History
Risk factors
The neonate population is highly susceptible to the infection of meningitis due to their underdeveloped immune system. In particular, premature infants are the highest at risk since immunoglobins do not cross the placenta of the mother before 32 weeks gestation. There are other risk factors; however, that contribute to the occurrence of neonatal meningitis [41] :
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Maternal rectovaginal group B Streptococcus colonization
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Maternal fever
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Chorioamnionitis
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Low birth weight (< 1500 g)
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Prolonged or premature rupture of membranes
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Prolonged hospitalization of laboring mother and/or infant
History and Physical Examination
Regardless of the specific pathogen involved, neonatal meningitis is most often caused by vertical transmission during labor and delivery. It occurs most frequently in the days following birth and is more common in premature infants than in term infants. [4] It is closely associated with sepsis.
Risk factors for the development of meningitis include low birth weight (< 2500 g), preterm birth (< 37 weeks’ gestation), premature rupture of membranes, traumatic delivery, fetal hypoxia, and maternal peripartum infection (including chorioamnionitis).
Signs and symptoms of neonatal meningitis are often subtle, making diagnosis difficult that leads to morbidity. Clinical signs of the infection are including but not limited to:
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Fever or hypothermia
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Irritability or lethargy
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Hypotonia
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Feeding intolerance or vomiting
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Respiratory distress
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Apnea
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Bradycardia
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Hypotension
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Poor perfusion
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Seizures
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Bulging anterior fontanel
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Nuchal rigidity
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Jaundice
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Hypo- or hyperglycemia
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Diarrhea
These symptoms are also seen in sepsis, occurring within the first 24 hours of the infant being born. [41] Detection of neonatal meningitis is often late, with signs such as nuchal rigidity, bulging anterior fontanel, and convulsions. These symptoms are a predictor for a poor prognosis for the infant, including severe neurological impairments.
In evaluating a neonate for meningitis, the following 3 key points should be kept in mind:
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It is important to remain vigilant for maternal infection “setups” (eg, prolonged rupture of membranes, fever, and chorioamnionitis) while remembering that asymptomatic maternal infection is always a possibility even with screening
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Early-onset and late-onset bacterial infections have distinctive clinical courses (see below)
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In herpes simplex virus (HSV) infections, the presence of skin lesions in a meningitic neonate is the exception rather than the rule
Bacterial meningitis
Early onset
Symptoms appearing in the first 48 hours of life are referable primarily to systemic illness rather than to meningitis. Such symptoms include temperature instability, episodes of apnea or bradycardia, hypotension, feeding difficulty, hepatic dysfunction, and irritability alternating with lethargy. [1] Respiratory symptoms can become prominent within hours of birth in group B streptococcal (GBS) infection; however, the symptom complex also is seen with infection by E coli or Listeria species.
Late onset
Late-onset bacterial meningitis (ie, symptom onset after 48 hours of life) is more likely to be associated with neurological symptoms. Most commonly seen are stupor and irritability, which Volpe describes in more than 75% of affected neonates. Between 25% and 50% of neonates will exhibit the following neurological signs:
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Seizures
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Bulging anterior fontanel
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Extensor posturing or opisthotonos
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Focal cerebral signs including gaze deviation and hemiparesis
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Cranial nerve palsies
Nuchal rigidity is the least common sign in neonatal bacterial meningitis, occurring in fewer than 25% of affected neonates. [1]
HSV meningitis
Early features of HSV meningitis may mimic those associated with bacterial meningitis, including pallor, irritability, high-pitched cry, respiratory distress, fever, or jaundice, progressing to pneumonitis, seizures, hepatic dysfunction, and disseminated intravascular coagulopathy (DIC). [16]
Complications
Regardless of etiology, meningitis in neonates can progress rapidly to serious complications, including cerebral edema, hydrocephalus, hemorrhage, ventriculitis (especially with bacterial infection), abscess formation, and cerebral infarction.
Cerebral edema, hydrocephalus, and hemorrhage each may cause increased intracranial pressure, with potential for secondary ischemic injury to the brain because of decreased brain perfusion:
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Cerebral edema results from vasogenic changes, cytotoxic cell injury, and, at times, inappropriate antidiuretic hormone (ADH) secretion
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Hydrocephalus results from debris obstructing the flow of cerebrospinal fluid (CSF) through the ventricular system or from dysfunction of arachnoid villi; it occurs in as many as 24% of neonates with bacterial meningitis [22]
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Hemorrhage occurs in regions of infarction or necrosis and should be suspected in a neonate with new focal neurological findings or clinical deterioration
Ventriculitis results in sequestration of infection to areas that are poorly accessible to systemic antimicrobial drugs. Inflammation of the ependymal lining of ventricles often obstructs CSF flow. Thus, all of these complications are interactive, making effective management difficult. Ventriculitis occurs in as many as 20% of infected neonates. [23] Failure to respond to appropriate antibiotic therapy and signs of elevated intracranial pressure (ICP) may suggest the diagnosis. [24] Intraventricular administration of antibiotics may be necessary in cases of ventriculitis.
Cerebral abscess occurs in as many as 13% of neonates with meningitis. [22] New seizures, signs of elevated ICP, or new focal neurological signs suggest the diagnosis. Brain imaging with contrast is essential for making the definitive diagnosis. Surgical intervention may be required.
Cerebral infarction, both focal (arterial) and diffuse (venous), may complicate recovery. Autopsy studies have found evidence of infarction in 30-50% of specimens studied. [1] Imaging studies suggest that the actual incidence of infarction may be even higher. [25] Meningitis has been shown to be associated with 1.6% of all cases of neonatal arterial stroke and 7.7% of venous infarcts. [26]
Necrotizing lesions secondary to HSV meningitis can be deleterious to the developing brain.
Other, longer-term complications that may develop include residual epilepsy, cognitive impairment, hearing loss, visual impairment, spastic paresis, and microcephaly. Some of these disorders may be difficult to detect during infancy.
Hearing, for example, is difficult to evaluate without the child’s cooperation, and even then, assessment may be limited to behavioral response to sounds. Brainstem auditory evoked response (BAER) testing does not evaluate all dimensions of hearing, but this test, which can be performed reliably in sedated infants, only slightly overestimates hearing loss, which occurs in 30% of survivors of bacterial meningitis and 14% of survivors of nonbacterial meningitis. [27] Subtle impairment of sound discrimination may not be readily apparent.
Similarly, cognitive impairment may not be evident until the child has started school or advanced into higher grades where more complex analysis of information is necessary. [20] Careful screening for neurological, cognitive, and developmental deficits must be conducted as part of routine pediatric care over a period of many years, and the responsible physician should be attentive to possible problems with perception, learning, or behavior that may result from neonatal infection.
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Acute bacterial meningitis (same patient as in the other two images). This axial nonenhanced CT scan shows mild ventriculomegaly and sulcal effacement.
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Acute bacterial meningitis (same patient as in the other two images). This axial T2-weighted MRI shows only mild ventriculomegaly
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Acute bacterial meningitis (same patient as in the other two images). This contrast-enhanced, axial T1-weighted MRI shows leptomeningeal enhancement (arrows).
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Meninges of the central nervous parts
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Neisseria meningitidis
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Neonate with a lumbar myelomeningocele with an L5 neurologic level. Note the diaphanous sac filled with cerebrospinal fluid and containing fragile vessels in its membrane. Also, note the neural placode plastered to the dorsal surface of the sac. This patient underwent closure of his back and an untethering of his neural placode. The neural placode was circumnavigated and placed in the neural canal. A dural sleeve was fashioned in such a way to reconstruct the neural tube geometry.
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This anteroposterior skull radiograph demonstrates the craniolacunia or Luckenschadel seen in patients with myelomeningocele and hydrocephalus. Mesodermal dysplastic changes cause defects in the bone. The thin ovoid areas of calvaria are often surrounded by dense bone deposits. They are most likely the result of defective membranous bone formation typical of neural tube defects and not increased intracranial pressure as once thought. These characteristic honeycomb changes are seen in about 80% of the skulls in children with myelomeningocele and hydrocephalus
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Sagittal T1-weighted MRI image of a child after closure of his myelomeningocele. Child is aged 7 years. Note the spinal cord ends in the sacral region far below the normal level of T12-L1. It is tethered at the point in which the neural placode was attached to the skin defect during gestation. The MRI showed dorsal tethering, and the child complained of back pain and had a new foot deformity on examination. By definition, all children with a myelomeningocele have a tethered cord on MRI, but only about 20% of children require an operation to untether the spinal cord during their first decade of life, during their rapid growth spurts. Thus, the MRI must be placed in context of a history and examination consistent with mechanical tethering and a resultant neurologic deterioration.
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Sagittal T1 MRI image of a child with a myelomeningocele and associated Chiari II malformation. Note the cerebellar vermis and part of the brainstem has herniated below the foramen magnum and into the cervical canal (arrow). This patient had multiple brainstem symptoms and findings to include stridor and cranial nerve paresis (cranial nerves III, VI, IX, X) despite having a well-functioning ventricular-peritoneal shunt. He required a posterior fossa decompression of his hindbrain in order to relieve the symptoms of hindbrain herniation and brainstem compression. A minority of myelomeningocele patients require a Chiari II decompression. Those that do usually present in their first year of life with similar symptoms, stridor and cranial nerve paresis. A functioning shunt is imperative prior to exploring the posterior fossa in these children. Often times, especially in older children, a shunt revision may alleviate some of the symptoms of hindbrain compression. Tube Defects in the Neonatal Period
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Neonate with a large occipital encephalocele lying in the prone position prior to surgical intervention. Note the large skin-covered sac that represents a closed neural tube defect. Often called cranium bifidum, it is a more serious condition that represents a failure of the anterior neuropore to close. In this patient, a defect in the skull base (basicranium) was associated with this large sac filled with cerebrospinal fluid and a small, disorganized remnant of brain. The patient fared satisfactorily after the surgery in which the encephalocele was excised. However, the patient needed placement of a ventricular-peritoneal shunt to treat the resultant hydrocephalus, which is not uncommon. At age 5 years, the child was doing well and had only moderate developmental delay.
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Autopsy specimen on a child with anencephaly. This is one of the most common CNS malformations in the West. The neonate, like almost all with such a severe forms of neural tube defects, did not survive more than a few hours or days. This malformation represents a failure of the anterior neuropore to close. This photograph also reveals an absence of the calvaria and posterior bone elements of the cervical canal, as well as the deficiency in the prosencephalon. Photo courtesy of Professor Ron Lemire.
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Ventral view of a child with anencephaly that, like the previous picture, shows the loss of cranium and enclosed nervous tissue. In addition to the primary defect in development, a secondary destruction of nervous tissue occurs. Direct exposure to the caustic amniotic fluid causes progressive destruction of the remaining neural structures and secondary proliferation of a thin covering of vascular and glial tissue. Photo courtesy of Professor Ron Lemire.
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These 2 photographs depict the lumbar regions on 2 different children with closed neural tube defects. Both children have lipomyelomeningocele. The child in the left has a dorsal lipoma that is pedunculated. The child on the right has a more common-appearing lipomatous mass that is heaped up beneath the skin. Both lipomas lead from the subcutaneous tissue, through the dura and into the intradural space, where they are attached to the spinal cord. Photos courtesy of Professor J.D. Loeser.
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Photograph of a child undergoing a neurosurgical procedure in which the spinal cord is being detached (untethered) from the intradural and extradural lipomatous mass that fixes it to the subcutaneous tissue. The white arrow shows the laser char on the lipoma that has been shaved off the spinal cord and was connected to the extradural mass. The black arrow shows the extradural lipoma, which crept through the dura and attached to the spinal cord, thereby firmly fixing the spinal cord at too low and too dorsal a location in the sagittal plane.
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The lumbar region of a newborn baby with myelomeningocele. The skin is intact, and the placode-containing remnants of nervous tissue can be observed in the center of the lesion, which is filled with cerebrospinal fluid (CSF).
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Axial T1-weighted MRI scan of an 8-week-old girl who presented with enlarging head circumference. Considerable ventricular dilatation is shown on the lateral and third ventricles. Periventricular lucency is observed around the frontal horns, indicating raised intraventricular pressure.
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Sagittal T1-weighted MRI scan of an 8-week-old girl who presented with enlarging head circumference. The third and lateral ventricles are dilated, whereas the fourth ventricle is of normal size. Aqueductal stenosis is shown. The appearance is typical of this condition.
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Phase-contrast MRI scan of an 8-week-old girl who presented with enlarging head circumference, obtained 3 months after endoscopic third ventriculostomy. A large signal void is shown in the prepontine region, corresponding to the flow through the stoma in the floor of the third ventricle, indicating that the ventriculostomy is functioning well.
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Axial T1-weighted MRI scan of a 15-year-old girl who was born with thoracic myelomeningocele, hydrocephalus, and Arnold-Chiari II syndrome. She was treated with a ventriculoperitoneal shunt. The ventricular system has a characteristic shape, with small frontal and large occipital horns, which are typical in patients with spina bifida. The shunt tube is shown in the right parietal region.
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Sagittal T1-weighted MRI scan of a 15-year-old girl who was born with thoracic myelomeningocele, hydrocephalus, and Arnold-Chiari II syndrome. Significant hindbrain hernia and low-lying fourth ventricle are shown in the context of the Arnold-Chiari II syndrome. Damaged shunt valve removed during shunt revision from a 22-year-old woman with hydrocephalus and spina bifida. The material of the valve has dramatically disintegrated.
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Damaged shunt valve removed during shunt revision from a 22-year-old woman with hydrocephalus and spina bifida. The material of the valve has dramatically disintegrated.
