Central nervous system infection in the pediatric population.

Infection of the central nervous system is a life-threatening condition in the pediatric population. Almost all agents can cause infection within the central nervous system and the extent of infection ranges from diffuse involvement of the meninges, brain, or the spinal cord to localized involvement presenting as a space-occupying lesion. Modern imaging techniques define the anatomic region infected, the evolution of the disease, and help in better management of these patients. Acute bacterial meningitis remains a major cause of mortality and long-term neurological disability. Fortunately, the incidence of infection after clean craniotomy is < 5%, but it leads to significant morbidity as well as fiscal loss. The most significant causative factor in postcraniotomy infections is postoperative CSF leak. Cerebral abscess related to organic congenital heart disease is one of the leading causes of morbidity and mortality in the pediatric population. The administration of prophylactic antibiotics is indicated for contaminated and clean-contaminated wounds.

Introduction

Infection of the central nervous system is a life-threatening condition, especially in children, that demands immediate attention from the attending physician or surgeon and the clinical pathologist as well as the microbiologist. Almost all agents can cause infection within the central nervous system and the extent of infection ranges from diffuse involvement of the meninges, brain, or the spinal cord to localized involvement presenting as a space-occupying lesion. Epidemiological considerations, appreciation of the presenting clinical syndrome (acute bacterial meningitis, acute aseptic meningitis, chronic meningitis or space-occupying lesions) and cerebrospinal fluid analysis facilitates diagnosis. Modern imaging techniques define the anatomic region that has been infected and the evolution of the disease, help to evaluate the treatment efficacy, and can frequently help to determine extra-central nervous system sources of infection, such as sinusitis or mastoiditis. Acute bacterial meningitis remains a major worldwide cause of mortality and long-term neurological sequelae. Despite the availability of potent newer antibiotics, the mortality rate due to acute bacterial meningitis remains significantly high (16–32%) in India and other developing countries.[1-4]

Bacteriology of Infection and Host Defenses

Almost every infective agent can cause infections within the CNS, although agents vary in their tendency to do so. Infective agents generally gain access to the CNS either by the hematogenous route or by direct extensions. Most agents that can invade the blood stream can be carried to the CNS. The rare exceptions include rabies virus, herpes simplex virus 1, and . In rabies, the virus travels along the peripheral nerves from the site of infection to the CNS. However, in herpes and infections, the inoculation occurs directly through the olfactory bulbs. Bacterial agents commonly cause infection of the CNS in infants and children. By far, the most common presentation of such infection is meningitis. Less often, intracranial abscesses are found in the epidural, subdural, or intracerebral tissues. The incidence of bacterial meningitis is high in the first few months of life and continues to be high until two years of age, after which it declines considerably.[56] Neonates usually derive their colonization from the maternal gastrointestinal or genitourinary tracts. In the first two weeks of life, group B and are the most common infective agents, accounting for approximately 80–85% of all cases.[7] The bulk of the remaining cases are caused by other coliforms such as , and . Group B type-I are still the most frequent cause of bacterial meningitis in infants between three and six weeks of age.[8] A comprehensive age-wise etiology of meningitis is given in the Table 1.[9]

Table 1

Age-wise etiology of meningitis

Fortunately, the central nervous system is well protected against most micro-organisms because of its unique location deep in the body where it is protected by skin, muscle, bone, and tough fibrous tissue. Surgical interventions transcend these barriers and directly expose the CNS to the possibility of microbiological attacks. However, the body executes a complex series of host defenses to reduce the likelihood that such microbiologic contaminations will proceed to frank infection. Whether a bacterial inoculum in a wound will proceed to a frank infection can be predicted by many factors such as the size and virulence of the inoculum and the level of the host defense present.

Imaging in Infection

Imaging is extremely important in the diagnosis and management of intracranial infections. It defines the anatomic region affected: the epidural or subdural spaces, the pia-arachnoid, the cerebral parenchyma, or the ventricles. It also helps to define the evolution of the process, , the transitions from meningitis to cerebritis to abscess formation. The primary imaging techniques for demonstrating the presence of inflammation and their effects are computerized tomography (CT) and magnetic resonance imaging (MRI). The intravenous injection of an iodinated contrast agent is essential in the CT-assisted diagnosis of cerebritis, cerebral abscess, and ventriculitis. Similarly magnetic resonance contrast agents such as gadolinium-DTPA cross the blood brain barrier in areas of cerebritis or abscess.[1011] MRI is superior to CT scans in showing meningeal enhancement from meningitis because of the absence of bony artifacts of adjacent skull bones seen with CT scans. However, evidence of bony erosion or abnormalities due to inflammation is more clearly demarcated in CT scans than in MRI.

Specific CNS Infections

Craniotomy infections

In most hospitals, the incidence of infection after clean craniotomy is < 5%. There are several contributing factors such as the duration of surgery, re-exploration surgery, age of the patient, and postoperative CSF leaks.[1213] However, the most significant causative factor in postcraniotomy infections is the postoperative CSF leak.[14] CSF fistulae offer routes for bacterial entry and should be treated promptly.[12] A few stitches in time when the skin is healthy, solve the problem in most cases. Sometimes, repeated lumber punctures or a spinal drain help and enables the CSF fistula to scar.

Amongst the further complications of craniotomy infections are postoperative meningitis, empyema, abscess formation, wound gap, and bone flap infections. Postoperative meningitis is not very common but it is a potentially lethal complication[15] with sp . being common pathogens in such meningitis. Lumber puncture should be done to exclude meningitis in the postoperative period if the patients show signs of meningismus with fever. Choosing a proper antibiotic is as important as administering these antibiotics in proper doses.[16]

Bone flap infection

The incidence of bone flap infection following craniotomy is greater when the bone is devascularized. Bone flap infections are characterized by a local inflammation and a nonhealing fistula. The standard treatment is removal of the infected bone flap and cranioplasty at a later date.[1718]

CSF shunt infection

CSF shunt infections are one of the most important infections encountered by neurosurgeons. According to several studies, the incidence varies from 5–39% of all shunts[1920] and the infective etiology is responsible for hydrocephalus in a significant number of children (36%).[20] The possibility of TORCH infection as a cause of hydrocephalus should be considered during antenatal check-up even among the children of screened mothers. As colonization of shunt tubing occurs most frequently during surgery, the organisms are usually skin pathogens, especially sp., both coagulase-positive and coagulase-negative types. , (coagulase-negative) makes up the largest group of microorganisms that colonize shunts.[21] There is some controversy about whether antibiotic-impregnated shunts help in preventing infection.[2223] Sometimes, brain abscess and other uncommon complications can occur due to shunt insertion.[2425]

Intracranial Abscess

The incidence of brain abscess is higher in India. Bhatia , reported that abscess comprised 8% of all intracranial spinal space-occupying lesions.[25] Brain abscess is initiated when micro-organisms are introduced as a result of trauma, contiguous infection, or hematogenous dissemination. Sometimes, the abscess confines itself to subdural spaces and is then known as subdural empyema [Figure 1]. The source of infection is frequently found and the cause remains obscure in 10–37% of patients.[26] Suppurative infections of the paranasal sinus, middle ear, and mastoid are the most common sources of underlying infection in most clinical series.[27-29] Metastatic abscesses occur through hematogenous dissemination of micro-organisms from a remote site of infection. Common primary foci include skin pustules, pulmonary infections (empyema, bronchiectasis, abscess and pneumonia), osteomyelitis, dental abscess, and subacute bacterial endocarditis. Metastatic abscesses occur in multiples and tend to occur at the cortico-medullary junction where the blood flow is slowest.[30] Cerebral abscess related to organic congenital heart disease is one of the leading causes of morbidity and mortality in the pediatric population.[31] Tubercular brain abscess (TBA) is a rare manifestation of CNS tuberculosis. It is characterized by an encapsulated collection of pus containing viable tubercular bacilli without any evidence of tubercular granuloma.[32] Britt , divided abscess formation into four stages based on histopathologic data.[33] The early celebrities (days one to three) stage is characterized by the presence of a necrotic center accompanied by a local inflammatory response surrounding the adventitia of blood vessels [Figure 2]. In the late celebrities phase (days four to nine), pus formation occurs leading to the enlargement of the necrotic center, which is surrounded by a zone of inflammatory cells and macrophages; maximum edema occurs during this phase. Early encapsulation phase begins subsequently with capsulation consolidating around the necrotic center. The late capsule phase occurs around 14 days with dense collagen capsulation surrounded by a gliotic pseudocapscule.[33] The treatment of the brain abscess is usually nonsurgical, but surgical aspiration or excision of the whole abscess in necessary in most cases.[34] Occasionally, spontaneous evacuation of intracranial abscesses has been reported through normal or abnormal pathways.[35]

Figure 1

Brain abscess in contrast-enhanced CT scan

Figure 2

Interhemispheric subdural empyema

Neurosurgical Infections in the Immunocompromised Host

Infection involving the CNS is often devastating in patients with compromised immune function. The incidence of CNS infection in immunocompromised patients is 0.6–14% with a mortality rate of 42–77%. Sometimes, intracranial infections harbor unusual organisms such as sp. etc.[36] Meningitis and encephalitis represent most CNS infections in immunocompromised patients and do not usually require neurosurgical attention. The developments of brain abscess in the compromised host signals a neurosurgical emergency. Organ transplantation and cancer patients comprise the majority of immunocompromised patients who are prone to brain abscess formation.[37] The duration of immunosuppressant therapy is a major determining factor for the development of CNS infection. After organ transplantation, the maximal risk of CNS infection for transplants recipients is for the first four months. Potential infections including sp, , and sp are more common. Among fungal infections, sp is common.[3839]

Tubercular abscess formation has been described in some cases.[40]

Antibiotic Prophylaxis in Neurosurgery

Due to a low risk of infection (2–3%), prophylactic use of antibiotics in neurosurgery is a controversial issue. Some neurosurgeons believe that there are strong arguments against the use of antimicrobials (promotion of antibiotic-resistant strains of bacteria, superinfection, and adverse drug reactions) and meticulous aseptic techniques could be more useful than prophylactic antibiotics. On the other hand, despite being rare, the consequences of a neurosurgical infection can be dramatic and may result in rapid death caused by meningitis, cerebritis, abscess formation, or sepsis.[4142] Ideally, a prophylactic antibiotic should achieve high peak tissue concentrations at the site of the wound before the first incision and should be maintained until the time of closure. Currently, the administration of prophylactic antibiotics is indicated for contaminated and clean-contaminated wounds. Clinical studies emphasized that the most important factors influencing the choice of antibiotic prophylaxis in neurosurgery is the patient's immune status, virulence of the pathogens, and the type of surgery (“clean contaminated”--procedure that crosses the cranial sinuses, “clean nonimplant”--procedure that does not cross the cranial sinuses, CSF shunt surgery, skull fracture). Despite the proven effectiveness of antibiotic prophylaxis, many researchers would argue that contemporary dosing regimens should be re-evaluated. The debates concerning the dosage and timing of ideal prophylactic administration are likely to continue.[42]

Discussion

Almost all agents can cause infection within the central nervous system and the extent of infection ranges from diffuse involvement of the meninges, brain, or the spinal cord to localized involvement presenting as a space-occupying lesion. Infection of the central nervous system is a life-threatening condition in the pediatric population. Modern imaging techniques define the anatomic region that has been infected, the evolution of the disease, and help in improved management of these patients. Acute bacterial meningitis remains a major cause of mortality and long-term neurological disability. Fortunately, the incidence of infection after clean craniotomy is < 5%, but it leads to significant morbidity as well as fiscal loss. The most significant causative factor in postcraniotomy infections is the postoperative CSF leak. CSF shunt infection is one of the most important infections encountered by neurosurgeons. (coagulase-negative) makes up the largest group of microorganisms colonizing shunts. Cerebral abscess related to organic congenital heart disease is one of the leading causes of morbility and mortality in the pediatric population. The administration of prophylactic antibiotics is indicated for contaminated and clean-contaminated wounds. The most important factors influencing the choice of antibiotic prophylaxis in neurosurgery are the patient's immune status, the virulence of the pathogens, and the type of surgery performed.