Perinatal stroke

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Perinatal stroke is a disease where an infant has a stroke between the 140th day of the gestation period and the 28th postpartum day, [1] affecting up to 1 in 2300 live births. [2] This disease is further divided into three subgroups, namely neonatal arterial ischemic stroke, neonatal cerebral sinovenous ischemic stroke, and presumed perinatal stroke. [3] Several risk factors contribute to perinatal stroke including birth trauma, placental abruption, infections, and the mother's health. [4]

Contents

Detection and diagnosis of perinatal stroke are often delayed due to prenatal onset or inadequacy of neonatal signs and symptoms. [5] A child may be asymptomatic in the early stages of life and may develop common signs of perinatal stroke such as seizures, poor coordination, and speech delays as they get older. [6] Diagnostic tests such as magnetic resonance imaging, electroencephalogram, and blood tests are conducted when doctors suspect the patients have developed signs of a perinatal stroke. [7]

The prognosis of this disease is associated with the severity and the development of the symptoms. [4] This disease can be treated by anticoagulant and anticonvulsant drugs, surgical procedures, and therapeutic hypothermia, depending on the condition of the patient. [8]

Types of perinatal stroke

Neonatal arterial ischemic stroke

Ischemic Stroke Stroke ischemic.jpg
Ischemic Stroke

A neonatal arterial ischemic stroke occurs when the blood vessels of the brain are partly or completely blocked. This situation normally affects the middle cerebral arterial region. [9] This subgroup of perinatal stroke affects between 5 and 43 babies in 100,000 live births. [10] A recent multinational cohort study showed that stroke or succeeding deficits caused the death of 65% of the patients who were suffering from neonatal arterial ischemic stroke. [11] Risk factors such as maternal fever, [12] gestational diabetes and having a record of miscarriage experiences will increase the occurrence of neonatal arterial ischemic stroke. [13] However, the definitive etiology of neonatal arterial ischemic stroke remains uncertain to date. [1]

Neonatal cerebral sinovenous ischemic stroke

Neonatal cerebral sinovenous ischemic stroke is a disease in the cerebral venous system caused by thrombosis. [14] Thrombosis in this region will hinder outflow from the venous system, causing a surge in the central venous pressure. [15] This will lead to intracranial hypertension, cerebral ischemia or wide spreading hemorrhage which may result in a permanent neurologic deficit [16] or mortality. [14] This disease has an incidence rate of between 2.6 and 2.69 in every 100,000 babies per year. [17] However, mortality due to neonatal cerebral sinovenous ischemic stroke is rather rare. [18]

Presumed perinatal stroke

Presumed perinatal stroke is a condition when the stroke is only diagnosed after the neonatal period and does not have any significance in neurological examination within the 28 days after birth. [19] The majority of infants who were later diagnosed with presumed perinatal stroke were free of symptoms during the neonatal period. [20] The timing that a stroke occurs varies between the 140th day of the pregnancy period and the 28th postpartum day among those infants suffering from presumed perinatal stroke. [1] These infants normally suffer from arterial strokes or white matter venous infarctions that may have variability in underlying mechanisms, risk factors, and outcomes. [21] [22]

Causes

Perinatal stroke is correlated with various risk factors in infants including birth trauma, placental disorders, infections, and the mother's health. [4]

Birth trauma and mechanical trauma to the fetal head and neck can cause stroke by damaging arteries: Some children may have arteries that are damaged by trauma or inflammation leaving a rough or jagged inner lining where blood clots can get stuck. These clots can build up enough so that eventually the artery is clogged and no blood can flow through. [23] In addition to vascular damage, trauma to the fetal head from excessive uterine activity, manipulation, pressure, and forceps or vacuum application via direct occlusion or vasospasm can cause perinatal ischemic stroke. [24]

Hypoxic-ischemic encephalopathy (HIE), [25] also known as birth asphyxia arises from oxygen deprivation in the womb. HIE results from placental abruption, umbilical cord problems, uterine rupture, or the failure to identify abnormal heart rate by the medical staff. [26]

Placental disorders associated with perinatal stroke, range from anatomical (site or degree of implantation) such as placenta previa [27] to placenta-maternal effects (fetal erythroblastosis). [28]

Infections like chorioamnionitis cause an infection in the maternal blood, commonly leading to premature birth and the newborn experiencing brain damage, meningitis, or death. [29] Other infections include neonatal sepsis, where the immune system reacts by affecting their organs and tissues resulting in meningitis, seizures, and cerebral palsy. [30]

The mother's health is also associated with perinatal stroke, some factors include blood clotting disorders, congenital heart diseases, and prenatal cocaine exposure. [31] Blood clotting disorders such as Hemophilia A and B result from low clotting factor quantities leading to heavy bleeding.[ medical citation needed ] In congenital heart disease, perinatal stroke results from the disruption of blood flow from obstruction of a blood vessel in the brain. [3] [32]

However, various infants still experience perinatal stroke after a normal pregnancy and studies have shown that sometimes there is a lack of direct cause and many infants are idiopathic. [31]

Signs and symptoms

Neural Activity During a Seizure Depiction of neural activity during a seizure.gif
Neural Activity During a Seizure

Many infants are asymptomatic until they are older. Symptoms such as speech delays, balance difficulties, and asymmetrical weakness become more apparent and are signs that they experienced a stroke. [4] In asymmetrical weakness, infants favor one hand over the other due to cerebral palsy which arises from lesions to the central nervous system. [33] Infants who do give indications of stroke in the womb or shortly after birth commonly experience seizures. [3] When an infant has a seizure, they experience jerking in the face, legs, or arms, alongside delayed breathing. [4] Seizures are mostly caused by hypoxic-ischemic encephalopathy (HIE) or perinatal asphyxia. [34]

Diagnosis

Doctors can use diagnostic tests to determine if an infant is having a stroke. After a clinical presentation of a stroke, the first diagnostic tests used are imaging techniques. Further diagnostic tests such as EEG, Echo, blood tests, and genetic tests are carried out depending on the symptoms portrayed by the newborn. [7]

Imaging Techniques

Magnetic Resonance Image of Brain After Stroke Head MRI stroke.JPG
Magnetic Resonance Image of Brain After Stroke

Perinatal stroke can be diagnosed with medical imaging techniques that present the brain's image. The usage of diffusion-weighted imaging with magnetic resonance imaging is effective for early diagnosis of perinatal stroke. [18] Computerized tomography (CT) is also a commonly used diagnostic technique for this disease. [35] These medical imaging techniques can show bleeding or blockage in the brain and detect damage caused by ischemic stroke or hemorrhages to the brain tissues. [36] Magnetic resonance imaging is clinically preferred to computerized tomography as it can highlight the brain's blood flow. [35] In addition, perinatal stroke is challenging to classify on computerized tomography as the neonatal brain has higher water content. [7] [36] However, in certain situations, such as the inability to transport unstable infants with severe respiratory or cardiac disorders from the intensive care unit, cranial ultrasound is used as an alternative to magnetic resonance imaging. [7] Cranial ultrasound can identify intracranial hemorrhage, intraventricular hemorrhage, large cerebral sinus venous thrombosis along with the brain's blood flow. [7]

Electroencephalogram

Seizures associated with perinatal stroke are normally focal and include rhythmic contractions of the arm or leg. [7] Findings on EEG portray slow, isolated spike-wave patterns from the region of the dead tissue resulting from blood supply failure. [37]

Echocardiogram

Abnormality in the heart rate can be detected by an echocardiogram which creates a detailed image of the heart by utilising sound waves. This method locates the clot's source in the heart, which migrated to the brain and resulted in a stroke. [36]

Blood Tests

Blood tests examine various factors leading to perinatal strokes such as signs of infections, clotting conditions, and coagulation disorders. These include tests for clotting disorders such as thrombophilia and inflammatory disorders. [36]

Genetic Tests

Genetic tests examine the hereditary risk factors for blood clots leading to stroke. Genetic screening is recommended for patients who have a family history of thrombophilia. [38]

Prognosis

Perinatal stroke's severity determines its prognosis. 61% of infants who experienced a perinatal stroke are also diagnosed with cerebral palsy. [4] While, infants with greater stroke severities and involvement of structures such as the precentral gyrus and Wernicke's area have a critical prognosis. [39] Infants who survived a perinatal stroke may develop disabilities like cerebral palsy, sensory dysfunctions, ADHD, and visual or hearing difficulties. [39] As the prognosis is correlated with the progression of the symptoms, treatments allow the infants to recover quickly and reduces the chance of them suffering any long-term disabilities.

Treatments

In clinical practice, there are only limited treatments available for treating perinatal stroke. [40] Medications are commonly prescribed to alleviate some symptoms caused by the disease, while surgery and therapeutic hypothermia will be required to treat hemorrhagic stroke during the perinatal stage.

Medications

Anticoagulants are medications that interfere with the synthesis and function of several clotting factors present in the blood. [41] These medications are commonly used to decrease the possibility of further blood clotting in the babies’ brain who have a medical history of perinatal stroke. [42] These drugs are taken upon expression of identifiable risk factors of perinatal stroke such as multiple cerebral emboli or severe thrombophilia. [43] Examples of anticoagulants used are heparin and aspirin. [7] Some common side effects of anticoagulants are low platelet counts, gastrointestinal bleeding or stomach ulcers. [44] [45]

Anticonvulsants are drugs that alter the level of neurotransmitters (GABA) at synapses between neurons. [46] They also affect the concentration of ions in the neurons by altering the activity of (Na+, K+, Ca2+, Cl-) ion channels in the neuronal cell membrane. [46] These modifications alter the electrical impulses conductivity by amplifying inhibition or reducing the excitation of the neurons. [47] Anticonvulsants such as benzodiazepines, phenytoin, and carbamazepine are commonly used in controlling epilepsy due to perinatal stroke. Adverse effects of these medications include headaches, dizziness and vision problems. [48] [49]

Illustration of Decompressive Craniectomy Surgery Decompressive Craniectomy.png
Illustration of Decompressive Craniectomy Surgery

Surgery

Decompression craniectomy is a procedure commonly used to alleviate the pressure in the brain by removing the pooling blood caused by the ischemic stroke during the perinatal stage. [50] The surgeons will first remove the skin and tissues on top of the site of injury, revealing the skull. [51] Then, a small hole will be made on the skull to allow them to stop the bleeding, before sealing it later.

Temporal lobectomy is a procedure that removes parts of the anterior temporal lobe in treating seizures due to perinatal stroke. [52] Patients who have undergone this surgery will be seizure-free and some will show significant improvement in controlling the seizure. [53]

Therapeutic hypothermia

Therapeutic hypothermia is a process that reduces the metabolism and induces self-repairing of the brain by cooling it down. This method will also cause constriction of blood vessels in the brain, reducing the probability of reacting with hyperactive responses that aggravate brain damage. Such a procedure is proven effective in reducing the possibility of major neurological disability and mortality by 25% when carried out 6 hours after birth. [54] This may be problematic for infants that do not express identifiable symptoms of perinatal stroke. A new direction in treating perinatal stroke by combining therapeutic hypothermia and growth factor medications will most likely improve the condition of the infants after suffering from a stroke. [55]

Related Research Articles

<span class="mw-page-title-main">Hypoxia (medical)</span> Medical condition of lack of oxygen in the tissues

Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise.

<span class="mw-page-title-main">Thrombosis</span> Medical condition caused by blood clots

Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus.

Porencephaly is an extremely rare cephalic disorder involving encephalomalacia. It is a neurological disorder of the central nervous system characterized by cysts or cavities within the cerebral hemisphere. Porencephaly was termed by Heschl in 1859 to describe a cavity in the human brain. Derived from Greek roots, the word porencephaly means 'holes in the brain'. The cysts and cavities are more likely to be the result of destructive (encephaloclastic) cause, but can also be from abnormal development (malformative), direct damage, inflammation, or hemorrhage. The cysts and cavities cause a wide range of physiological, physical, and neurological symptoms. Depending on the patient, this disorder may cause only minor neurological problems, without any disruption of intelligence, while others may be severely disabled or die before the second decade of their lives. However, this disorder is far more common within infants, and porencephaly can occur both before or after birth.

<span class="mw-page-title-main">Cerebrovascular disease</span> Condition that affects the arteries that supply the brain

Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. The most common presentation of cerebrovascular disease is an ischemic stroke or mini-stroke and sometimes a hemorrhagic stroke. Hypertension is the most important contributing risk factor for stroke and cerebrovascular diseases as it can change the structure of blood vessels and result in atherosclerosis. Atherosclerosis narrows blood vessels in the brain, resulting in decreased cerebral perfusion. Other risk factors that contribute to stroke include smoking and diabetes. Narrowed cerebral arteries can lead to ischemic stroke, but continually elevated blood pressure can also cause tearing of vessels, leading to a hemorrhagic stroke.

Perinatal asphyxia is the medical condition resulting from deprivation of oxygen to a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain. It remains a serious condition which causes significant mortality and morbidity. It is also the inability to establish and sustain adequate or spontaneous respiration upon delivery of the newborn, an emergency condition that requires adequate and quick resuscitation measures. Perinatal asphyxia is also an oxygen deficit from the 28th week of gestation to the first seven days following delivery. It is also an insult to the fetus or newborn due to lack of oxygen or lack of perfusion to various organs and may be associated with a lack of ventilation. In accordance with WHO, perinatal asphyxia is characterised by: profound metabolic acidosis, with a pH less than 7.20 on umbilical cord arterial blood sample, persistence of an Apgar score of 3 at the 5th minute, clinical neurologic sequelae in the immediate neonatal period, or evidence of multiorgan system dysfunction in the immediate neonatal period. Hypoxic damage can occur to most of the infant's organs, but brain damage is of most concern and perhaps the least likely to quickly or completely heal. In more pronounced cases, an infant will survive, but with damage to the brain manifested as either mental, such as developmental delay or intellectual disability, or physical, such as spasticity.

<span class="mw-page-title-main">Moyamoya disease</span> Disease characterized by constriction of brain arteries

Moyamoya disease is a disease in which certain arteries in the brain are constricted. Blood flow is blocked by constriction and blood clots (thrombosis). A collateral circulation develops around the blocked vessels to compensate for the blockage, but the collateral vessels are small, weak, and prone to bleeding, aneurysm and thrombosis. On conventional angiography, these collateral vessels have the appearance of a "puff of smoke".

<span class="mw-page-title-main">Cerebral hypoxia</span> Oxygen shortage of the brain

Cerebral hypoxia is a form of hypoxia, specifically involving the brain; when the brain is completely deprived of oxygen, it is called cerebral anoxia. There are four categories of cerebral hypoxia; they are, in order of increasing severity: diffuse cerebral hypoxia (DCH), focal cerebral ischemia, cerebral infarction, and global cerebral ischemia. Prolonged hypoxia induces neuronal cell death via apoptosis, resulting in a hypoxic brain injury.

<span class="mw-page-title-main">Periventricular leukomalacia</span> Degeneration of white matter near the lateral ventricles of the brain

Periventricular leukomalacia (PVL) is a form of white-matter brain injury, characterized by the necrosis of white matter near the lateral ventricles. It can affect newborns and fetuses; premature infants are at the greatest risk of neonatal encephalopathy which may lead to this condition. Affected individuals generally exhibit motor control problems or other developmental delays, and they often develop cerebral palsy or epilepsy later in life. The white matter in preterm born children is particularly vulnerable during the third trimester of pregnancy when white matter developing takes place and the myelination process starts around 30 weeks of gestational age.

<span class="mw-page-title-main">Watershed stroke</span> Medical condition

A watershed stroke is defined as a brain ischemia that is localized to the vulnerable border zones between the tissues supplied by the anterior, posterior and middle cerebral arteries. The actual blood stream blockage/restriction site can be located far away from the infarcts. Watershed locations are those border-zone regions in the brain supplied by the major cerebral arteries where blood supply is decreased. Watershed strokes are a concern because they comprise approximately 10% of all ischemic stroke cases. The watershed zones themselves are particularly susceptible to infarction from global ischemia as the distal nature of the vasculature predisposes these areas to be most sensitive to profound hypoperfusion.

<span class="mw-page-title-main">Intrauterine hypoxia</span> Medical condition when the fetus is deprived of sufficient oxygen

Intrauterine hypoxia occurs when the fetus is deprived of an adequate supply of oxygen. It may be due to a variety of reasons such as prolapse or occlusion of the umbilical cord, placental infarction, maternal diabetes and maternal smoking. Intrauterine growth restriction may cause or be the result of hypoxia. Intrauterine hypoxia can cause cellular damage that occurs within the central nervous system. This results in an increased mortality rate, including an increased risk of sudden infant death syndrome (SIDS). Oxygen deprivation in the fetus and neonate have been implicated as either a primary or as a contributing risk factor in numerous neurological and neuropsychiatric disorders such as epilepsy, attention deficit hyperactivity disorder, eating disorders and cerebral palsy.

<span class="mw-page-title-main">Brain ischemia</span> Medical condition

Brain ischemia is a condition in which there is insufficient bloodflow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus leads to the death of brain tissue or cerebral infarction/ischemic stroke. It is a sub-type of stroke along with subarachnoid hemorrhage and intracerebral hemorrhage.

Germinal matrix hemorrhage is a bleeding into the subependymal germinal matrix with or without subsequent rupture into the lateral ventricle. Such intraventricular hemorrhage can occur due to perinatal asphyxia in preterm neonates.

<span class="mw-page-title-main">Intraventricular hemorrhage</span> Medical condition

Intraventricular hemorrhage (IVH), also known as intraventricular bleeding, is a bleeding into the brain's ventricular system, where the cerebrospinal fluid is produced and circulates through towards the subarachnoid space. It can result from physical trauma or from hemorrhagic stroke.

<span class="mw-page-title-main">Cerebral venous sinus thrombosis</span> Presence of a blood clot in the dural venous sinuses or cerebral veins

Cerebral venous sinus thrombosis (CVST), cerebral venous and sinus thrombosis or cerebral venous thrombosis (CVT), is the presence of a blood clot in the dural venous sinuses, the cerebral veins, or both. Symptoms may include severe headache, visual symptoms, any of the symptoms of stroke such as weakness of the face and limbs on one side of the body, and seizures, which occur in around 40% of patients.

Neonatal encephalopathy (NE), previously known as neonatal hypoxic-ischemic encephalopathy, is defined as a encephalopathy syndrome with signs and symptoms of abnormal neurological function, in the first few days of life in an infant born after 35 weeks of gestation. In this condition there is difficulty initiating and maintaining respirations, a subnormal level of consciousness, and associated depression of tone, reflexes, and possibly seizures. Encephalopathy is a nonspecific response of the brain to injury which may occur via multiple methods, but is commonly caused by birth asphyxia, leading to cerebral hypoxia.

Mild total body hypothermia, induced by cooling a baby to 33-34°C for three days after birth, is nowadays a standardized treatment after moderate to severe hypoxic ischemic encephalopathy in full-term and near to fullterm neonates. It has recently been proven to be the only medical intervention which reduces brain damage, and improves an infant's chance of survival and reduced disability.

Neonatal stroke, similar to a stroke which occurs in adults, is defined as a disturbance to the blood supply of the developing brain in the first 28 days of life. This description includes both ischemic events, which results from a blockage of vessels, and hypoxic events, which results from a lack of oxygen to the brain tissue, as well as some combination of the two. One treatment with some proven benefits is hypothermia, but may be most beneficial in conjunction with pharmacological agents. Well-designed clinical trials for stroke treatment in neonates are lacking, but some current studies involve the transplantation of neural stem cells and umbilical cord stem cells; it is not yet known if this therapy is likely to be successful.

<span class="mw-page-title-main">Ulegyria</span> Type of cortical scarring deep in the sulci

Ulegyria is a diagnosis used to describe a specific type of cortical scarring in the deep regions of the sulcus that leads to distortion of the gyri. Ulegyria is identified by its characteristic "mushroom-shaped" gyri, in which scarring causes shrinkage and atrophy in the deep sulcal regions while the surface gyri are spared. This condition is most often caused by hypoxic-ischemic brain injury in the perinatal period. The effects of ulegyria can range in severity, although it is most commonly associated with cerebral palsy, mental retardation and epilepsy. N.C. Bresler was the first to view ulegyria in 1899 and described this abnormal morphology in the brain as “mushroom-gyri." Although ulegyria was first identified in 1899, there is still limited information known or reported about the condition.

<span class="mw-page-title-main">Pediatric stroke</span>

Pediatric stroke is a stroke that happens in children or adolescents. Stroke affects about 6 in 100,000 children.

A neonatal seizure is a seizure in a baby younger than age 4-weeks that is identifiable by an electrical recording of the brain. It is an occurrence of abnormal, paroxysmal, and persistent ictal rhythm with an amplitude of 2 microvolts in the electroencephalogram,. These may be manifested in form of stiffening or jerking of limbs or trunk. Sometimes random eye movements, cycling movements of legs, tonic eyeball movements, and lip-smacking movements may be observed. Alteration in heart rate, blood pressure, respiration, salivation, pupillary dilation, and other associated paroxysmal changes in the autonomic nervous system of infants may be caused due to these seizures. Often these changes are observed along with the observance of other clinical symptoms. A neonatal seizure may or may not be epileptic. Some of them may be provoked. Most neonatal seizures are due to secondary causes. With hypoxic ischemic encephalopathy being the most common cause in full term infants and intraventricular hemorrhage as the most common cause in preterm infants.

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