Underrated: The Handkerchief Stroke

7. April 2015

Unhealthy lifestyles, poor diet and hereditary risk are well-documented causes of blood supply disruption in the brain. Less well studied are infections which precede this event. Harmless colds are potentially followed by fatal stroke.

This headline could evoke fear in paediatricians and parents: “colds are able to ‘trigger’ stroke in children”. This piece of news derives from a study by Heather Fullerton and her colleagues at the University of California. They conducted a search through the database of a large American insurance company looking for children who had had stroke and looked at these in relation to “harmless” infections – not, for instance, sepsis or meningitis. About ten percent of these children had undergone treatment for arterial ischaemia due to infectious respiratory symptoms which had manifested in the last three days before the stroke. In comparison, during the same period one twelfth as many children suffered stroke without having had similar infections.

Even if the relationship is significant, Lars Marquardt from the University of Erlangen-Nuremberg in Germany points out in his comment on the study in “Neurology” in summer last year: “Minor infections are quite common in children, whereas a stroke is fortunately very rare. Parents should therefore not worry themselves over harmless colds”. When considered over the entire year, children with such an infection were at no increased risk.

Flu vaccination against stroke

This study was one of the first to point out a relationship between unwanted microbial invaders and circulatory system dysfunction in children’s brains. Among adults, the relationship between infection and infarct or haemorrhage was ascertained quite some time ago, even though there are still few comprehensive studies on this. What is striking in any case is that the incidence of stroke rises in the cold season.

As a team of authors from Harvard University and the National Institute of Health write in a recent Lancet Review, about a third of stroke patients have no apparent cerebro-vascular risk factors which could indicate the involvement of infectious elements. In actuality, several studies have shown that systemic infection up to four weeks before a stroke doubles or even increases by as much as a factor of fourteen the risk of stroke. With respiratory tract infections in the first three days it is about three times that of a control group. The situation appears similar with undesirable micro-organisms in the urinary tract.

Inflammation ensures the presence of clogged passages

Often, however, neither is the specific pathogen accurately determined, nor is the type of stroke documented as being either haemorrhagic or ischaemic. In most cases, the infection sets an inflammation in motion. In the blood vessels the release of cytokines takes place and a proliferation of smooth muscle cells can also possibly occur. The increased aggregation of platelets could be the outcome of a previous infection. However these mechanisms, due to lack of conclusive data, are for the time being still speculative in nature.

Endocarditis, meningitis, or neuro-syphilis

An infectious endocarditis event, which leads under unfavourable circumstances to cardio-embolic stroke, is one major risk factor. In one study of nearly 3,000 inpatients carrying such an infection, 17 percent of them suffered a stroke. On average, this happened between one and two weeks following antibiotic treatment. A brain embolism following endocarditis may also run an asymptomatic course. In a study of 56 patients with such heart inflammation, a brain MRI scan uncovered an embolism in four out of five cases; in half of these subjects the case was subclinical. Other studies also found a significant share of microhaemorrhages and ischemic lesions. The most important pathogens in such infections are Staphylococcus aureus and ß-hemolytic streptococci.

A similarly significant role is played by bacterial meningitis involving Streptococcus pneumoniae, S. aureus and Pseudomonas aeruginosa. A Dutch study found that among 700 meningitis patients about a quarter of them had brain infarcts. Over the course of several weeks the risk tends to increase even more. Imaging techniques also show signs of vasculitis with expansion and contraction of the arterial vessels. One study involving 114 participants suggests that a bacterial infection of the meninges is associated with a worse prognosis in stroke.

Inflammation events often manifest in medium and large cerebral arteries; such events particularly in young adults are sometimes the result of neurosyphilis. It’s often the case that precisely these patients show no other typical risk factors for stroke. According to a US study, the risk of myocardial infarction with neuro-syphilis is around ten percent.

Viruses, yeasts and parasites

Bacteria aren’t alone: viruses also play a role in the pathogenesis of stroke. Nonetheless, many study results contradict one another here, the outcome being that the role of virus as a trigger for stroke is only rarely clear to be seen. Traces of colonisation of the central nervous system are frequently observable during infection with Herpes viruses. Vascular disorders are a common symptom of the presence of Varicella-zoster virus. Sometimes an incidence of shingles precedes the stroke some weeks or months in advance.

Yeasts acting as an abscess builder in the brain can ultimately lead to the collapse of the supply system of individual brain areas as can parasites. Tapeworms can also establish themselves there. Local inflammation triggers the stroke. Especially in cases involving infants a CNS form of malaria can appear which can prove fatal in a fifth of such cases.

In instances of chronic infections, studies show that Helicobacter pylori, Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Epstein-Barr virus and several herpes virus species play significant roles. They probably trigger inflammation which also has impacts far away from the site of infection.

Antibiotics and anti-coagulant

In order however to determine the diverse forms of associated pathogen in each respective instance, a lumbar puncture is almost always necessary. In many cases, however, this complicated action does not occur when the stroke – which often occurs to the elderly – is associated with other risk factors. Therefore physicians should become aware of previous exanthema, fever or previous infections. Especially when dealing with patients with immunosuppression the spinal fluid should be analysed in the laboratory. If neurological symptoms develop not suddenly but gradually, and possibly be associated with fever, according to experts a brain scan is the better measure to undertake in preference to the removal of spinal fluid when seeking to bring clarity to the clinical picture.

If evidence of an infection is corroborated, prevention therapy takes place for an impending stroke, as does antimicrobial treatment. There is a manifold increase in mortality from brain infarcts involving infectious meningitis. Rapid identification of pathogens and bringing about their expulsion increases the chances of recovery for the patient.

“Microbial” stroke: an increasing trend

Around 85 percent of all strokes occur in underdeveloped countries, where severe infections belong to the “daily business” of medicine. Good studies on the role of microbes in stroke, however, relate for the most part to industrialised countries. Alongside increasing migration, epidemiologists predict, so will the number of strokes with infectious background rise. Assuming increasing numbers of HIV-infected patients, or patients undergoing immuno-suppressive treatment, the risk of additional infections becomes particularly high. Therefore there is an increased need for clarification of the relationship between infection and stroke, so as to combat brain infarction as one of the most common causes of death.

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