Histoplasmosis of the nervous system
Jul. 12, 2023
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Neonatal meningitis represents an important clinical challenge for both the child neurologist and the pediatrician. The clinical presentation of meningitis in newborn infants is frequently nonspecific, and spinal fluid abnormalities may be difficult to differentiate from values typically seen in newborn infants. For this reason, meningitis should be suspected in a newborn who develops poor feeding, irritability, fever, or hypothermia; this is frequently, but not invariably, accompanied by a CSF white blood cell count greater than 30 cells/mm3 and a CSF:serum glucose ratio less than 0.5. Seizures may also suggest the presence of meningitis, although clinical seizures in the newborn may be more subtle or atypical than those seen in older children or adults. Empiric antimicrobial therapy includes a combination of ampicillin and a third- or fourth-generation cephalosporin (usually cefotaxime or ceftazidime) (64). Although adjunctive dexamethasone therapy is recommended in children and adults, there is insufficient evidence to date to recommend dexamethasone therapy for neonatal meningitis.
• Neonatal meningitis includes infections occurring within the immediate postpartum period and also infections occurring during the first few weeks of life. The condition is usually divided into cases occurring within 72 hours of delivery (early onset) and cases occurring after 72 hours postpartum (late onset) up until 28 days of age.
• The major causes of neonatal meningitis are Streptococcus agalactiae (Group B streptococci, GBS) and Gram-negative organisms, in particular Escherichia coli.
• The diagnosis of neonatal meningitis is often difficult. Typical signs of meningeal inflammation are frequently absent, and neonates may present with nonspecific irritability. The neonate may be febrile, euthermic, or hypothermic and may be tachypneic, have apneic spells, or be excessively somnolent. Seizures may occur, but may not resemble seizures seen in older children or adults.
• CSF findings in neonatal meningitis may not easily be distinguished from CSF values typically seen in neonates. However, meningitis should be strongly suspected if CSF white blood cell count is greater than 30 cells/mm3 and the CSF:serum glucose ratio is less than 0.5.
• Empiric treatment of neonatal meningitis involves use of a third- or fourth-generation cephalosporin to cover S agalactiae and Gram-negative organisms, plus ampicillin to cover Listeria monocytogenes.
• Aminoglycosides such as gentamicin do not reliably reach therapeutic concentrations in CSF, and intrathecal administration of these agents has not been effective. Intraventricular administration has been found to increase mortality and is contraindicated.
• Intrapartum administration of antibiotics to mothers infected with S agalactiae has proven crucial to preventing meningitis in the newborn infant.
Although the first description of bacterial meningitis was recorded by Gaspard Vieusseux in 1806 (66), meningitis as a condition of neonates was not reported until 1873, and Flensborg, in one of the first reviews of the condition, was able to identify only 131 cases from the world’s literature (17; 70). That neonatal meningitis was an important condition in the newborn period did not become well-recognized until the 1950s (70). The first manuscript devoted to the neuropathology of neonatal bacterial meningitis in neonates was published in 1966 (05).
Current understanding of neonatal meningitis has been achieved through work in three major areas. The first of these has been an understanding of the disease itself: the realization that neonatal meningitis is not rare, that its etiologic organisms and pathogenesis differ from those associated with childhood and adult meningitis, and that its presentation does not usually resemble that seen in older individuals. The second area has been progress in the treatment of neonatal meningitis. Early clinical trials demonstrated that systemic ampicillin and an aminoglycoside still resulted in 50% mortality and long-term morbidity, that addition of intrathecal gentamicin did not improve outcome, and that use of intraventricular gentamicin resulted in increased mortality (42). Predictably effective antibiotic treatment of neonatal Gram-negative meningitis was achieved only following the advent of the third-generation cephalosporins. The third theme, of great importance over the last two decades, has been the realization that the incidence of S agalactiae meningitis can be reduced by peripartum treatment of mothers testing positive for the organism. Despite these advances, however, neonatal meningitis remains a dangerous condition: although mortality has declined to roughly 10%, an adverse outcome will still be found in 20% to 70% of patients (03; 04; 36; 47).
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