Bee Sting-Induced Acute Ischemic Stroke: A New Manifestation of Kounis Syndrome?

In the very interesting report published in Annals of Indian Academy of Neurology,[1] a 41-year-old man developed a fatal right middle cerebral artery territory stroke following an attack by more than 50 bees. The authors speculating on the causality of stroke attributed this to either anaphylactic hypotension and reduced cerebral perfusion or to thromboxane and phospholipase induced platelet aggregation and hypercoagulant state and carotid spasm from retrograde stimulation of the superior cervical ganglion.

Indeed, the honey bee sting venom named also Apitoxin (from Latin apis = bee and Greek toxikon = poison) can induce allergic, cardiovascular, and neurotoxic events.[2] Whereas honeybees are one of our planet's most important and hardest working creatures, their sting venom can induce a variety of actions including vasoconstriction of the cerebral arteries. It contains peptides such mast cell degranulating peptide, and melittin, as well as a variety of enzymes such as phospholipase A2, hyaluronidase, phosphomonoesterase acid esterase, α-D-glucosidase, lysophospholipase, α-galactosidase, α-acetylamino-deosiglucosidase, and arylamidase.[3] The mast cell degranulating peptide is a direct mast cell degranulator that triggers mast cells to release various cytokines and chemokines and in particular histamine and enzymes such as tryptase, chymase, and cathepsin-D and arachidonic acid products. Histamine via H1 coronary receptors and chymase together with cathepsin-D by converting of angiotensin I to angiotensin II, which is a major vasoconstricting substance, can induce artery spasm in individuals with even normal arteries. Furthermore, arachidonic acid products including thromboxane can induce platelet activation, with consequent vasospasm and thrombosis.[4]

We agree with the authors’ pathophysiological explanation. However, in our opinion, all above substances participate in the pathophysiology of the allergy and anaphylaxis associated acute coronary syndrome, the so-called Kounis syndrome. Three variants of this syndrome have been described so far, namely, coronary spasm with normal or nearly normal arteries, artery thrombosis, and stent thrombosis.[4] This syndrome is caused by a variety of allergens, including drugs, several conditions, and environmental exposures such as bee stings on several occasions.[5]

Symptoms involving organs other than the heart might also occur in patients with conditions characterized by acute mast cell mediator release, as in systemic mastocytosis and mast cell activation disorders.

We have come across 2 patients, with mast cell-related disorders, who developed transient cerebral ischemic attacks [6] while they had the previous history of chest pain and Kounis syndrome. The first developed transient hemiparesis with decreased sensation and muscular weakness of the face and the second developed episodes of sudden transient paresis and numbness of his right arm following strenuous work that was redeveloped during hospitalization.

Recently, we have treated a patient with Kounis syndrome type-I variant caused by wasp sting who developed irreversible diffuse hypoxic-ischemic encephalopathy and he is still, for 6 months, in a vegetative state.[7] Another patient with Kounis syndrome type-II variant caused by an allergic reaction to amoxicillin-clavulanic acid under general anesthesia was complicated with severe, irreversible, and subsequently fatal encephalopathy of ischemic origin resulting from low blood pressure or direct proinflammatory and/or vasoconstrictive mediator action in the cerebral arterial system.[8]

All of the above show that Kounis syndrome is a pan-arterial hypersensitivity-associated disorder that affects not only the coronary arteries but also the cerebral arteries.[9] The latter can be affected via the same mechanism as the coronary arteries through the action of anaphylactic mediators that can induce vasoconstriction, hypo-perfusion, and thrombosis. Physicians should be aware of the various manifestations of this disorder in order to apply prompt and appropriate therapeutic measures.

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