eMedicine Specialties > Neurology > Neurological Infections

Staphylococcal Meningitis: Differential Diagnoses & Workup

Author: Lawrence A Zumo, MD, Neurologist, Private Practice
Coauthor(s): Francisco de Assis Aquino Gondim, MD, MSc, PhD, Professor Adjunto II, Departments of Physiology and Pharmacology, Neurology Residency Program Director, Faculdade de Medicina, Universidade Federal do Ceará, Brazil; Alan Greenberg, MD, Director, Associate Professor, Department of Internal Medicine, Jersey City Medical Center, Seton Hall University
Contributor Information and Disclosures

Updated: Mar 27, 2007

Differential Diagnoses

Aseptic Meningitis
Haemophilus Meningitis
Tuberculous Meningitis
Viral Encephalitis
Viral Meningitis

Other Problems to Be Considered

Behçet disease
Chemical meningitis (eg, after spinal anesthesia, myelography)
Epstein-Barr virus infections
Fungal meningoencephalitis
Legionnaire disease
Leptospiral meningoencephalitis
Listeria monocytogenes meningoencephalitis
Necrotizing cerebral angiitis
Neoplastic angioendotheliosis
Mycoplasmal pneumonia
Rickettsial encephalitides

Workup

Laboratory Studies

• CBC with differential demonstrates polymorphonuclear leukocytosis with left shift.
• CSF analysis is the diagnostic test of choice for suspected meningitis.
  • CSF lactate dehydrogenase (LDH) appears to be diagnostic and has a prognostic value in bacterial meningitis. Increase in total LDH is observed consistently in bacterial meningitis, mostly due to increases in fractions 4 and 5, which are derived from granulocytes. LDH fractions 1 and 2, derived presumably from brain tissue, are elevated only slightly in bacterial meningitis but rise sharply in patients who develop neurologic sequelae.
  • Leukocyte count in the CSF ranges from 250-100,000/µL. Counts above 50,000 raise the possibility of a brain abscess having ruptured into a ventricle. Neutrophils predominate early in infection, but mononuclear cells (lymphocytes, plasma cells, histiocytes) steadily increase as the infection continues.
  • Protein content is higher than 45 mg/dL in greater than 90% of cases. In most cases, the protein ranges from 100 to 500 mg/dL.
  • Glucose content is usually diminished to below 40 mg/dL or to less than 40% of blood glucose level.
  • Gram stain of CSF sediment permits identification of the causative agent in most cases.
• Other laboratory methods for identification of causative organisms include counterimmunoelectrophoresis (CIE), radioimmunoassay (RIA), latex particle agglutination (LPA), enzyme-linked immunosorbent assay (ELISA), and—most sensitive of all—gene amplification by polymerase chain reaction (PCR).
• Blood cultures should always be obtained. They are positive in 40-60% of patients with Haemophilus influenzae, meningococcal, or pneumococcal meningitis, but data are scarce for staphylococcal meningitis. Blood cultures may provide the only definite clue as to the causative agent if CSF cultures are negative and if more sophisticated diagnostic identification procedures are not readily available.
• Because of earlier antibiotic intervention in patients presenting with signs suggestive of bacterial meningitis, a noted rise occurs in culture-negative CSF and blood cultures in some laboratories. This makes the use of a non–culture-based system to detect and identify the causal agents increasingly important. It is here that the 16S rRNA PCR becomes a valuable molecular tool to aid in the detection on nonculturable etiologic agents of meningitis. With the advent of polyacrylamide gel electrophoresis (PAGE) to separate mixed 16S rRNA amplicons prior to sequencing without the need of cloning, the PCR technique is increasingly being used to augment staphylococci identification.
• 16S rRNA genes exist in all bacteria and accumulate mutations at a slow constant rate over time; therefore, they may be used as "molecular clocks." Highly variable portions of the 16S rRNA sequence provide unique signatures to any bacterium and useful information about relationships between them. These properties provide important aids in microbiologic diagnostics, especially in equivocal cases.
• Complement levels and immunoglobulin levels should be part of the evaluation of every patient with bacterial meningitis.
• Antibody levels should be monitored and pneumococcal and meningococcal vaccines should be given to those with recurrent bacterial meningitis because this is common in those with previous head trauma, skull fracture, or dural CSF leak, as well as those with deficiencies of any of the complement components or hypogammaglobulinemia.

Imaging Studies

• Chest x-rays are important because they may show an abscess or pneumonitis, an important consideration for infants and immunocompromised patients.
• Sinus and skull x-rays may show the presence of cranial osteomyelitis, paranasal sinusitis, or mastoiditis.
• CT scans of the head are usually normal but may reveal nonspecific cerebral edema or show previous neurosurgical interventions. CT scans reveal eroding skull lesions and routes for bacterial invasion (eg, mastoiditis, sinusitis, tumors, sinus wall defects, brain abscess, subdural empyema). In patients with immunosuppression or with focal findings, papilledema, or other signs of increased intracranial pressure, a CT scan of the head must be done before the spinal tap to detect mass lesions that could result in herniation. Those with space-occupying lesions do not undergo lumbar puncture because the withdrawal of CSF removes counterpressure from below, thus increasing the effect of compression from above and exacerbating the brain shift already present. CT scan should be preceded by blood cultures and the initiation of antibiotic therapy.
• MRI with contrast enhancement may demonstrate cortical reactions, including infarctions, hydrocephalus, and meningeal exudates. The role of MRI with contrast T1 and T2 sequences is not well established.
• Transthoracic and transesophageal echocardiograms are helpful for the evaluation of endocarditis. Negative tests do not rule out endocarditis, since neither technique is sensitive enough to detect small vegetations, which may require more than 10 days to develop.

Other Tests

• Lumbar puncture: CSF pressure is elevated consistently (>180 mm H₂ O), but pressures greater than 400 mm H₂ O suggest the potential for herniation.

Histologic Findings

Pia-arachnoiditis with edema and microinfarcts is observed. Polymorphonuclear leukocytes fill the subarachnoid space in severely affected areas and are found predominantly around the leptomeningeal blood vessels in less severe cases. In fulminant meningitis, the inflammatory cells infiltrate the walls of the leptomeningeal veins and produce a venulitis that can lead to venous occlusion and subsequent hemorrhagic infarction of the underlying brain.

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