Pathophysiology of tetanus spasms:
The tetanus toxin initially binds to peripheral nerve terminals then it
retrogradely goes to CNS attaches with gangliosides at presynaptic
inhibitory motor nerve endings, blocks glycine and gamma amino butyric
acid (GABA) across the synaptic cleft. Thus, the excitatory impulses are
out of control by any excitatory impulse. The generalized muscular
spasms characteristic of tetanus is produced. The toxin appears to act
by selective cleavage of a protein component of synaptic vesicles,
synaptobrevin II, and this prevents the release of neurotransmitters by
the cells4.
The mortality in tetanus is high if patient experiences respiratory
spasms. But patient doesn’t get spasms (especially respiratory spasms)
since the start of disease process. This means the inhibitory glycine
and GABA or dopamine across the synaptic cleft from cerebellum, midbrain
and basal ganglia controls the agonist and antagonist muscle via its
regulatory factors, which inhibits the spasm since the start of disease.
With increasing amount of toxin from the bacteria these
neurotransmitters get depleted. When this store gets exhausted, the
spasm gets clinically evident, in the form of opisthotonos and later
respiratory muscle spasm and eventually death.
As we know dopamine is being synthesized in Substantia Nigra and Red
Nucleus region of Midbrain and then travels via Striatonigral pathway to
basal ganglia and also to cerebellum. From where it travels down to
Renshaw cells in the Anterior Horn Cells of spinal cord and regulates
the overexcitotory impulses causing decrease in spasm. Thus, this
circuit is just the natural circuit of body which is being used to
suppress the spasm naturally. So, by giving centrally acting dopamine
agonists (Levodopa with carbidopa) the natural body’s inhibitory
neurotransmitter store is restored to normal which causes decrease in
respiratory spasms and saves life. This single pilot case study
hypothesizes the fact that with the supply of these neurotransmitters
(dopamine) the spasm should get relieved immediately and thus the life
saved. We have used the combination of carbidopa and levodopa to these
patients to decrease the spasms specially the respiratory spasm which is
the main cause of death in tetanus cases.
Passive immunization with human tetanus immune globulin (TIG) shortens
the course of tetanus and may lessen its severity. A dose of 500 U may
be as effective as larger doses. Therapeutic TIG (3,000-6,000 units as 1
dose) has also been recommended for generalized
tetanus5.