Blackwell Publishing LtdOxford, UKNANNeuropathology and Applied Neurobiology0305-1846Blackwell Publishing Ltd, 20062006326625634Original ArticleParoxysmal coughing, subdural and retinal bleedingJ. F. Geddes and D. G. Talbert Neuropathology and Applied Neurobiology (2006), 32, 625–634 doi: 10.1111/j.1365-2990.2006.00771.x Paroxysmal coughing, subdural and retinal bleeding: a computer modelling approach J. F. Geddes* and D. G. Talbert† *London W4, and †Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, London, UK J. F. Geddes and D. G. Talbert (2006) Neuropathology and Applied Neurobiology 32, 625–634 Paroxysmal coughing, subdural and retinal bleeding: a computer modelling approach Unexplained subdural and retinal haemorrhages in an iological variables monitored. It showed that coughing infant are commonly attributed to ‘shaking’, the mecha- causes intracranial pressures to build up exponentially to nism of which is believed to be traumatic venous rupture. approach a maximum, proportional to the amount of However, the haemorrhagic retinopathy reported as a pressure the musculature of the thorax can produce, as result of Valsalva manoeuvres and the subdural bleeding venous return is impeded. They do not have time to that is a rare complication of pertussis together demon- become dangerous during individual coughs, as blood strate that if a sustained rise in intrathoracic pressure is quickly returns after the cough is over, reestablishing nor- transmitted to cerebral and retinal vessels, it may result in mal pressures. Paroxysmal coughing, however, does not bleeding, similar to that reported in inflicted injury. Such allow blood to return between coughs, with the result that haemorrhages would be expected to occur whenever very high luminal pressures may be generated, sufficient severe paroxysmal coughing were induced, whatever the to damage veins. A history of coughing, vomiting or chok- cause. This study used a computer modelling approach to ing is not uncommon in otherwise normal infants with investigate feeding accidents as the trigger for bleeding. A retinal and subdural bleeding. Our findings suggest that dynamic circulatory model of a 3-month-old infant was paroxysmal coughing could account for such bleeding in induced to ‘cough’, and the response to changes in phys- some cases. Keywords: paroxysmal coughing, retinal haemorrhage, subdural haemorrhage structural brain damage [1,2] cannot rupture bridging Introduction veins without first causing severe structural neck injury The pathogenesis of infantile retinal and subdural bleed- and traumatic brain damage [3–5]. Impact to the head is ing is as yet unresolved, although most physicians remain a much more likely cause of subdural haemorrhage [3,6], convinced that ‘shaking’ is the principal cause, once a because it results in greater movement of the brain and number of rare alternative explanations have been distorts the immature skull [7,8]. Nevertheless, despite excluded. In such a scenario, vigorous to-and-fro move- this evidence, the accepted medical opinion is still that ments of the brain inside the skull rupture bridging veins – unexplained subdural and retinal bleeding in an infant a mechanism extrapolated from the acute subdural hae- showing no signs of impact are most likely to be due to matomas that occur in accidental trauma in older chil- ‘shaking’. dren and adults. However, recent biomechanical work Subdural and retinal haemorrhages are not diagnostic strongly suggests that shaking at levels known to cause of abusive injury, neither alone nor in combination, and there are clearly several mechanisms by which they may occur. They have been reported in accidental trauma [9]. Correspondence: JF Geddes. E-mail: [email protected] They have also been documented to occur in a range of © 2006 Blackwell Publishing Ltd 625 626 J. F. Geddes and D. G. Talbert clinical situations in which trauma is not involved, in One condition in which raised pressure in the system which one or more of a number of different factors leads to a whole range of mechanical complications, including coagulopathy, cerebral atrophy, extreme central including intracranial bleeding, epistaxis, conjunctival venous congestion, raised intracranial pressure and pro- and periorbital petechiae, is pertussis. Bordetella pertussis found hypoxia may be aetiologically significant, according attaches to cilia, disabling them, and so allowing mucus to to the clinical situation [10,11]. Both subdural and retinal accumulate in the airways. The resulting irritation causes bleeding also occur after a proportion of normal deliveries, powerful paroxysms of coughing, with marked swings in neonates and in premature babies [12–14] though no in intravascular pressure. Serious secondary complica- study has ever attempted to assess whether both may be tions such as intracranial haemorrhage were regularly present together in this particular cohort. Of particular reported when whooping cough was more common than interest is how otherwise normal young children may it is today. The emphasis in the early literature is that present with subdural and retinal bleeding, without evi- meningeal bleeding, particularly in the subdural space, dence of any of the above factors, if not from being was the most usual type of intracranial haemorrhage ‘shaken’. [22–25]. Full post mortem reports that include a neuro- On anatomical and physiological grounds alone, sub- pathological examination are unusual, but a detailed dural and retinal bleeding could occur when raised early description of a child who died of pneumonia follow- intrathoracic or intra-abdominal pressure is transmitted ing severe pertussis documented bilateral subdural bleed- to the intracranial circulation [15]. The olfactory and ing, in addition to cortical venous thrombosis and venous visual systems evolved as extensions of the brain and so infarction [26] and though exceedingly rare, subdural derive their circulation from intracranial vessels. Ethmoi- bleeding remains a recognized sequela of the paroxysmal dal arteries, the retinal arteries, and the arteries to perior- coughing of pertussis today [20,27,28], with or without bital skin are all branches of the ophthalmic artery, which brain swelling. Subconjunctival haemorrhages are regu- arises from the internal carotid; the corresponding veins larly reported in severe cases of pertussis, and although drain into the cerebral venous system. The result is that retinal bleeding probably also occurs there are again no luminal pressures in retinal and nasal vessels follow those reports in the literature documenting fundal or histologi- within the brain. Raised pressure within the chest and cal examinations of the eye in pertussis patients who have abdomen in Valsalva manoeuvres restricts blood flow back had subdural haemorrhage. to the heart and increases the pressure within retinal In a significant proportion of cases in which abuse is veins, resulting in retinal bleeding [16–18]. The actual alleged because retinal and subdural bleeding have been incidence of such an occurrence is unknown, because found, there is a preceding history of aspiration of feed, haemorrhages sparing the macula may be asymptomatic, choking or vomiting, with paroxysmal coughing. Could and only severe cases get reported. Whether there is such a history be aetiologically relevant? Investigation of simultaneous leakage of subdural blood is also unknown, the pathophysiology of cough-related injury is difficult: because all the recorded cases of Valsalva retinopathy are the rarity of infantile subdural and retinal bleeding pre- of course adult, and the situation will be different in a cludes observational studies, and infant experimentation fused skull, where vessels are unable to distend to the same is impossible. Variations between species render animal extent as in infants. Patients with very thin subdural hae- models unreliable. We have adopted a computer modelling matomas do not have symptoms of an acute intracranial approach, using a model of an infant which can be bleed and so would not be investigated, but the same induced to ‘cough’ in a variety of patterns, and in which mechanism – transmission of raised intrathoracic pres- the resulting vascular pressures can be monitored and sure to the brain – has been implicated as a cause of sub- compared with those thought sufficient to produce parox- dural bleeding [19,20]. Indeed, having studied the ysmal cough injury (PCI) [15]. structure of cerebral bridging veins in detail, Yamashima and Friede concluded that ‘not only sudden acceleration Hypothesis or deceleration of the head but also sudden increases in venous pressure can lead to an augmentation of tension That paroxysms of coughing from any cause, including especially at the subdural portion of the bridging veins, from aspiration of feed or vomit, can generate sufficient thus inducing subdural bleeding’ [21]. rise in vascular luminal pressure to cause PCI, a pattern of © 2006 Blackwell Publishing Ltd, Neuropathology and Applied Neurobiology, 32, 625–634 Paroxysmal coughing, subdural and retinal bleeding 627 intracranial and intraocular bleeding identical to that of Our infant model ‘CALEB’ was originally developed the ‘shaken baby syndrome’. from the feto-placental model ‘Fetal Charlotte’, which has been described in detail elsewhere [29]. Fetal Charlotte has been applied to the study of gestational problems Methods where there would be ethical and experimental restric- CALEB is a mathematical software model of