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.