ISSN-Online: 2236-6814

https://doi.org/10.25060/residpediatr



Relato de Caso - Ano 2024 - Volume 14 - Número 4

Neonatal Arterial Ischemic Stroke investigation and management protocol

Neonatal Arterial Ischemic Stroke investigation and management protocol

Nicolas Ramos1; Gustavo Barbosa David1; Simone Cristina Stadnick2,3; Stephanie Ribeiro Raitez3,4

ABSTRACT

OBJECTIVE: To describe the condition, the management of the case and its clinical manifestations in order to alert healthcare professionals regarding the importance of early diagnosis of Neonatal Arterial Ischemic Stroke (NAIS).
CASE REPORT: Male newborn, delivered at a tertiary hospital in the state of Santa Catarina, Brazil, via cesarean section at an early term, with no reported complications. Upon birth, the baby presented with hypotonia, hypoactivity, and weak crying. Subsequently, bradycardia and the need for positive pressure ventilation and hypoglycemia were observed. Within the first hours of life, the baby exhibited tremors in the upper limbs upon stimulation. Laboratory tests did not clarify the situation, therefore blood cultures and cerebrospinal fluid samples were requested. At 24 hours of life, persistent tremors and drooping of the right side of the mouth were noted, raising suspicion of convulsive seizures. Management included phenobarbital to control the symptoms. A head computed tomography revealed hypodensity in the right hemisphere, suggestive of hypoxic-ischemic injury. A brain computed tomography angiography did not reveal any signs. Following discussions with the neuropediatrician and neurosurgeons, the diagnosis of NAIS was established. In the subsequent days, the patient was closely monitored and discharged with instructions on the 35th day of life.
DISCUSSION: NAIS is a prevalent condition among newborns. Howerer, diagnosis rates in Brazil are lagging behind due to the nonspecific clinical manifestations and the insufficient attention to the topic within the medical community. In this context, individuals affected by NAIS endure lifelong consequences.

Keywords: Stroke, Seizures, Neonatology.


INTRODUCTION

Arterial ischemic stroke occurs due to the sudden deprivation of cerebral blood flow, resulting in injury to the neurons1. Neonatal Arterial Ischemic Stroke (NAIS) typically occurs from 20 completed weeks (154 days) of gestation through 28 days after birth2. The prevalence is approximately 1:1,600-5,000 live births3. Identifying this important condition is directly related to the patient's quality of life and is still sparsely discussed in the national literature4.

The clinical manifestations of NAIS may vary, but frequently, they are characterized by onset of seizures within the first 12-72 hours of life, potentially followed by apnea, hypotonia, and lethargy. Early treatment and appropriate care can help minimize the impact of the sequelae and improve the quality of life of affected children5.

It is essential to raise greater awareness about NAIS, in order to improve diagnosis, treatment, and prognosis for affected infants. The present study aims to describe the condition and case management while alerting about signs and symptoms regarding the significance of early diagnosis of NAIS.


CASE REPORT

A 38-week gestational age male infant, appropriate for gestational age, was delivered at a tertiary hospital in Brazil. The baby was born via cesarean section due to a breech presentation. Immediate umbilical cord clamping was performed due to hypotonia, decreased activity, and weak crying, resulting in Apgar score of 6/8/8. In the delivery room, the baby developed bradycardia, requiring Positive Pressure Ventilation. A hemoglucotest (HGT) revealed hypoglycemia, unresponsive to infant formula, necessitating transfer to the neonatal intermediate care unit. Within 24 hours of life, the newborn presented tremors in the upper extremities upon stimulation. Laboratory tests showed leukocytosis (white blood cells 24,170 cells/mm3) without a left shift and hypomagnesemia, with no other significant alterations. No cultures were collected at that time. After intense crying, a decrease in oxygen saturation accompanied by cyanosis occurred, which resolved after administration of 5 liters per minute of oxygen in the incubator.

At approximately 24 hours of life, the patient presented persistent tremors and drooping of the right side of the mouth. The primary hypothesis discussed among the neonatologist team was an epileptic seizure, managed with phenobarbital (20 mg/kg). Blood cultures and cerebrospinal fluid (CSF) samples were requested. The newborn did not show complete improvement, leading to a repeated dose of phenobarbital (10 mg/kg) and the addition of a maintenance dose of 4 mg/kg/day every 12 hours. In the afternoon, the patient experienced a significant episode of hypoglycemia (HGT: 39 mg/dL), corrected with a bolus of 10% dextrose (2 mL/kg). After another episode of hypoxemia refractory to oxygen therapy with a 30% oxygen hood, an urgent transfer request was made to the Neonatal Intensive Care Unit (NICU), where nasal continuous positive airway pressure was initiated, leading to hypoxia correction. Assistance from the neuropediatrics service was requested.

The head computed tomography showed hypodensity in the right hemisphere with sulcal effacement and midline shift, suggestive of hypoxic-ischemic injury (Figure 1). The brain computed tomography angiography did not reveal any signs of aneurysmal dilation of arterial stenosis. The CSF analysis and blood cultures yielded no significant abnormalities. After consulting with the neurosurgery team, a diagnosis of ischemic stroke in the right middle cerebral artery territory with mass effect was established. Decompressive craniectomy was not performed. The newborn was monitored and remained stable, ultimately being discharged from the hospital on the 35th day of life.



Currently, the patient is under the care of the speech therapy, physiotherapy, neuropediatrics, and specialized stimulation services. In recent examinations, the patient has been diagnosed with microcephaly as a consequence of NAIS. New seizure episodes have occurred, requiring an increase in the dosage of the current anticonvulsant medications.

Maternal history: The mother is 20 years old and has a medical history of chronic arterial hypertension, type 2 diabetes mellitus, hypothyroidism and obesity. Throughout the pregnancy, the mother was on continuous medication, including metildopa, insulin, and levothyroxine. Adequate prenatal care was provided, with negative serological tests and no specific screening for Group A beta-hemolytic Streptococcus conducted.


DISCUSSION

Neonatal Arterial Ischemic Stroke (NAIS) is the most common cerebrovascular event in the perinatal period, typically occurring from 20 weeks of gestational age through 28 days of life2. It is defined as a localized interruption of cerebral blood flow secondary to thromboembolic phenomena, resulting in tissue ischemia. The prevalence is around 1:1,600-5,000 live births3.

In term-born infants, 57-70% of NAIS cases occur in male individuals. This finding may be related to different neuroprotective responses between the sexes. In females, estrogen was shown to have a neuroprotective effect6. Other risk factors are associated with maternal factors and placental disorders, such as primiparity, oligohydramnios, chorioamnionitis, premature rupture of membranes, coagulation disorders, and preeclampsia7. Conditions related to the intrauterine-to-extrauterine transition have also been described, including Apgar scores below 7 at 5 minutes of life and the need of neonatal resuscitation8.

Concentration of pro- and anticoagulant proteins change during pregnancy and the postnatal period, with activation of both fetal and maternal coagulation cascades occurring near the time of birth9. Consequently, newborns are particularly susceptible to ischemic stroke due to the combination of maternal risk factors and coupled with the physiological placental and perinatal activation of coagulation mechanisms2.

Embolisms entering the fetal circulation would be redirected from the right to the left heart through the foramen ovale. In the fetal systemic circulation, a large proportion of blood flow is directed to the brain due to its high demand10. In this model, the event would occur before or immediately after birth, prior to the closure of the foramen ovale. Following arterial occlusion, a cascade of cellular and molecular events take place from the hypoxic-ischemic (HI) injury2.

The literature presents the left hemisphere as predominant in 80% of NAIS cases. Uncertain hypothesis suggest that the left carotid artery has a more straight anatomy, which may facilitate thrombus displacement through this pathway10.

NAIS is associated with various clinical presentations. It can even be asymptomatic, making it challenging to suspect and resulting in high rates of underdiagnosis2. Seizures represent the primary clinical manifestation of cerebral involvement, found in 25-40% of affected individuals5. Neonatal epileptic seizures can originate from hypoxic-ischemic encephalopathy (HIE), a primary differential diagnosis. However, HIE occurs in the context of neonatal asphyxia, with multisystemic manifestations that must meet the criteria established by the American Academy of Pediatrics11. Other non-specific manifestations of NAIS include hypotonia, lethargy, apnea, encephalopathy, feeding difficulties, and alterations in muscle tone5.

To confirm the diagnosis, a comprehensive approach is essential, as outlined in Figure 2.



Brain magnetic resonance imaging is considered the preferred diagnostic test due to its capability to detect early-stage ischemic lesions. Brain Magnetic Resonance Angiography should be conducted to identify the site of arterial occlusion. Differential diagnosis should include: neonatal encephalopathy, stroke, central nervous system infection, metabolic disorders (hypoglycemia, hypocalcemia and hypomagnesemia), trauma12.

Appropriate treatment and monitoring measures should be promptly initiated, preferably in an NICU. However, the therapeutic approach for NAIS is still sparsely discussed in the literature, lacking well-defined protocols and guidelines. Current studies emphasize the importance of supportive care to ensure neonatal homeostasis, such as controlling oxygenation, hydration, electrolyte balance, temperature, hyper/hypoglycemia, blood pressure, and blood indices. Anticoagulant therapy is not widely employed due to the low risk of recurrent stroke. This therapy demonstrates potential benefit for neonates at high risk of recurrent stroke, attributable to documented thrombophilia or the presence of complex congenital heart disease (with the exception of patent foramen ovale). Thrombolytics and mechanical thrombectomy are rarely indicated considering the lack of evidence for its use. In patients with seizure symptoms, antiepileptic therapy is initiated to prevent parenchymal lesions, with phenobarbital and levetiracetam being the most commonly used drugs12,13.

The evaluation of thrombophilia in neonates proves to be clinically limited, since the levels of protein C, protein S, antithrombin and factor XI, inherently reduced to 30% of adult levels. Carrying out thrombophilic tests during the neonatal period can lead to misinterpretations12.

Alternative treatments, including therapeutic hypothermia have been tested and proven itself effective for patients with cerebral lesions. A pre-clinical study showed that TH reduced the volume of some NAIS ischemic lesions and improved cerebral metabolic activity14. Also, the use of sedo-analgesia (SA) to mitigate the effects of cerebral stress has not yet been evaluated in the context of NAIS. Recent data suggest that SA seems to benefit infants with HIE in the first 72 hours of life15.

Although the mortality rate is considered low, 60%-80% of children will experience some type of sequelae in the future, such as epilepsy, intellectual, behavioral, and language deficits3,5. An integral aspect of achieving optimal neuropsychomotor development within individual capabilities involves the necessity of a multidisciplinary team.


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1. Centro Universitário para o Desenvolvimento do Alto Vale do Itajaí, Acadêmico do Curso de Medicina - Rio do Sul - Santa Catarina - Brazil
2. Centro Universitário para o Desenvolvimento do Alto Vale do Itajaí, Professor do Curso de Medicina - Rio do Sul - Santa Catarina - Brazil
3. Hospital Regional Alto Vale, Departamento de Neonatologia - Rio do Sul - Santa Catarina - Brazil
4. Hospital da Criança Santo Antônio - Santa Casa, Departamento de Neuropediatria - Porto Alegre - Rio Grande do Sul - Brazil

Correspondence to:
Nicolas Ramos
Centro Universitário para o Desenvolvimento do Alto Vale do Itajaí
Rua Dr. Guilherme Gemballa, 13 Jardim América
Rio do Sul - Santa Catarina - Brasil
E-mail: nicolas.ramos@unidavi.edu.br; nicolaswramos@hotmail.com

Submitted on: 11/09/2023
Approved on: 23/01/2024