Since 1903, when Morax and Marie proposed their theory of centripetal migration of the tetanus toxin, it has been taught that spread to the nervous system occurs via the peripheral nerves, the toxin ascending in the axis cylinders or the perineural sheaths. Modern studies, using fluorescein-labeled tetanus antitoxin, have disclosed that the toxin is also widely disseminated via blood or lymphatics, probably accounting for the generalized form of the disease. However, in local tetanus (see Chap. 45), the likely mode of spread to the CNS is indeed by retrograde axonal transport.
Mode of Action of Tetanus Toxin
Like botulinum toxin, the tetanus toxin is a zinc-dependent protease. It blocks neurotransmitter release by cleaving surface proteins of the synaptic vesicles, thus preventing the normal exocytosis of neurotransmitter. The toxin interferes with the function of the reflex arc by the blockade of inhibitory transmitters, mainly GABA, at presynaptic sites in the spinal cord and brainstem. The Renshaw cell, the source of recurrent inhibition of spinal and brainstem motor neurons, is preferentially affected. Elicitation of the jaw jerk, for example, is normally followed by the abrupt suppression of motor neuron activity, manifested in the electromyogram (EMG) as a “silent period” (see further on). In the patient with tetanus, there is a failure of this inhibitory mechanism, with a resulting increase in activation of the neurons that innervate the masseter muscles (trismus, or lockjaw). Of all neuromuscular systems, the masseter innervation seems to be the most sensitive to the toxin. Not only do afferent stimuli produce an exaggerated effect, but they also abolish reciprocal innervation, allowing both agonists and antagonists to contract, giving rise to the characteristic muscular spasm of tetanus (see below). In addition to its generalized effects on the motor neurons of the spinal cord and brainstem, there is evidence that the toxin acts directly on skeletal muscle at the point where the axon forms the endplate (accounting perhaps for localized tetanus) and also upon the cerebral cortex and the sympathetic nervous system in the hypothalamus. Many of these features have been reviewed by Sanford.
The incubation period varies greatly, from one or two days after exposure to a month or longer. Long incubation periods are associated with mild and localized types of the disease.
There are several clinical types of tetanus, usually designated as local, cephalic, and generalized.