Detectability of Early Brain Meningitis with Magnetic Resonance Imaging

Runge, Val M.; Wells, John W.; Williams, Neil M.; Lee, Charles; Timoney, John F.; Young, Ari

doi:10.1097/00004424-199508000-00006

Cited by 35 publications

(34 citation statements)

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“…Pneumococcal meningitis produced only little opening of the BBB as demonstrated by electron microscopy of brain capillary endothelial tight junctions and measurement of Evans blue dye extravasation, suggesting little vasogenic brain edema. This agrees with the observation that in humans (40), dogs (41), and rats (42) non-complicated bacterial meningitis does not on magnetic resonance scans cause parenchymal enhancement (which would suggest disruption of the BBB), but only meningeal enhancement.…”

Section: Discussionsupporting

confidence: 91%

Aquaporin-4 Gene Disruption in Mice Reduces Brain Swelling and Mortality in Pneumococcal Meningitis

Papadopoulos

Verkman

2005

Journal of Biological Chemistry

276

193

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The astroglial water channel aquaporin-4 (AQP4) facilitates water movement into and out of brain parenchyma. To investigate the role of AQP4 in meningitisinduced brain edema, Streptococcus pneumoniae was injected into cerebrospinal fluid (CSF) in wild type and AQP4 null mice. AQP4-deficient mice had remarkably lower intracranial pressure (9 ؎ 1 versus 25 ؎ 5 cm H 2 O) and brain water accumulation (2 ؎ 1 versus 9 ؎ 1 l) at 30 h, and improved survival (80 versus 0% survival) at 60 h, through comparable CSF bacterial and white cell counts. Meningitis produced marked astrocyte foot process swelling in wild type but not AQP4 null mice, and slowed diffusion of an inert macromolecule in brain extracellular space. AQP4 protein was strongly up-regulated in meningitis, resulting in a ϳ5-fold higher water permeability (P f ) across the blood-brain barrier compared with non-infected wild type mice. Mathematical modeling using measured P f and CSF dynamics accurately simulated the elevated lower intracranial pressure and brain water produced by meningitis and predicted a beneficial effect of prevention of AQP4 upregulation. Our findings provide a novel molecular mechanism for the pathogenesis of brain edema in acute bacterial meningitis, and suggest that inhibition of AQP4 function or up-regulation may dramatically improve clinical outcome.Streptococcus pneumoniae (pneumococcus) is the most common and aggressive meningeal pathogen (1-3). The overall incidence of pneumococcal meningitis is rising (4, 5) and the emergence of penicillin-resistant S. pneumoniae makes treatment harder (6, 7). Even with effective antibiotic treatment, mortality from pneumococcal meningitis is 10 -30%, with 30 -50% of patients acquiring permanent neurological deficits (1-3). A major complication associated with unfavorable outcome in bacterial meningitis is brain edema, which causes a rise in intracranial pressure potentially leading to brain ischemia, herniation, and death (8, 9). The molecular mechanisms responsible for the formation and absorption of excess fluid in brain edema associated with meningitis are poorly understood.The two main types of brain edema are cytotoxic and vasogenic (10). Cytotoxic edema, as occurs in ischemic stroke, refers to cell swelling that primarily affects astroglial cells. Vasogenic edema, as occurs in brain tumors, involves accumulation of excess fluid in the extracellular space of the brain parenchyma because of a leaky blood-brain barrier (BBB). 1 Although both types of brain edema are thought to co-exist in meningitis (8, 9), their relative contributions to brain swelling are not known.Recently, the bidirectional water channel aquaporin-4 (AQP4) has been found to play an important role in brain-water homeostasis (11-16). AQP4 protein is expressed strongly in astroglia at the BBB and CSF-brain interfaces (17, 18), suggesting involvement in water movement between fluid compartments (blood and CSF) and brain parenchyma. AQP4 deletion markedly reduced brain swelling in mouse models of cytotoxic brain edema, includin...

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Section: Discussionsupporting

confidence: 91%

Aquaporin-4 Gene Disruption in Mice Reduces Brain Swelling and Mortality in Pneumococcal Meningitis

Papadopoulos

Verkman

2005

Journal of Biological Chemistry

276

193

View full text Add to dashboard Cite

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“…25 Contrast enhancement is influenced by contrast dose, imaging technique, and time gap between contrast administration and imaging. 12 Our observations of increased FA values in the enhanced as well as nonenhanced cerebral cortical regions on postcontrast T1-weighted images in patients with meningitis suggest more diffuse inflammatory activities.…”

Section: Discussionmentioning

confidence: 59%

“…However, not all active meningeal infections demonstrate enhancement on MRI after administration of standard dose of gadolinium chelate. 12 It has been demonstrated that the detection of abnormal meningeal enhancement on conventional T1-weighted images significantly increases with the use of a higher dose of contrast agent and/or concurrent use of magnetization transfer imaging. 10Y12 There is a threshold of inflammation below which there is not sufficient disruption of blood-meningeal barrier to permit visualization of the abnormality on contrast-enhanced MRI.…”

Section: Discussionmentioning

confidence: 99%

Clinical Implications of Increased Fractional Anisotropy in Meningitis Associated With Brain Abscess

Nath¹,

Husain²,

Trivedi³

et al. 2007

Journal of Computer Assisted Tomography

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“…Contrast-enhanced MRI may result in visualization of abnormal meninges ( Fig. 1) [16]. Diffusionweighted imaging may increase the usefulness of MRI [17].…”

Section: Laboratory Testingmentioning

confidence: 99%

Bacterial meningitis: Diagnosis and treatment

Snyder

2003

Curr Neurol Neurosci Rep

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Bacterial meningitis, once almost universally fatal, remains a cause of serious neurologic illness and subsequent disability. The initial diagnosis, although sometimes clear-cut, can be subtle and difficult. Appropriate intervention may have a favorable influence on outcome. The advent of corticosteroids and brain imaging has improved management but created controversy concerning the sequence at which various interventions should be introduced. Empiric treatment with antibiotics is important in the initial stages. Complications can arise, such as seizures, increased intracranial pressure, and ischemia. The prognosis remains unfavorable for some affected individuals in spite of advances in antibiotic management and supportive care.

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Detectability of Early Brain Meningitis with Magnetic Resonance Imaging

Cited by 35 publications

References 0 publications

Aquaporin-4 Gene Disruption in Mice Reduces Brain Swelling and Mortality in Pneumococcal Meningitis

Aquaporin-4 Gene Disruption in Mice Reduces Brain Swelling and Mortality in Pneumococcal Meningitis

Clinical Implications of Increased Fractional Anisotropy in Meningitis Associated With Brain Abscess

Bacterial meningitis: Diagnosis and treatment

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