Mycotic Cerebral Aneurysm in a Premature Infant.

Mycotic cerebral aneurysms in neonates are extremely rare and can be difficult to diagnose without a high index of suspicion. We describe a 33-week gestation preterm neonate who developed a mycotic cerebral aneurysm leading to death before repair could be performed. We believe this to be the first literature reported case of a mycotic cerebral aneurysm in a preterm infant. This case revives the ongoing question of when to perform a lumbar puncture in a potentially septic or meningitic infant, while also casting light on maintaining a high index of suspicion for rare intracranial diagnoses that require cranial imaging.

INTRODUCTION

Hydrocephalus in the neonatal population is relatively common, especially among premature infants and is often attributed to intraventricular hemorrhage. Neonatal sepsis and meningitis are also common diagnoses in the neonatal intensive care unit, prompting many intensive care nurseries to develop protocols for the prophylactic treatment of preterm infants due to the association of premature labor with chorioamnionitis and neonatal sepsis. When hydrocephalus and neonatal sepsis occur simultaneously, clinicians are required to rapidly establish a diagnosis, especially with the literature showing an earlier treatment of intracranial processes yielding favorable outcomes. In neonates, atypical etiologies need to be considered quickly to further enhance optimal long-term outcomes. Here, we report a case of an acute onset and rapidly progressive hydrocephalus secondary to mycotic cerebral aneurysm in a preterm infant.

CASE REPORT

A 33-week gestation preterm male delivered through precipitous vaginal delivery in the emergency department to a 21-year-old G2P1 female presenting with acute onset of labor with rupture of membranes at home. Birth weight was 1870 g and Apgar scores were 7 at 1 min and 8 at 5 min. Due to immediate respiratory distress, the infant was intubated and mechanically ventilated. One dose of surfactant was given and he was transferred to the neonatal intensive care unit. Caffeine was administered for apnea of prematurity, and ampicillin and amikacin were initiated for concern of neonatal sepsis due to preterm labor and delivery. Within hours, the infant became hypotensive requiring normal saline boluses and a dobutamine drip, prompting an increased concern for sepsis and the addition of cefepime. However, after 3 days, blood cultures were negative, and the clinical condition had improved. Therefore, the antibiotics were discontinued.

On the day of life three, a routine cranial ultrasound was found to be normal. Echocardiogram was also normal with no structural abnormalities. The initial cranial circumference was 31 cm, and the neurological examination after resolution of hypotension was normal with no focal findings. On the day of life six, significant abdominal distention occurred with pain elicited on examination. Necrotizing enterocolitis was suspected, so empiric intravenous vancomycin and meropenem were initiated. However, pneumatosis intestinalis and portal venous gas were not observed on serial abdominal X-rays, and blood cultures never isolated a pathogen. Due to clinical severity, 2 weeks of antimicrobial treatment was given with clinical improvement and enteral feedings by nasogastric tube were started.

On the 18th day of life, the cranial circumference suddenly increased 34 cm. On examination, the anterior fontanelle was bulging, despite the child being alert and active with a normal neurological examination. Cefipime was initiated out of concern of neonatal sepsis and meningitis. Laboratory evaluation for possible sepsis found hypernatremia that was treated with an enteral sterile water drip. The ventricular puncture was performed and cerebrospinal fluid (CSF) collected. No leukocytes were seen in the CSF sample, but glucose was decreased at 20 mg/dl and protein elevated at 128 mg/dl. Cranial ultrasound revealed significant hydrocephalus with no intraventricular hemorrhage or mass seen. Magnetic resonance imaging (MRI) was performed revealing hydrocephalus [Figure 1] and an apparent right frontoparietal cerebral arteriovenous malformation. MR angiography was performed and confirmed a large saccular aneurysm of the right middle cerebral artery [Figure 2]. Three days after collection of the CSF, Candida lusitaniae was isolated, and the blood culture identified methicillin-resistant Staphylococcus epidermidis. Antimicrobial coverage was changed from cefepime to vancomycin and amphotericin B. For a suspected large mycotic aneurysm of the right middle cerebral artery, neurosurgery was consulted. During the period of surgical consideration, the infant abruptly experienced severe apnea, hypotonia, and lethargy with aggressive attempts at resuscitation failing. Rupture of an aneurysm was the suspected cause of death due to the rapid onset of cardiovascular and neurological demise, but an autopsy was refused by the infant’s mother.

Figure 1

Supratentorial hydrocephalus resulting from the middle cerebral aneurysm compression of the third ventricle in a preterm infant. This illustrates that although intraventricular hemorrhage and posthemorrhagic hydrocephalus is a common etiology for hydrocephalus in preterm infants others diagnoses must be considered, especially with acute onset of hydrocephalus

Figure 2

Contrast-enhanced magnetic resonance angiography of the bilateral middle cerebral arteries demonstrating a large saccular vascular aneurysm on the right

DISCUSSION

Intracranial mycotic aneurysms in the general population are rare with rates of 2.6%–6%[1] in autopsy cases and carry a high mortality rate of 80% if ruptured and 30% when unruptured.[2] Cerebral aneurysms of any origin in infants are extremely rare with an estimated overall incidence of 0.005%–6% in some series,[3456] compared to 0.5%–4.6% in the general pediatric population.[7891011] However, data are inconclusive, so many cases go undiagnosed. Mycotic cerebral aneurysms comprise 5%–15% of aneurysms in children under 18 years of age, and some studies report mycotic cerebral aneurysms may even have a higher incidence in children and adolescents compared to adults.[101213] The literature reports many cases of cerebral aneurysms in the term and preterm population, none of which are mycotic. To the best of our knowledge, this is the first reported case of a mycotic cerebral aneurysm in a preterm infant.

The anatomic distribution of aneurysms differs between the adult and pediatric populations. Aneurysms of the anterior cerebral artery are more common in adults, middle cerebral artery aneurysms occur in an equal distribution according to age, and posterior circulation aneurysms are far more common in the pediatric population.[4111214151617] Moreover, aneurysms in the pediatric population predominately occur in males, suggesting a gender predilection.

The diagnostic workup for suspected intracranial aneurysms begins with computerized tomography (CT) scan. However, in infants, especially preterm infants, clinicians often reserve CT for emergent situations weighing the risk of radiation exposure to benefit of diagnostic yield. Cranial ultrasonography is frequently used in preterm infants for the diagnosis of hydrocephalus or intracranial hemorrhage but is not appropriate for suspected mass or vascular anomalies. Infants presenting with neurologic signs or lethargy should have CT evaluation while those with more subtle signs, contrast-enhanced MRI provide accurate diagnostic information without radiation exposure to the growing brain. While conventional angiography remains the gold standard for the diagnosis of cerebral aneurysms at any age, the procedure is technically challenging in preterm infants and complication risk is high. Often, contrast-enhanced MR angiography is substituted for traditional angiography in this population. It should be understood, however, that MR angiography has a high false-negative rate and if symptoms persist and concern is high, further imaging may be needed.

Although a feared complication, rupture of aneurysms in infants is uncommon. Historically, treatment has been open surgical removal or clipping of the affected vessels, but interventional endovascular options have emerged in recent years. Coiling and stent placement through the catheter are viable options in attempt to avoid craniotomy. Treatment options depend on location, anatomy, and shape of the particular aneurysm[11] as well as the patient’s condition at the time of diagnosis. Long-term monitoring is advised.

This patient was initially treated for suspected meningitis due to a bulging anterior fontanelle and suspicious CSF analysis despite the reassuring neurological examination. The absence of fever, seizures, and lethargy exemplifies the ambiguity of symptoms in neonatal meningitis, sepsis, and intracranial lesions. In fact, intracranial lesions in infants can even be asymptomatic. The open fontanelles and nonossified cranial sutures can allow for rapid cranial expansion without overt neurological signs in infants. Furthermore, neurological symptoms in neonates can be subtle, presenting simply as desaturations or apnea. As preterm infants frequently experience such symptoms, the clinicians may not recognize these subtle presenting signs. Rapid onset and progressive hydrocephalus in infants with bacterial or fungal sepsis or meningitis should always raise concern for mycotic aneurysm formation. Controversy exists regarding the management of suspected meningitis in infants. In the age of aggressive antenatal maternal treatment for Group B Streptococcus colonization, the incidence of early-onset meningitis has fallen dramatically prompting the American Academy of Pediatrics to advise limited diagnostic evaluation in infants with only perinatal risk factors for early-onset sepsis.[1819] Conversely, lumbar puncture should always be performed in infants with symptomatic late-onset sepsis, positive blood cultures, new-onset neurologic symptoms, or acute status change unexplained by alternative diagnosis, as long as the patient can tolerate the procedure.[20] However, should every infant with meningitis receive CT or MRI? Clinicians must remain vigilant and maintain a high index of suspicion to ensure rapid diagnosis and management of intracranial processes in preterm infants. Prior negative imaging studies should not deter from a suspicion of new infectious or bleeding etiologies, and radiographic imaging studies should be rapidly performed as early intervention and management of intracranial aneurysms yield more favorable outcomes.

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Conflicts of interest

There are no conflicts of interest.