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Introduction:
Stroke is one of the major causes of death of adults in the developing world, and is also an important reason of mortality and chronic neurological morbidity in children. Strokes in children always happen in perinatal period. Therefore, we focus on this clinical issue related to perinatal stroke.
The WHO (World Health Organization) definition of stroke is: “rapidly developing clinical signs of focal (or global) disturbance of cerebral function, with symptoms lasting 24 hours or longer or leading to death, with no apparent cause other than of vascular origin”. This definition emphasizes on the causes, symptoms and duration of stroke. However, perinatal stroke is often lack of distinctive symptoms and difficult to determine the duration of time. Therefore, some studies defined perinatal stroke according to the pathological changes. The United States National Institutes of Health drew up a consensus recommendation on the definition of perinatal stroke, which is “there is focal disruption of cerebral blood flow secondary to arterial or cerebral venous thrombosis or embolization, between 20 weeks of fetal life through 28th postnatal day, and confirmed by neuroimaging or neuropathological studies.”
Classification:
The classification of stroke is of great importance to seek the etiology and determine the treatment. There are several classifications of perinatal stroke. For example, according to the pathological changes, it is classified into three major subtypes: hemorrhagic stroke, ischemic stroke and cerebral venous sinus thrombosis. If based on the time of occurrence, perinatal stroke is classified into fetal stroke and stroke after birth.
Incidence:
The incidence of perinatal stroke is about 1 in 1600 to 5000 births, which is difficult to interpret due to the variability of diagnostic standard, number of cases and underlying population. In most studies, the enrollment criteria were defined as the infants with arterial ischemic stroke diagnosed in the neonatal period. More recent studies have included ischemic stroke as well as hemorrhagic stroke by retrospective analysis. Retrospectively diagnosis is more common than acute one, which indicates the incidence of perinatal stroke may be higher than that of in the previous reports.
Risk factors:
The risk factors of perinatal stroke have not been well understood. Most studies are descriptive ones, which could only provide very little information on quantitative risk evaluation, environmental influence, as well as genetic and environmental interactions. In order to facilitate clinical analysis, they are assorted into fetal, neonatal and maternal risk factors respectively.
Clinical manifestation and diagnosis:
The clinical manifestation of perinatal stroke depends on age. Patients who are diagnosed in the newborn period will present with seizures. They may also have symptoms and signs of neonatal encephalopathy, such as lethargy, hypotonia, feeding difficulties or apnea. For the infants with suspected perinatal stroke but diagnosed until several months later, they will manifest focal hand weakness, delayed milestones, and/or with seizures. But it may be more difficult to diagnose in the newborn period because most infants are less likely to exhibit specific symptoms or signs. Therefore, doctors must know more information about maternal and pregnancy disorders, family histories and so on.
Neuroimaging:
The diagnosis of perinatal stroke is primarily based on neuroimaging. The advances of neuroimaging have greatly improved the diagnosis of perinatal stroke. Although the sensitivity and specificity are low, prenatal ultrasound can recognize fetal stroke, and cranial ultrasound can detect neonatal stroke. The greatest advantage is the portability, which allows to image infants without moving them out of intensive care unit.
Computed tomography (CT) is very sensitive to detect hemorrhage, which appears bright on the film. It could differentiate white from gray matter, although the contrast between these two tissues is relatively low compared with MRI. A worrying issue for CT is the exposure dose of radiation to the infants.
Magnetic resonance imaging (MRI) is much better than CT and cranial ultrasound for its tissue characterization for perinatal stroke. It is more sensitive to subtle tissue injury than either CT or cranial ultrasound. And unlike CT, MRI does not involve with the problem of ionizing radiation, which makes it relatively safer. Diffusion weighted magnetic resonance imaging is the golden standard for acute, focal infarction happened in the neonatal brains, and it could provide valuable information according to the event timing. Nevertheless, MRI also has a disadvantage of requiring the infants to be transferred out of NICU to the scanning room, which causes lots of potential safety risks. And MRI is also relatively expensive.
Numerous advances in imaging technology have potential applications to perinatal stroke, including diffusion weighted imaging, perfusion-weighted imaging, single photon emission computed tomography, and so on.
Management:
In 2008, AHA/ACCP guidelines were published with recommendations on the management of perinatal stroke. However, many recommendations are based on case studies and expert consensus. Unfortunately, randomized controlled trials of perinatal stroke are not available right now.
In the acute phase of stroke, supportive treatments such as reducing intracranial hypertension and anticonvulsants may be important. Thrombolysis is not recommended because neither its effectiveness nor safety was demonstrated in neonates. The American College of Chest Physicians (ACCP) recommends administration of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) in those neonates with arterial ischemic stroke and ongoing cardioembolic source. For the remainder, anticoagulation or antiplatelet therapy is not recommended because the possibility of recurrent stroke is very low.
Therapeutic hypothermia has being emerged as a promising neuroprotective therapy. Although the underlying mechanism is not completely understood, it has been accepted widely that hypothermia could decrease brain edema and mitigate the effects of brain ischemia/reperfusion. In animal models, hypothermia also can lower infarct volume, decrease cerebral metabolism, reduce excitotoxicity due to synaptic glutamate overflow, stabilize blood-brain barrier and neuronal membranes, and decrease cerebral edema in the acute phase of stroke. But Meta-Analysis dose not show significant result that hypothermia could improve the severity of stroke. No difference on mortality was observed.
It has been postulated that hyperbaric oxygen therapy (HBOT) may improve the outcome by reducing the swelling of brain. HBOT is used routinely to treat stroke in some medical centers. But systematic review has not found any evidence to show HBOT could improve the outcome of ischaemic stroke when it is applied during the acute phase. Further research is required to determine the role of HBOT in this condition.
Stem cell may be the hope for stroke therapy. Despite of massive basic research, clinical application in newborns with stroke is still scarce.
Outcome:
Perinatal stroke is a common cause of congenital hemiplegia. Motor dysfunction varied widely from mild hand weakness to severe quadriplegia in infants. The incidence of motor disability and cerebral palsy rang from 50% to 78%.