypernasality
MuSK proteins (shuttling of AChR to aggregate at locations on post-
synaptic cleft)
 Ab tend to attack this protein (20%)
Main points:
Normal amounts of ACh released from presynaptic axon terminal
Reduced binding to receptors  smaller end plate potential and safety
factor of NMJ transmission
Lambert Eaton Myasthenic IgG directed at presynaptic voltage gated Ca2+ channels interfering with Hallmark S&S: Weakness peaks at rest or
Syndrome quanta release of ACh  reduces end plate potential at post-synaptic immediately after waking up in morning (strength
membrane  NMJ transmission failure eventually improves with brief exercise, not
sustained after prolonged effort)
Toxic or Metabolic
Botulism Exotoxin produced by Clostridium botulinum blocking presynaptic Initial S&S: Nausea, vomiting, abdominal pain
release of ACh at both somatic and autonomic synapses  NMJ and Other S&S: blurred vision, diplopia, dysarthria,
parasympathetic blockade progressive descending weakness, death
Types: infantile, wound, food (canned goods) (respiratory muscle paralysis)
Infantile botulism: decreased muscle tone and
movement; weak cry, constipation
Black Widow Spider Venom Alpha-latrotoxin: produces abnormal ACh release  hyperexcitability 
Poisoning progressive failure of NM transmission + paralysis
Induces membrane depolarization, Ca2+ influx
Snake Venom Alpha-neurotoxin (curare-mimetic): bind to post-synaptic muscle ACh
receptor
Beta-neurotoxin: inhibit release of synaptic vesicles from axon terminals
Organophosphates Irreversible inhibitors of AChE (aging of phosphate bond  covalent
bond formation)
Hypermagnesemia Blockade of NM transmission (prevents presynaptic ACh release and No apparent S&S unless serum magnesium is >2
competitively inhibits Ca2+ influx in presynaptic nerve via voltage- mmol/L
dependent Ca2+ channel Initial S&S: Deep tendon reflex attenuation
Severe form at >5 mmol/L: muscle weakness
Congenital (dependent on gene encoding for a specific protein that may affect NMJ transmission)