Tetanus

Why did this condition - all on its own - merit an entire chapter of Oh's Manual?  One might conjecture that tetanus, though essentially unknown in the developed west, is still prevalent in the rest of the world and therefore worth mentioning in any textbook which lays claim to global appeal. As an introduction to tetanus, Oh's is comprehensive. But, for those of us who have little time, the LITFL review of tetanus is an excellent condensed resource. And for those of us with infinite time, the references below are comprehensive and most importantly interesting. Question 12 from the second paper of 2013 and Question 6 from the second paper of 2017 explored this issue extensively, and it may come up again even though its relevance to metropolitant Australian intensive care may be minimal 

In short: after spending some of its life cycle in dirt or faeces, C.tetani spores find their way into an open wound, and take root there. It used to be rusty nails animal bites and battlefield injuries, but these days body modification piercing (particularly of mucous linings) is the prevalent cause. The spores reproduce. Approximately 10-15 days after the first infection, they generate the "vegetative form" which is the true bacillus; this form secretes tetanospasmin, the tetanus toxin responsible for the horrific signs and symptoms.

Signs of tetanus

The first few signs and symptoms are:

• Neck stiffness
• Sore throat
• Difficulty opening the mouth

The latter is due to masseter spasm.

Later, more muscle groups become involved, in a roughly descending manner.

• Contraction of facial muscle groups, giving rise to trismus and the rictus of tetany, known generally as the risus sardonicus.
• Descending patterns of muscle rigidity, progressing from the head, down
• Characteristic spasms:
  • Flexion and adduction of the arms
  • Extension of the legs
  • Opisthotonos
  • Potentially, these spasms could involve the larynx and the diaphragm, and therefore ventilation may become necessary
  • They are intermittent, and they may be spontaneous or triggered by touch, visual, auditory, or emotional stimuli.
  • The muscle contraction during these spasms is of such strength that bones may break and tendons may be avulsed from their insertion sites.
• Autonomic dysfunction
  • This takes somewhat longer to develop
  • Typically, it manifests as an increase in sympathetic tone - hypertension, tachycardia, ileus and urinary retention.
  • After the respiratory failure, this autonomic madness is what actually kills people.

These signs and symptoms all arise from the effect of tetanus toxin on synaptobrevin, a protein which faciliates the binding of neurotransmitter vesicles to the presynaptic membrane. The consequence is a cessation of neurotransmission - particularly of GABA.

The decrease in inhibition is equivalent to excitation. This mechanism is well described in a review article form the BMJ. The decrease in GABA activity accounts for the increase in motor tone, and for the dyregulation of postural and autonomic reflexes. The tetanus toxin also acts as an inhibitor of presynaptic acetylcholine release at the neuromuscular junction, which under normal circumstances might produce flaccid paralysis (like botulinum toxin) - but the central disinhibition overrules any peripheral neuromuscular junction dysfunction, and rigidity still ensues.

Differential diagnosis of tetanic rigidity

There are several syndroms which can also account for whole-body rigidity, opisthotonos and trismus. These were asked about in Question 6 from the second paper of 2017.

• Intracranial catastrophe - increased tone an all 4 limbs should make on think of something happening in the brain stem. The generally increased tone and the spasming arm flexion makes one think of decerebrate posturing. However one does not normally develop a risus sardonicus while having a bilateral brainstem lesion. Most relevantly, one should not be fully alert during an episode of decerebrate posturing.
• Strychnine poisoning - but where does one get a hold of strychnine these days? It is no longer available widely; nowadays most countries which still use it tend to limit its sales. In California, for example it is used as a mole and gopher poison.
• Local temporomandibular disease, causing masseter spasm
• Local oral disease causing masseter spasm,
• Epilepsy
• Stiff person syndrome

Confirmation of the diagnosis of tetanus

• Clinically:  the physical findings are quite characteristic. Henderson et al (1998) described a case series where only one case in eleven was misdiagnosed in the ED. "Laboratory results and cultures are of little diagnostic value", the authors concluded.
• The "spatula test" which is where you poke the patient's posterior pharyngeal wall to elicit a masseter spasm; Apte & Karnad (1995) found it had 100% specificity and 94% sensitivity. 
• Wound culture might occasionally grow C.tetani (in 30% of cases)
• Serum antitoxin level: you can't test for the actual tetanospasmin, but you can test for the antitoxin immunoglobulin; levels above 0.1 IU should be protective, so very low levels demonstrate susceptibility and therefore raise the level of clinical suspicion.

Management of tetanus

• Control the airway. Usually, there will be laryngospasm, and respiratory failure with stridor.
• Disable the toxin: passive immunisation with tetanospasmin antibodies
  • this will bind circulating toxin only;
  • all the toxin already within the CNS will continue to have its effects, i.e. the symptoms will not resolve
• Destroy the bacterium and its spores: both are sensitive to metronidazole, and thus there is usually a good response. Benzylpenicillin is also added.
• Control the spasms. Usually a neuromuscular junction blocker or benzodiazepine infusion is needed.
• Control the sympathetic nervous system. Usually, an infusion of labetalol, magnesium sulfate or clonidine is required.