11.1. Introduction
The most common neuromuscular junction disorder encountered in clinical practice is acquired myasthenias gravis. It is physiologically characterized by decreased end plate potentials that fail to generate an action potential. Its primary cause is the reduction and blockade of acetylcholine receptors (AChR) at the post junctional membrane from antibodies directed primarily at the alpha 1 subunit. Recently other antigenic targets have been; identified. The neuromuscular junction disorders are the clinical representation of deficits in:
- Quantal release
- Postsynaptic membrane architecture (destruction)
- AChR conduction parameter dysfunction
- Density of Ach receptors at the neuromuscular junction
- Acetylcholinesterase activity
- Calcium induced releasing factors at the motor nerve terminal. The difference between the membrane potential and the threshold for initiating an action potential in these disorders is the safety factor for neuromuscular transmission.
Different physiological mechanisms for failure of neuromuscular transmission are operative in each disorder of the neuromuscular junction. Specific muscle junctions that are affected, the associated diseases and components of the CNS/PNS that are involved differentiate the entities. In general, patients with neuromuscular junction diseases have no sensory loss (unless peripheral nerves are affected concomitantly) and have intermittent symptoms particularly with exercises. Diaphragmatic and thoracic paralysis lead to hypercarbia which manifests as lethargy, asterixis, dilated cerebral veins and rarely papilledema (young patients). All forms of NMJ disease lead to muscle weakness. The pupils and reflexes are variably involved as is the autonomic nervous system.
Differential Diagnosis of NMJ Disorders
- Neonatal myasthenia (passive transfer of maternal antibodies)
- Congenital Myasthenic Syndrome:
- End-plate choline acetyltransferase deficiency
- Decreased synaptic vesicles
- Reduced quantal release
- Congenital myasthenic syndrome resembling the Lambert–Eaton myasthenic syndrome
- Slow channel syndromes
- Fast channel syndromes
- Primary acetylcholine receptor deficiency with or without minor kinetic abnormalities
- Congenital myasthenic syndrome associated with pectin deficiency
- Acquired myasthenia gravis:
- Classification
- Pure ocular
- Mild generalized (no bulbar dysfunction); severe generalized (bulbar weakness)
- Fulminant (respiratory failure)
- Late severe
- Myasthenia gravis with atrophy
- Lambert Eaton syndrome
- Botulism
- Drug induced/toxins
- Tetanus
- Snake envenomations:
- Elapidae: Cobra, coral snake, krait, mamba
- Hydrophiidae: Sea snake
- Crotalidae: South American rattle snake
- Viperidae: Vipers
- Arthropod envenomation:
- Black Widow spider (female)
- Funnel web spider
- Scorpion toxin
- Tick paralysis
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