Neonatal Meningitis

Back

Background

Although the occurrence of neonatal meningitis is uncommon, it remains a devastating infection with high mortality and high morbidity. Neonatal meningitis is often caused by group B streptococcus and is associated with prematurity, gestational age, postnatal age, and geographic region. In order to improve prognosis of the infection, early diagnosis and prompt treatment are crucial to prevent mortality and the incidence of neurologic sequelae that cause long-term neurodevelopmental disabilities. 

Despite the development of effective vaccines, useful tools for rapid identification of pathogens and potent antimicrobial drugs, neonatal meningitis continues to contribute substantially to neurological disability worldwide.

The persistence of neonatal meningitis results from increases in the numbers of infants surviving premature delivery and from limited access to medical resources in developing countries. In addition, the absence of specific clinical findings makes diagnosis of meningitis more difficult in neonates than in older children and adults. Moreover, a wide variety of pathogens are seen in infants as a consequence of the immaturity of their immune systems and intimate exposure to possible infection from their mothers.

This review focuses on common presentations of treatable bacterial and viral meningitis in the neonatal period, defined as the period from birth to 44 weeks after conception. Common central nervous system (CNS) infections caused by bacteria and viruses (eg, herpes simplex virus [HSV]) are emphasized. Meningitides caused by HIV and fungi are excluded, as are those caused by other organisms implicated in congenital CNS damage (eg, cytomegalovirus [CMV] and Toxoplasma).

For patient education resources, see the Brain and Nervous System Center, as well as Brain Infection.

Pathophysiology

Neonates are at greater risk for sepsis and meningitis than other age groups are because of the following deficiencies in humoral and cellular immunity and in phagocytic function:

Etiology

Common bacterial pathogens

Among US neonates, group B streptococci (GBS) are the most commonly identified causes of bacterial meningitis, implicated in roughly 50% of all cases. Escherichia coli accounts for another 20%. Thus, identification and treatment of maternal genitourinary infections is an important prevention strategy.[5]  Listeria monocytogenes is the third most common pathogen, accounting for 5–10% of cases; it is unique in that it exhibits transplacental transmission.[6]

Studies suggest that in underdeveloped countries, gram-negative bacilli—specifically, Klebsiella organisms and E coli —may be more common than GBS. In a series from Africa and South Asia, Tiskumara et al noted that 75% of cases of late-onset meningitis were due to gram-negative bacilli.[7] In a review of studies from Asia, Africa, and Latin America, Zaidi et al reported that the most common organisms were Klebsiella species, E coli, and Staphylococcus aureus.[8]

With the widespread use of intrapartum antibiotic prophylaxis since 1996 in developed countries, the incidence of early-onset GBS infection has decreased, whereas the incidence of late-onset disease has remained fairly constant.[9] However, from 2003 to 2006, the Centers for Disease Control and Prevention (CDC) reported a slight increase in early-onset disease in the United States, particularly in the African American population; the reasons for this are unclear.[10]

Herpes simplex virus

As many as 95% of viral infections caused by HSV result from intrapartum transmission, with occasional postnatal exposure occurring through oropharyngeal shedding or cutaneous shedding of virus by parents or hospital contacts. Late presentation in the second postnatal week is more commonly seen than early presentation of disseminated disease.

Emerging pathogens

As cases of neonatal enteroviral sepsis and aseptic meningitis come to be more frequently recognized, reporting and identification of more virulent serotypes as they affect infants are likely to play a growing role.[11] As many as 12% of neonates may be infected with this family of viruses. Although many of these babies are asymptomatic, enterovirus may be responsible for as many as 3% of neonates who present with a sepsislike picture.[12] More recently, human parechovirus-3 has been implicated in an increasing number of neonates with meningitis. While related to the enterovirus family, this pathogen is not detected with enteroviral polymerase chain reaction (PCR) studies performed on cerebrospinal fluid (CSF).[13, 14]

Enterobacter sakazakii has been identified as an emerging pathogen in neonates. This bacterium is most typically associated with the ingestion of contaminated reconstituted formula. It has been reported with increasing frequency in the past few years, prompting the US Food and Drug Administration (FDA) to publish warnings of possible contamination of dried formula.[15]

Epidemiology

Geographic region is a significant factor in the occurrence of neonatal meningitis. Due to the lack of resources and access to health care in developing countries, the incidence of neonatal meningitis is much higher as compared to developed countries.[41]

Due to the progress of medicine in developed countries, the incidence of neonatal meningitis is estimated to be 0.3 per 1000 live births, as observed in the United States, Sweden, The Netherlands, England, and Wales.[4] The incidence of HSV meningitis is estimated to be 0.02–0.5 cases per 1000 live births.[16] Because of testing limitations, the worldwide incidence of neonatal meningitis is difficult to determine with accuracy. However, a study of neonatal infections in Asia (based on data collected from China, Hong Kong, India, Iran, Kuwait, and Thailand) reported estimated incidences of neonatal meningitis that ranged from 0.48 per 1000 live births in Hong Kong to 2.4 per 1000 live births in Kuwait.[7] Another publication that looked at neonatal infections in Africa and South Asia reported figures ranging from 0.8 to 6.1 per 1000 live births.[17]

These numbers are believed to underestimate the true incidence of neonatal meningitis in underdeveloped countries, given the lack of access to health care facilities in these areas.

Prognosis

Survivors of neonatal meningitis are at significant risk for moderate to severe disability. Some 25-50% have significant problems with language, motor function, hearing, vision, and cognition[18, 3] ; 5-20% have future epilepsy.[19, 20] Survivors are also more likely to have subtle problems, including visual deficits, middle-ear disease, and behavioral problems.[21] As many as 20% of children identified as normal at 5-year follow-up may have significant educational difficulties lasting into late adolescence.[18]

Poor prognostic indicators include low birth weight, prematurity, significant leukopenia or neutropenia, high levels of protein in the cerebrospinal fluid (CSF), delayed sterilization of the CSF, and coma.[1, 2] Seizures lasting longer than 72 hours and the need for inotropes predict moderate-to-severe disability or death with 88% sensitivity and 99% specificity.[5]

Bacterial meningitis

In developed countries, mortality from bacterial meningitis among neonates declined from almost 50% in the 1970s to less than 10% in the late 1990s. However, a corresponding decrease in morbidity rate did not occur.[9]

In a prospective sample of more than 1500 neonates surviving to the age of 5 years, the prevalence of motor disabilities (including cerebral palsy) was 8.1%, that of learning disability was 7.5%, that of seizures was 7.3%, and that of hearing problems was 25.8%.[21] No problems were reported in 65% of babies who survived GBS meningitis and in 41.5% of those who survived E coli meningitis.

HSV meningitis

Mortality among neonates with HSV infection of the CNS is 15%. Of these cases, 25-40% will have culture-proven CSF infection. The 2 HSV serotypes (HSV-1 and HSV-2) carry the same risk of mortality. However, HSV-2 is more commonly associated with morbidity, including cerebral palsy, mental retardation, seizures, microcephaly, and ophthalmic defects.[16] Although the use of acyclovir has reduced the morbidity and mortality associated with HSV infection, neurological sequelae are likely in 50% of neonates with HSV meningitis.[16]

Patient Education

It is encouraged that pregnant mothers undergo prenatal screening and are administered a group B Streptococcus vaccine to combat the risk of neonatal meningitis. Since this infection is so lethal, prevention is the primary approach and this is optimized by the utilization of vaccines against group B Streptococcus.

Since listeria is another bacteria known to cause neonatal meningitis, pregnant mothers should avoid foods that have the potential to be contaminated by listeria. This includes processed meat, soft cheese, coleslaw, and paté[42] . Listeria monocytogenes can be transmitted transplacentally, so pregnant mothers should be aware of the types of food that they are eating. 

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] :

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:

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:

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:

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:

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.

Approach Considerations

Delayed diagnosis of neonatal meningitis is a potentially critical pitfall. Failure to perform a lumbar puncture and detect infection in a neonate with mild fever and minimal, nonspecific clinical findings is problematic; all neonates in whom meningitis might be the cause of symptoms should undergo CSF examination. Delay in treatment because of equivocal laboratory screening tests or because findings are altered by prior partial treatment may cause significant harm.

In a 2001 survey of pediatricians, “meningitis or other infectious disease” and “newborn conditions other than congenital vision/hearing loss” were the 2 most frequent bases reported for malpractice suits.[28] In this survey, “the most prevalent condition for which claims were filed against pediatricians was neurological impairment of an infant. Thirty percent of claims paid were for this condition alone. However, the second most prevalent condition, meningitis, resulted in a higher percentage of paid claims (46%) and a higher total and average indemnity.”

Laboratory Studies

Suspected bacterial infection is often, but not uniformly, confirmed by positive results from cultures of cerebrospinal fluid (CSF) or blood. CSF cultures should be obtained in all symptomatic infants; despite the close relationship between bacterial sepsis and meningitis, it has been estimated that 15-30% of infants with CSF-proven meningitis will have negative blood cultures.[29]

A study from Duke emphasized that with the exception of CSF culture, no single CSF value can be relied upon to exclude neonatal meningitis.[30] The onus is on the clinician to justify initiation of antimicrobial and antiviral therapy, regardless of the CSF values.

Polymerase chain reaction (PCR) assay is a powerful diagnostic tool with excellent sensitivity and specificity. It permits identification of group B streptococcal (GBS) antigen in urine or CSF, and it is the standard for identification of herpes simplex virus (HSV) and enterovirus in CSF. In neonates, PCR is 71-100% sensitive for HSV but 98-99% specific.[16] If initial HSV PCR is negative and HSV meningitis is suspected, a repeat lumbar puncture 5-7 days later may be useful. Blood in the CSF can also lead to false-negative results.

As PCR becomes more widely available, recognition of enteroviral infections has increased.[12] Additionally, PCR for human parechovirus-3 is becoming more widely available.

Rapid screening is available with latex particle agglutination (LGA) testing of urine, which can be performed for GBS, E coli, and Streptococcus pneumoniae. Unfortunately, the presence of GBS antigen does not prove invasive disease.

If vesicles are present on the skin, evaluation for HSV infection should include cultures of fluid from these vesicles. Swabs of the nasopharynx, conjunctiva, and rectum have also been used to identify viral agents. DNA from HSV or enteroviruses can be identified from either vesicles or CSF by using PCR.

It should be kept in mind that interpretation of CSF findings is more difficult in neonates than in older children, especially in premature infants whose more permeable blood-brain barrier causes higher levels of glucose and protein.

The classic finding of decreased CSF glucose, elevated CSF protein, and pleocytosis is seen more with gram-negative meningitis and with late gram-positive meningitis; this combination also is suggestive of viral meningitis, especially HSV. Only if all 3 parameters are normal does the lumbar puncture provide evidence against infection; no single CSF parameter exists that can reliably exclude the presence of meningitis in a neonate.[30]

The number of white blood cells (WBCs) found in the CSF in healthy neonates varies according to gestational age. Many authors use a cutoff value of 20-30/µL. Bacterial meningitis commonly causes CSF pleocytosis greater than 100/µL, with predominantly polymorphonuclear leukocytes (PMNs) gradually evolving to lymphocytes. In neonates with viral meningitis, the picture may be similar but with a less dramatic pleocytosis. HSV meningitis may be particularly associated with a large number of red blood cells (RBCs) in the CSF.

If the mother is symptomatic, maternal investigation may be warranted; bacterial or viral cultures can provide valuable adjunctive information.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is the neuroimaging modality of choice for identifying focal areas of infection, infarction, secondary hemorrhage, cerebral edema, hydrocephalus, or, rarely, abscess formation. It should be considered in the context of focal neurological abnormalities, persistent infection, or clinical deterioration. Sinovenous occlusions, ventriculitis, and subdural collections are best diagnosed with MRI.

Follow-up MRI scans are useful for following the resolution of the infection, as well as for contributing to prognostication. If available, magnetic resonance spectroscopy can add important information on the metabolic function of the neonatal brain.

Several studies have documented periventricular white matter abnormalities on MRI in infants with neonatal meningitis.[31] Newer MRI technologies, including diffusion-weighted and diffusion tensor imaging, have allowed this association to be evaluated in more detail, and such evaluation may prove to have prognostic implications.[32]

Other Imaging Modalities

Although computed tomography (CT) carries the risk of exposing the neonatal brain to radiation, the rapidity and ease with which it can be obtained (in comparison with MRI) makes it useful in decision-making for potential neurosurgical interventions, such as ventriculostomy for hydrocephalus or surgical drainage of empyema or abscess. It may be particularly appropriate for a critically ill neonate being considered for neurosurgery.

Cranial ultrasonography provides an alternative imaging modality for critically ill neonates, but it does not provide optimal detail in all circumstances. However, it is a low-risk and thus is useful in monitoring ventricular size for hydrocephalus during the acute phase of meningitis.

Chest radiography provides important information about the lung parenchyma and the cardiac silhouette. Meningitis or sepsis may occur with pneumonia but may be indistinguishable from surfactant deficiency, pulmonary hypertension, and obstructive cardiac disease.

Electroencephalography

Electroencephalography (EEG) is not an essential part of the initial diagnostic process. However, in neonates who are unresponsive or have seizures presenting as episodes of apnea, bradycardia, or rhythmic focal movements, EEG monitoring provides useful information to guide treatment with anticonvulsant drugs.

EEG also has some prognostic utility. In a study by Klinger et al, infants with normal or mildly abnormal EEGs had better outcomes, whereas those with moderately-to-markedly abnormal EEGs were more likely to die or to suffer adverse outcomes.[33] In a study by Poblano et al, EEG was predictive of microcephaly and spasticity at 9-month follow-up.[34]

Lumbar Puncture

Lumbar puncture is indicated for evaluation of the CSF in all neonates suspected of having sepsis or meningitis, even in the absence of neurological signs.

Many clinicians are reluctant to perform this procedure on a critically ill infant. Although the theoretical complications of lumbar puncture include trauma, brain-stem herniation, introduction of infection, and hypoxic stress, none of these complications were reported in a meta-analysis of more than 10,000 infants who underwent lumbar puncture.[29]

Meningitis, however, increases the risk of death in neonates. Stoll et al reported a mortality of 23% in babies with CSF-proven meningitis, compared with a mortality of 9% in neonates whose lumbar puncture results were not consistent with meningitis.[35] Additionally, many infants who had negative blood cultures had positive CSF cultures, suggesting that cases of meningitis may be missed.

In cases of bacterial meningitis, repeat lumbar puncture should be performed 24-48 hours after initiation of therapy to ensure sterilization of the CSF. After a full course of therapy for PCR-proven HSV, repeat lumbar puncture should be undertaken to rule out incompletely treated infections.

Pharmacologic and Supportive Therapy

Although evaluation and treatment of perinatal infection often begins before birth, discussion of antenatal interventions is beyond the scope of this review. However, early initiation of antimicrobial drugs is essential; a confirmed diagnosis of meningitis seldom is established before treatment is started.

Aggressive antimicrobial intervention is lifesaving in neonates with suspected meningitis. Because distinguishing viral from bacterial meningitis is difficult early in the clinical course, a combination of agents is often necessary, providing coverage for both types of infection. The duration of therapy for bacterial and herpes simplex virus (HSV) meningitis with an appropriate agent is typically 14-21 days.

Although there is a consensus that acyclovir is the preferred antiviral therapy, there remains some disagreement with respect to what constitutes optimal antibacterial therapy. The combination of ampicillin and gentamicin is a common regimen. Resistance of E coli to ampicillin has been reported; this may be related to increased use of intrapartum antibiotic prophylaxis.[36]

In treating meningitis, many centers administer cefotaxime in addition to or instead of gentamicin, particularly when gram-negative infections are suspected. Cefotaxime is also often used rather than gentamicin when there are concerns regarding renal function, given the potential nephrotoxicity of the latter. However, the use of cefotaxime has been linked to the emergence of cephalosporin-resistant strains of several gram-negative species.[37] Antimicrobial resistance may be even more problematic in developing countries; resistance of E coli and Klebsiella species to ampicillin, gentamicin, and cephalosporins is on the rise.[38]

The choice of an antibiotic regimen should be based on the likely pathogen, the local patterns of antibacterial drug sensitivities, and the policies of the hospital.

Corticosteroids have been shown to reduce long-term sequelae, particularly hearing loss, in older infants with Haemophilus influenzae type B meningitis and S pneumoniae infection. However, use of corticosteroids is not recommended for neonates with meningitis.[39]

Supportive care is focused on supporting blood pressure to maintain adequate cerebral perfusion and preventing secondary brain injury. Meticulous fluid management is important to minimize cerebral edema and to respond to inappropriate antidiuretic hormone (ADH) secretion. The syndrome of inappropriate ADH secretion (SIADH) may cause hyponatremia and hypo-osmolality, which may increase lethargy and seizures while further increasing intracranial pressure (ICP).

Management of seizures is a common challenge in neonates with meningitis. Phenobarbital and phenytoin remain the current drugs of choice, with benzodiazepines utilized as adjunctive therapy. Respiratory dysfunction, disseminated intravascular coagulation (DIC), and nutritional deficiencies should be managed by experienced neonatologists.

Assessment of response to therapy

Lumbar puncture, especially for cerebrospinal fluid (CSF) culture and sensitivity, should be repeated 24-48 hours after the initial study to monitor the course of the infection and guide further treatment decisions. If the patient has persistent infection in the lumbar CSF or clinical deterioration that is not explained by other complications, imaging studies to investigate for abscess formation should be performed. A diagnostic tap of the lateral ventricle should be considered to assess for ventriculitis if no focal abscess is noted on imaging. Ventriculitis may occur, especially with gram-negative bacteria, in the absence of pleocytosis in the lumbar CSF or with sterile CSF.

Given the high sensitivity and specificity of polymerase chain reaction (PCR) assay for HSV, a negative HSV-PCR result in the initial CSF sample is an acceptable end point for discontinuance of empiric acyclovir treatment. However, if any clinical data continue to suggest HSV, consider a full course of treatment despite the negative HSV-PCR result. At some centers, lumbar puncture is repeated 3 weeks after completion of therapy for PCR-proven HSV meningitis to confirm that the virus has been eradicated.

Infants with partially treated bacterial meningitis should be managed on a case-by-case basis in accordance with their clinical presentation. These infants should be observed for at least 48 hours after treatment is discontinued.

C-reactive protein levels can be useful in identifying the presence of a systemic anti-inflammatory response and can be used serially to track the response to treatment.

Ventriculostomy

Ventriculostomy with external drainage may be required in cases where acute hydrocephalus develops secondary to obstruction of CSF flow.

Administration of intraventricular antibiotics is recommended in cases of ventriculitis, but is no longer recommended as a routine treatment for gram-negative meningitis.

Prevention

The use of intrapartum antibiotic prophylaxis in pregnant mothers who are positive for group B streptococcal (GBS) colonization on screening or have risk factors for GBS colonization has reduced the incidence of neonatal early-onset GBS meningitis from approximately 1.8 cases to 0.3 cases per 1000 live births.[9] Screening and risk factor assessment should be included universally in routine prenatal care.

Cesarean delivery decreases, but does not eliminate, transmission of HSV from the mother’s genital tract to the neonate in cases of known infection. Suppressive antiviral therapy for HSV-infected women during the third trimester may prevent recurrent infectious episodes and thereby minimize the infant’s exposure to the virus during delivery.[16]

Long-Term Monitoring

Because of the potential for hearing loss, neonates with meningitis should undergo brainstem auditory evoked response (BAER) testing at 4-6 weeks after discharge.[40] Survivors of neonatal meningitis require long-term surveillance not only for disorders of hearing but also for disorders of vision, motor, or cognitive function.

Developmental delay is a frequent complication of neonatal meningitis. Early intervention services should be employed to maximize developmental gains.

Medical Care

Recommendations for specific microbial therapy based on isolated pathogen and susceptibility testing[46]

Recommended dosages of antimicrobial therapy based on age 

Surgical Care

In the event that these complications manifest after antibiotic therapy, neurosurgical intervention may be required for the aggressive treatment during the acute stage of bacterial meningitis. Patients with these complications are assessed by neuroimaging (CT scan, MRI, cranial ultrasonography) to confirm lesions and the need for neurosurgery.[44]

Clinical features assessed prior to surgical intervention:

Complications

Despite advances in antimicrobial therapy, mortality and morbidity remains high in neonatal meningitis. In infants that have unsatisfactory responses to antibiotic treatment, there are a number of complicated manifestations that arise.

Clinical presentation of complications includes[44] : 

In addition to neurologic complications, cerebrovascular complications also occur with infantile bacterial meningitis. With the development of cerebrovascular complications, there is an onset of mechanisms that are involved.

Detrimental mechanisms that contribute to cerebrovascular complications include[45] :

The sequela of cerebrovascular complications often leads to cerebral infarction. This further leads to cerebral ischemia, seizures, hydrocephalus, and other complications of pathogeneses. 

Diet

Listeria monocytogenes and Escherichia coli are bacteria found in contaminated foods that can cause neonatal meningitis.[43] By avoiding certain foods and safely preparing produce, pregnant mothers can reduce the risk of neonatal meningitis caused by these bacteria.

Foods to avoid that may be contaminated by listeria include:

Foods that must be safely prepared to prevent the growth of listeria and E. coli include:

Medication Summary

Aggressive antimicrobial intervention is lifesaving in neonates with suspected meningitis. Because distinguishing viral from bacterial meningitis is difficult early in the clinical course, a combination of agents is often necessary, providing coverage for both types of infection.

In most institutions, acyclovir is the preferred antiviral therapy, but the best antibacterial therapy remains subject to debate. The combination of ampicillin and gentamicin is a common regimen. Many centers use cefotaxime in addition to or instead of gentamicin, particularly when gram-negative infections are suspected. Selection of antibiotics should be based on likely pathogens, local patterns of antibacterial drug sensitivities, and hospital policies.

In addition to the medications listed below, pleconaril is an experimental agent that interferes with attachment, entry, and uncoating of enteroviruses. It was shown to be well tolerated by neonates in a single, small, double-blinded study. Data supporting the efficacy of pleconaril are limited, although a larger clinical trial is currently under way. At present, this drug is available only for compassionate use or in clinical trials.

Acyclovir (Zovirax)

Clinical Context:  Acyclovir is the preferred treatment for herpes simplex virus (HSV) meningitis. Intravenous (IV) therapy is treatment of choice for neonatal HSV infection, regardless of clinical presentation. Acyclovir is activated by herpes-specific thymidine kinase; it prevents viral replication by inhibiting viral DNA polymerase. Because it is excreted primarily by the kidneys, dosing must be modified in patients with renal impairment.

Class Summary

Antiviral agents inhibit viral replication and activity.

Ampicillin

Clinical Context:  Ampicillin has bactericidal activity against susceptible organisms. The combination of ampicillin with an aminoglycoside is the initial treatment of choice for neonates with presumptive group B streptococcal (GBS) meningitis and for most other suspected bacterial infections of the central nervous system (CNS).

Penicillin G (Pfizerpen)

Clinical Context:  Penicillin G interferes with synthesis of cell-wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. It can be given alone to treat GBS meningitis when susceptibility of CSF isolates to the drug has been demonstrated.

Cefotaxime (Claforan)

Clinical Context:  Cefotaxime is a third-generation cephalosporin with a gram-negative spectrum of activity; it has lower efficacy against gram-positive organisms. It arrests bacterial cell-wall synthesis, which, in turn, inhibits bacterial growth.

Whereas ampicillin plus an aminoglycoside remains the initial treatment of choice for bacterial meningitis, some investigators recommend ampicillin plus a cephalosporin (eg, cefotaxime) as initial treatment. The rapid emergence of cephalosporin-resistant strains limits the use of the latter combination, unless gram-negative bacterial meningitis strongly suspected. Treatment typically lasts 21 days, with most authorities recommending 14-21 days from the first negative CSF culture.

Gentamicin

Clinical Context:  Gentamicin is the prototypical aminoglycoside for combining with ampicillin to treat neonatal meningitis, but organism sensitivities and hospital protocols vary widely. Evolving bacterial resistance may necessitate the use of higher doses.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Either gram-positive or gram-negative organisms may cause bacterial sepsis and meningitis. Combination therapy is necessary.

Phenobarbital

Clinical Context:  Phenobarbital increases the activity of gamma-aminobutyric acid, an inhibitory neurotransmitter in the central nervous system. This medication is typically used as the first-line agent in the treatment of neonatal seizures. An IV dose may require approximately 15 minutes to attain peak levels in the brain. Typically, a loading dose of 20 mg/kg IV is given initially, with additional bolus doses of 5-10 mg/kg if seizure activity persists, to a maximum total dose of 40 mg/kg.

Fosphenytoin (Cerebyx)

Clinical Context:  Fosphenytoin is the diphosphate ester salt of phenytoin and acts as a water-soluble prodrug of that agent. After administration, plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin. Phenytoin, in turn, stabilizes neuronal membranes and decreases seizure activity.

To eliminate the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses, express the dose in terms of phenytoin sodium equivalents (PE). Although fosphenytoin can be administered either IV or IM, IV administration is preferable and should be used in emergency situations.

Fosphenytoin is typically considered the second choice of anticonvulsants in neonates if phenobarbital does not control seizures.

Lorazepam (Ativan)

Clinical Context:  Lorazepam is a benzodiazepine anticonvulsant that is used in cases that are refractory to phenobarbital and phenytoin. By increasing the action of gamma-aminobutyric acid (GABA) the major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the CNS, including the limbic system and the reticular formation.

Class Summary

Anticonvulsants prevent seizure recurrence and terminate clinical and electrical seizure activity.

Author

Gaurav Gupta, MD, Assistant Professor, Section Head, Endovascular and Cerebrovascular Neurosurgery, Fellowship Director, Endovascular Neurosurgery Fellowship (Site), Department of Surgery, Division of Neurosurgery, Rutgers Robert Wood Johnson Medical School

Disclosure: Nothing to disclose.

Coauthor(s)

Fawaz Al-Mufti, MD, Assistant Professor of Neurology, Neurosurgery, and Radiology, Rutgers Robert Wood Johnson Medical School; Attending Physician in Neuroendovascular Surgery and Neurocritical Care, Rutgers Robert Wood Johnson University Hospital

Disclosure: Nothing to disclose.

Love Roa, BS, Medical Scribe, Department of Cardiology, Englewood Hospital

Disclosure: Nothing to disclose.

Sudipta Roychowdhury, MD, Clinical Associate Professor of Radiology, Department of Radiology, Rutgers Robert Wood Johnson Medical School; Attending Radiologist/Neuroradiologist, University Radiology Group, PC

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Attending Neurologist, Children's National Medical Center

Disclosure: Have stock (managed by a financial services company) in healthcare companies including Allergan, Cellectar Biosciences, CVS Health, Danaher Corp, Johnson & Johnson.

Additional Contributors

David C Dredge, MD, Attending Physician, Pediatric Neurology, Baystate Children's Hospital; Assistant Professor of Pediatrics, Tufts University Medical School

Disclosure: Nothing to disclose.

Kalpathy S Krishnamoorthy, MD, Associate Professor of Pediatrics and Neurology, Harvard Medical School; Consulting Staff, Division of Pediatric Neurology, Massachusetts General Hospital

Disclosure: Nothing to disclose.

Acknowledgements

Sarah M Barnett, MD, MPH Fellow in Neonatal Neurology, Division of Pediatric Neurology, Massachusetts General Hospital

Sarah M Barnett, MD, MPH is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Public Health Association, Child Neurology Society , and Massachusetts Medical Society

Disclosure: Nothing to disclose.

David A Griesemer, MD Professor, Departments of Neuroscience and Pediatrics, Medical University of South Carolina

David A Griesemer, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology , American Epilepsy Society, Child Neurology Society, and Society for Neuroscience

Disclosure: Nothing to disclose.

J Stephen Huff, MD Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine

J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References

  1. Volpe JJ. Bacterial and fungal intracranial infections. Neurology of the Newborn. 5th. Philadelphia, Pa: Saunders Elsevier; 2008. 916-56.
  2. Volpe JJ. Viral, protozoal, and related intracranial infections. Neurology of the Newborn. 5th. Philadelphia, Pa: Saunders Elsevier; 2008. 851-915.
  3. Krebs VLJ, Costa GAM. Clinical outcome of neonatal bacterial meningitis according to birth weight. Arq. December 2007. 65:1149-1153. [View Abstract]
  4. Davies PA, Rudd PT. Incidence; The Developing Brain. Neonatal Meningitis. Cambridge, England: Cambridge University Press; 1994. Ch 1.
  5. Klinger G, Chin CN, Beyene J, et al. Predicting the outcome of neonatal bacterial meningitis. Pediatrics. 2000 Sep. 106(3):477-82. [View Abstract]
  6. Heath PT, Nik Yusoff NK, Baker CJ. Neonatal meningitis. Arch Dis Child Fetal Neonatal Ed. 2003 May. 88(3):F173-8. [View Abstract]
  7. Tiskumara R, Fakharee SH, Liu C-Q, Nuntnarumit P, Lui K-M, Hammoud M, et al. Neonatal infections in Asia. Arch Dis Child Fetal Neonatal Ed. March 2009. 94:F144-8. [View Abstract]
  8. Zaidi AK, Thaver D, Ali SA, Khan TA. Pathogens associated with sepsis in newborns and young infants in developing countries. Pediatr Infect Dis J. 2009 Jan. 28(1 Suppl):S10-8. [View Abstract]
  9. Puopolo KM, Madoff LC, Eichenwald EC. Early-onset group B streptococcal disease in the era of maternal screening. Pediatrics. 2005 May. 115(5):1240-6. [View Abstract]
  10. CDC. Trends in perinatal group B streptococcal disease - United States 2000-2006. Morb Mortal Wkly Rep. February 2009. 58:109-112. [View Abstract]
  11. CDC. Enterovirus surveillance--United States, 2002-2004. MMWR Morb Mortal Wkly Rep. 2006 Feb 17. 55(6):153-6. [View Abstract]
  12. Tebruegge M, Curtis N. Enterovirus infections in neonates. Semin Fetal Neonatal Med. March 2009. 1-6. [View Abstract]
  13. Levorson RE, Jantausch BA, Wiedermann BL, Spiegel HM, Campos JM. Human parechovirus-3 infection: emerging pathogen in neonatal sepsis. Pediatr Infect Dis J. 2009 Jun. 28(6):545-7. [View Abstract]
  14. Selvarangan R, Nzabi M, Selvaraju SB, Ketter P, Carpenter C, Harrison CJ. Human parechovirus 3 causing sepsis-like illness in children from midwestern United States. Pediatr Infect Dis J. 2011 Mar. 30(3):238-42. [View Abstract]
  15. Hunter JH, Petrosyan M, Ford HR, Prasadarao NV. Enterobacter sakazakii: An emerging pathogen in infants and neonates. Surg Infect (Larchmt). October 2008. 9:533-539.
  16. Kimberlin D. Herpes simplex virus, meningitis, and encephalitis in neonates. Herpes. 2004. 11 Supp 2:65A-76A. [View Abstract]
  17. Thaver D, Zaidi AK. Burden of neonatal infections in developing countries: a review of evidence from community-based studies. Pediatr Infect Dis J. 2009 Jan. 28(1 Suppl):S3-9. [View Abstract]
  18. de Louvois J, Halket S, Harvey D. Effect of meningitis in infancy on school-leaving examination results. Arch Dis Child. 2007 Nov. 92(11):959-62. [View Abstract]
  19. Chang CJ, Chang HW, Chang WN, Huang LT, Huang SC, CHang YC. Seizures complicating infantile and childhood bacterial meningitis. Pediatr Neurol. September 2004. 32:165-171. [View Abstract]
  20. Stevens JP, Eames M, Kent A, et al. Long term outcome of neonatal meningitis. Arch Dis Child Fetal Neonatal Ed. 2003. 88:F179-184. [View Abstract]
  21. Bedford H, de Louvois J, Halket S, et al. Meningitis in infancy in England and Wales: follow up at age 5 years. BMJ. 2001 Sep 8. 323(7312):533-6. [View Abstract]
  22. Pong A, Bradley JS. Bacterial meningitis and the newborn infant. Infect Dis Clin North Am. 1999 Sep. 13(3):711-33, viii. [View Abstract]
  23. Unhanand M, Mustafa MM, McCracken Gh, Nelson JD. Gram-negative enteric bacillary meningitis: a twenty-one year experience. J Pediatr. January 1993. 122:15-21. [View Abstract]
  24. Miyairi I, Causey KT, DeVincenzo JP, Buckingham SC. Group B streptococcal ventriculitis: a report of three cases and literature review. Pediatr Neurol. May 2006. 34:395-399. [View Abstract]
  25. Ment LR, Ehrenkranz RA, Duncan CC. Bacterial meningitis as an etiology of perinatal cerebral infarction. Pediatr Neurol. September/October 1986. 2:276-279. [View Abstract]
  26. Fitzgerald KC, Golomb MR. Neonatal arterial ischemic stroke and sinovenous thrombosis associated with meningitis. J Child Neurol. July 2007. 22:818-822. [View Abstract]
  27. Bao X, Wong V. Brainstem auditory-evoked potential evaluation in children with meningitis. Pediatr Neurol. 1998 Aug. 19(2):109-12. [View Abstract]
  28. Committee on Medical Liability, American Academy of Pediatrics. Berger JE ed, Deitschel CH Jr ed. Medical Liability for Pediatricians. 6th ed. 2004. 163, 169.
  29. Malbon K, Mohan R, Nicholl R. Should a neonate with possible late onset infection always have a lumbar puncture?. Arch Dis Child. 2006 Jan. 91(1):75-6. [View Abstract]
  30. Garges HP, Moody MA, Cotten CM, et al. Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters?. Pediatrics. 2006 Apr. 117(4):1094-100. [View Abstract]
  31. Shah DK, Daley AJ, Hunt RW, Volpe JJ, Inder TE. Cerebral white matter injury in the newborn following Escherichia coli meningitis. Eur J Paediatr Neurol. 2005. 9:13-17. [View Abstract]
  32. Malik GK, Trivedi R, Gupta A, Singh R, Prasad KN, Gupta RK. Quantitative DTI assessment of periventricular white matter changes in neonatal meningitis. Brain Dev. May 2008. 30:334-341. [View Abstract]
  33. Klinger G, Chin CN, Otsubo H, et al. Prognostic value of EEG in neonatal bacterial meningitis. Pediatr Neurol. 2001 Jan. 24(1):28-31. [View Abstract]
  34. Poblano A, Gutierrez R. Correlation between the neonatal EEG and the neurological examination in the first year of life in infants with bacterial meningitis. Arq Neuropsiquiatr. September 2007. 65:576-580. [View Abstract]
  35. Stoll BJ, Hansen N, Fanaroff AA, et al. To tap or not to tap: high likelihood of meningitis without infection in very low birthweight infants. Pediatrics. 2004. 113:1181-6. [View Abstract]
  36. Alarcon A, Pena P, Salas S, Sancha M, Omenaca F. Neonatal early onset Escherichia coli sepsis: trends in incidence and antimicrobial resistence in the era of intrapartum antimicrobial prophylaxis. Pediatr Infect Dis J. April 2004. 23:295-299. [View Abstract]
  37. Pickering LD, ed. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, Ill: American Academy of Pediatrics; 2006.
  38. Thaver D, Ali SA, Zaidi AK. Antimicrobial resistance among neonatal pathogens in developing countries. Pediatr Infect Dis J. 2009 Jan. 28(1 Suppl):S19-21. [View Abstract]
  39. Chaudhuri A. Adjunctive dexamethasone treatment in acute bacterial meningitis. Lancet Neurol. 2004 Jan. 3(1):54-62. [View Abstract]
  40. Wellman MB, Sommer DD, McKenna J. Sensorineural hearing loss in postmeningitic children. Otol Neurotol. 2003 Nov. 24(6):907-12. [View Abstract]
  41. Ku LC, Boggess KA, Cohen-Wolkowiez M. Bacterial Meningitis in the Infant. Clinics in perinatology. 2014 Dec 6. 42(1):29-45.
  42. Heath PT, Okike IO, Oeser C. Neonatal meningitis: can we do better?. Adv Exp Med Biol. 22 Sept 2011. 719:11-24.
  43. Centers for Disease Control and Prevention. Listeria (Listeriosis) Prevention. CDC. 12 Dec 2016.
  44. Ying-Chao Chang, MD, Chao-Ching Huang, MD, Shan-Tair Wang, PhD, et al. Risk Factor of Complications Requiring Neurosurgical Intervention in Infants With Bacterial Meningitis. Pediatric Neurology. 1997. 17:144-149.
  45. Chin-Jung Chang, Wen-Neng Chang, Li-Tung Huang, Song-Chei Huang, Ying-Chao Chang, Pi-Lien Hung, et al. Bacterial meningitis in infants: the epidemiology, clinical features, and prognostic factors. Brain and Development. April 2004. 26:168-175.
  46. [Guideline] Allan R. Tunkel, Barry J. Hartman, Sheldon L. Kaplan, Bruce A. Kaufman, Karen L. Roos, Michael Scheld, et al. Practice Guidelines for Bacterial Meningitis. Clinical Infectious Diseases. November 2004. 39:1267-1284.

Acute bacterial meningitis (same patient as in the other two images). This axial nonenhanced CT scan shows mild ventriculomegaly and sulcal effacement.

Acute bacterial meningitis (same patient as in the other two images). This axial T2-weighted MRI shows only mild ventriculomegaly

Acute bacterial meningitis (same patient as in the other two images). This contrast-enhanced, axial T1-weighted MRI shows leptomeningeal enhancement (arrows).

Meninges of the central nervous parts

Neisseria meningitidis

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.

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

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.

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

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.