• 1

    Beaver PC, Rosen L, 1945. Memorandum on the first report of Angiostrongylus in man by Nomura and Lin. Am J Trop Med Hyg 13 :589–590.

  • 2

    Rosen L, Chappell R, Laqueur GL, 1962. Eosinophilic meningoencephalitis caused by a metastrongylid lung worm of rats. JAMA 179 :620–624.

    • Search Google Scholar
    • Export Citation
  • 3

    Punyagupta S, Juttijudata P, Bunnag T, 1975. Eosinophilic meningitis in Thailand: clinical studies of 484 typical cases probably caused by Angiostrongylus. Am J Trop Med Hyg 24 :921–931.

    • Search Google Scholar
    • Export Citation
  • 4

    Yii CY, 1976. Clinical observations on eosinophilic meningitis and meningoencephalitis caused by Angiostrongylus cantonensis on Taiwan. Am J Trop Med Hyg 25 :233–249.

    • Search Google Scholar
    • Export Citation
  • 5

    Marshall DW, Brey RL, Cahill WT, Houk RW, Zajac RA, Boswell RN, 1988. Spectrum of cerebrospinal fluid findings in various stages of human immunodeficiency virus infection. Arch Neurol 45 :954–958.

    • Search Google Scholar
    • Export Citation
  • 6

    Lee JD, Tsai LY, Chen CH, Wang JJ, Hsiao JK, Yen CM, 2006. Blood-brain barrier dysfunction occurring in mice infected with Angiostrongylus cantonensis. Acta Trop 97 :204–211.

    • Search Google Scholar
    • Export Citation
  • 7

    van der Flier M, Stockhammer G, Vonk GJ, Nikkels PG, van Diemen-Steenvoorde RA, van der Vlist GJ, Rupert SW, Schmutzhard E, Gunsilius E, Gastl G, Hoepelman AI, Kimpen JL, Geelen SP, 2001. Vascular endothelial growth factor in bacterial meningitis: detection in cerebrospinal fluid and localization in postmortem brain. J Infect Dis 183 :149–153.

    • Search Google Scholar
    • Export Citation
  • 8

    Connolly DT, 1991. Vascular permeability factor: a unique regulator of blood vessel function. J Cell Biochem 47 :219–223.

  • 9

    van Bruggen N, Thibodeaux H, Palmer JT, Lee WP, Fu L, Cairns B, Tumas D, Gerlai R, Williams SP, van Lookeren Campagne M, Ferrara N, 1999. VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain. J Clin Invest 104 :1613–1620.

    • Search Google Scholar
    • Export Citation
  • 10

    van der Flier M, Hoppenreijs S, van Rensburg AJ, Ruyken M, Kolk AH, Springer P, Hoepelman AI, Geelen SP, Kimpen JL, Schoeman JF, 2004. Vascular endothelial growth factor and blood-brain barrier disruption in tuberculous meningitis. Pediatr Infect Dis J 23 :608–613.

    • Search Google Scholar
    • Export Citation
  • 11

    Tsai HC, Lee SS, Huang CK, Yen CM, Chen ER, Liu YC, 2004. Outbreak of eosinophilic meningitis associated with drinking raw vegetable juice in southern Taiwan. Am J Trop Med Hyg 71 :222–226.

    • Search Google Scholar
    • Export Citation
  • 12

    Tsai HC, Liu YC, Kunin CM, Lee SS, Chen YS, Lin HH, Tsai TH, Lin WR, Huang CK, Yen MY, Yen CM, 2001. Eosinophilic meningitis caused by Angiostrongylus cantonensis: report of 17 cases. Am J Med 111 :109–114.

    • Search Google Scholar
    • Export Citation
  • 13

    Tsai HC, Liu YC, Kunin CM, Lai PH, Lee SS, Chen YS, Wann SR, Lin WR, Huang CK, Ger LP, Lin HH, Yen MY, 2003. Eosinophilic meningitis caused by Angiostrongylus cantonensis associated with eating raw snails: correlation of brain magnetic resonance Imaging scans with clinical findings. Am J Trop Med Hyg 68 :281–285.

    • Search Google Scholar
    • Export Citation
  • 14

    Chye SM, Chang JH, Yen CM, 2000. Immunodiagnosis of human eosinophilic meningitis using an antigen of Angiostrongylus cantonensis L5 with molecular weight 204KD. Acta Trop 75 :9–17.

    • Search Google Scholar
    • Export Citation
  • 15

    Bisser S, Lejon V, Preux PM, Bouteille B, Stanghellini A, Jauberteau MO, Buscher P, Dumas M, 2002. Blood–cerebrospinal fluid barrier and intrathecal immunoglobulins compared to field diagnosis of central nervous system involvement in sleeping sickness. J Neurol Sci 193 :127–135.

    • Search Google Scholar
    • Export Citation
  • 16

    Quagliarello V, Scheld WM, 1992. Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med 327 :864–872.

  • 17

    Dorta-Contreras AJ, Reiber H, 1998. Intrathecal synthesis of immunoglobulins in eosinophilic meningoencephalitis due to Angiostrongylus cantonensis. Clin Diagn Lab Immunol 5 :452–455.

    • Search Google Scholar
    • Export Citation
  • 18

    Reiber H, 1994. Flow rate of cerebrospinal fluid (CSF)—a concept common to normal blood–CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci 122 :189–203.

    • Search Google Scholar
    • Export Citation
  • 19

    Marchi N, Fazio V, Cucullo L, Kight K, Masaryk T, Barnett G, Vogelbaum M, Kinter M, Rasmussen P, Mayberg MR, Janigro D, 2003. Serum transthyretin monomer as a possible marker of blood–to–CSF barrier disruption. J Neurosci 23 :1949–1955.

    • Search Google Scholar
    • Export Citation
  • 20

    Proescholdt MA, Heiss JD, Walbridge S, Muhlhauser J, Capogrossi MC, Oldfield EH, Merrill MJ, 1999. Vascular endothelial growth factor (VEGF) modulates vascular permeability and inflammation in rat brain. J Neuropathol Exp Neurol 8 :613–627.

    • Search Google Scholar
    • Export Citation
  • 21

    McIntyre PB, Berkey CS, King SM, Schaad UB, Kilpi T, Kanra GY, Perez CM, 1997. Dexamethasone as adjunctive therapy in bacterial meningitis: a meta-analysis of randomized clinical trials since 1988. JAMA 278 :925–931.

    • Search Google Scholar
    • Export Citation
  • 22

    Heiss JD, Papavassiliou E, Merrill MJ, Nieman L, Knightly JJ, Walbridge S, Edwards NA, Oldfield EH, 1996. Mechanism of dexamethasone suppression of brain tumor–associated vascular permeability in rats: involvement of the glucocorticoid receptor and vascular permeability factor. J Clin Invest 98 :1400–1408.

    • Search Google Scholar
    • Export Citation
  • 23

    Chotmongkol V, Sawanyawisuth K, Thavornpitak Y, 2000. Corticosteroid treatment of eosinophilic meningitis. Clin Infect Dis 31 :660–662.

  • 24

    Sawanyawisuth K, Limpawattana P, Busaracome P, Ninpaitoon B, Chotmongkol V, Intapan PM, Tanawirattananit S, 2004. 1-week course of corticosteroids in the treatment of eosinophilic meningitis. Am J Med 117 :802–803.

    • Search Google Scholar
    • Export Citation
  • 25

    Kaal EC, Vecht CJ, 2004. The management of brain edema in brain tumors. Curr Opin Oncol 16 :593–600.

  • 26

    Kroll RA, Neuwelt EA, 1998. Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and other means. Neurosurgery 42 :1083–1099.

    • Search Google Scholar
    • Export Citation
  • 27

    Berk BC, Corson MA, Peterson TE, Tseng H, 1995. Protein kinases as mediators of fluid shear stress stimulated signal trans-duction in endothelial cells: a hypothesis for calcium-dependent and calcium-independent events activated by flow. J Biomech 28 :1439–1450.

    • Search Google Scholar
    • Export Citation
  • 28

    Dascalu A, Oron Y, Nevo Z, Korenstein R, 1995. Hyperosmotic modulation of the cytosolic calcium concentration in a rat osteoplast-like cell line. J Physiol 486 :97–104.

    • Search Google Scholar
    • Export Citation
  • 29

    Leib SL, Tauber MG, 1999. Pathogenesis of bacterial meningitis. Infect Dis Clin North Am 13 :527–548.

  • 30

    Stockhammer G, Poewe W, Burgstaller S, Deisenhammer F, Muigg A, Kiechl S, Schmutzhard E, Maier H, Felber S, Schumacher P, Gunsilius E, Gastl G, 2000. Vascular endothelial growth factor in CSF: a biological marker for carcinomatous meningitis. Neurology 54 :1670–1676.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

VASCULAR ENDOTHELIAL GROWTH FACTOR IS ASSOCIATED WITH BLOOD BRAIN BARRIER DYSFUNCTION IN EOSINOPHILIC MENINGITIS CAUSED BY ANGIOSTRONGYLUS CANTONENSIS INFECTION

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  • 1 Section of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital. Kaohsiung City, Taiwan and National Yang-Ming University, Taipei, Taiwan, Republic of China; Department of Parasitology and Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China

Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. To assess the role of vascular endothelial growth factor in eosinophilic meningitis, vascular endothelial growth factor was measured in the cerebrospinal fluid (CSF) and blood of 9 patients with eosinophilic meningitis in a cohort study. VEGFCSF was detected in 8 (90%) of 9 eosinophilic meningitis patients (range, 45–2190 pg/mL) at presentation. The mean VEGFCSF at presentation, 1 week, and 2 weeks after admission was 568 pg/mL, 751 pg/mL, and 1031 pg/mL, respectively. There was an association between VEGFCSF, CSF protein, white cell count, and eosinophil counts. The VEGFSERUM fluctuated during the 6-month follow-up period. These results indicate that vascular endothelial growth factor may be associated with blood-brain barrier disruption in patients with eosinophilic meningitis.

INTRODUCTION

Angiostrongylus cantonensis, also known as the rat lung-worm, is the most common cause of eosinophilic meningitis in the Pacific Islands and Southeast Asia. Rats serve as the definitive host of the nematode. If an infection occurs in non-permissive hosts, including humans and mice, the development of the parasites will terminate at the young–adult worm stage in the brain and cause eosinophilic meningitis or meningoencephalitis.14 Several indices have been developed to assess the blood–brain barrier (BBB) integrity in an individual with a central nervous system infection. It was reported that most human immunodeficiency virus (HIV)-infected patients have pathologic cerebrospinal fluid (CSF) findings for at least one parameter, such as an elevated CSF total protein level, CSF white blood cell count, or CSF serum Immunoglobulin G ratio.5 In a mice animal model of eosinophilic meningitis caused by A. cantonensis infection, researchers showed that dysfunction of the BBB occurred in mice infected with A. cantonensis, evidenced by the high concentrations of protein and albumin, high leukocyte counts in CSF, high ratio of CSF/serum protein and albumin, and high permeability of BBB.6 Infection of the CSF causes a severe inflammatory reaction, mediated by pathogen products and host cytokines. This inflammatory reaction compromises the function of BBB, resulting in the exudation of plasma proteins and development of vasogenic brain edema, which contributes to cerebral dysfunction and brain damage.7 Vascular endothelial growth factor (VEGF), a 46-kDa glycosylated homodimeric protein, is a regulator of angiogenesis and a potent inducer of vascular permeability.8 VEGF is implicated in the pathogenesis of brain edema related to ischemia, trauma, bacterial meningitis, tuberculous meningitis, and tumors.7,9,10 To assess the role of VEGF in the pathophysiology of eosinophilic meningitis, dynamic VEGF levels were measured in CSF and serum of patients with eosinophilic meningitis in our cohort study.

MATERIALS AND METHODS

Patients.

A case of eosinophilic meningitis was clinically defined as presentation with an acute onset of headache, eosinophil pleocytosis in the blood/CSF, accompanied by at least of one of the following: fever, ataxia, visual disturbances, photophobia, nuchal rigidity, neck pain, hyperesthesias, or paresthesias.11 Three outbreaks of eosinophilic meningitis, caused by A. cantonensis occurred in Kaohsiung, Taiwan, in 1998, 1999, and 2001.1113 Most of the patients (77%) were adult, male, Thai laborers who had eaten raw golden apple snails within 3 weeks. Study subjects were derived from the second outbreak in 1999.12,13 All of the 9 Thai laborers received only analgesics or glycerol as treatment (or both). Each patient underwent a physical, neurologic, and ophthalmic examination. Laboratory tests were performed at the time of admission and spinal taps were performed on all patients. CSF analysis included cell count, glucose and protein levels, gram and acid-fast stains, India ink preparation, wet mount preparations for larvae, and measurement of cryptococcal antigen. The patients were observed daily during their hospital course. CSF was examined weekly until discharge. Blood was obtained weekly for the first 2 months, every other week for the next 2 months, and monthly thereafter for as long as 6 months. Blood and CSF samples were centrifuged (1700 g at 4°C) immediately, aliquoted, and stored at − 70°C.

Antibodies to A. cantonensis were detected in serum and CSF by a microenzyme-linked immunosorbent assay (ELISA) using young-adult worm antigen, with a molecular weight 204kD, and purified by monoclonal antibody.14

Vascular endothelial growth factor measurements.

Levels of VEGF in the serum and CSF (VEGFSERUM and VEGFCSF, respectively) were measured by enzyme immunoassay (Neogen Corporation, Lansing, MI). This Neogen’s Sandwich Human VEGF is a sandwich enzyme immunoassay (EIA), which measures the free forms of the cytokine VEGF165. Mouse monoclonal antibodies generated against human VEGF were used to capture human VEGF in a sample. Simultaneously, biotinylated rabbit anti-human VEGF polyclonal antibodies detected VEGF in the sample. The assay was visualized using a streptavidin alkaline phosphatase conjugate and an ensuring chromogenic substrate reaction. The assay sensitivity was 26.6 pg/ml, the range of detection 40.0 pg/ml to 5000 pg/ml, cross-reactivity < 0.5% against cytokine standards, intra-assay variation ± 7.3%, and inter-assay variation ± 10.5%. For patients with undetectable VEGF level, an arbitrary level of 25 pg/ml was used for statistical purpose.

Statistical analysis.

The association between VEGF and CSF laboratory abnormalities was analyzed with Pearson correlation test. A P value < 0.05 was considered statistically significant.

RESULT

All 9 patients in the cohort study were young Thai men. The source of epidemic was ingestion of raw snails seasoned with lemon juice and red pepper. Patients in this outbreak in 1999 only received supportive therapy. A total of 25 lumbar punctures were performed in these 9 patients. Nine lumbar punctures (5 and 4, respectively) were done in two patients due to recurrent headache. Headache, stiff neck, transient right facial palsy, ataxia, and diplopia recurred in 1 patient 24 days after treatment. A spinal tap revealed an elevated opening pressure of 250 mm H2O, a white cell count of 578 × 103 cells per μL with 24% eosinophils, a protein level of 165 mg/dL, and a glucose level of 43 mg/dL (initial CSF white cell count 1270 × 103cells per μL at admission). He was treated with intravenous glycerol for 7 days and recovered in a week. The serial VEGFCSF levels in this patient were 2190 pg/mL, 2200 pg/mL, 1550 pg/mL, 3640 pg/mL, and 45 pg/mL. Vomiting and headache developed in a second patient 15 days after treatment. A spinal tap revealed an elevated opening pressure of 240 mm H2O, a white cell count of 1110 × 103 cells per μL with 74% eosinophils, a protein level of 107 mg/dL, and a glucose level of 46 mg/dL (initial CSF white cell count 1390 × 103 cells per μL at admission). He recovered without treatment in about a week. The serial changes of VEGFCSF were 595 pg/mL at presentation, 160 pg/mL and 3250 pg/mL one and two weeks after admission, and 3640 pg/mL at recurrence of headache. VEGFCSF was detected in 8 (90%) of 9 eosinophilic meningitis patients (range, 45–2190 pg/mL) at presentation. The mean VEGFCSF at presentation, 1 week, and 2 weeks after admission was 568 pg/mL, 751 pg/mL, and 1031 pg/mL, respectively. The VEGFSERUM fluctuated during the 6-month follow-up. The mean CSF protein was 131 mg/dl at presentation and dropped to 81 mg/dl 2 weeks later. One patient had a rebound CSF protein level (141 mg/dl) on fifth lumbar puncture done 4 weeks later. CSF white cell count showed a time-dependent decrease, with mean levels of 618 cumm/ml, 320 cumm/ml, and 433 cumm/ml at presentation, 1 week, and 2 weeks after admission, respectively. The CSF white cell counts done during the fourth and fifth lumbar puncture in the two patients with recurrent headache were 369 cumm/ml and 667 cumm/ml, respectively. There was an association between VEGFCSF, total CSF protein concentrations, white cell counts, and eosinophil counts (Table 1).

DISCUSSION

In this study, we showed that VEGFCSF was detected in 8 (90%) of 9 eosinophilic meningitis patients (range, 45–2190 pg/mL) at presentation. There was an association between VEGFCSF, CSF protein, white cell count, and eosinophil counts. These results indicate that VEGF may play a role in the pathophysiology of eosinophilic meningitis. An increase in leukocyte count can be observed in the CSF of patients with central nervous system infection due to BBB damage.15,16 Our result showed that CSF white cell count had a time-dependent decrease, with mean levels of 618 cumm/ml, 320 cumm/ml, and 433 cumm/ml at presentation, 1 week, and 2 weeks after admission, respectively. The high white cell count in the CSF represented that the transmigration of leukocytes from the peripheral blood to the CSF in human infected with A. cantonensis becomes easier due to the presence of BBB dysfunction. The time-dependent decrease in CSF white cell count is compatible with the study by Dorta-Contreras and others,17 which showed that at the time of early clinical recovery, the blood–CSF barrier dysfunction was normalized in 75% of the patients. The CSF protein was elevated in our patients with eosinophilic meningitis. In the study of Yii,4 CSF protein was higher in patients with A. cantonensis-induced eosinophilic meningitis than the normal human. The explanation for an increase in CSF protein concentrations include a decreasing CSF flow rate18 and appearance of plasma proteins in the CSF due to presumed or overt disruption of blood–CSF barrier.19 Furthermore, Dorta-Contreras and others17 demonstrated that during the first 3 days of acute phase of eosinophilic meningoencephalitis, a blood–CSF barrier dysfunction occurred, usually due to a reduced CSF flow rate. Taken together, VEGF is associated with blood–brain barrier dysfunction in patients with eosinophilic meningitis.

Previous reports showed that VEGF can induce endothelial changes during bacterial meningitis, including increased vesicle transport and separation of endothelial intercellular tight junctions. Exposure of normal rat brain to VEGF results in BBB disruption, and VEGF is implicated in the formation of cerebral edema.9,20 Additionally, dexamethasone, which is used as adjunctive therapy in bacterial meningitis, suppresses tumor-associated brain edema by a mechanism involving downregulation of VEGF expression.21,22 Corticosteroid is also used as an adjunctive therapy in eosinophilic meningitis. Whether it is also mediated by a mechanism involving down-regulation of VEGF expression still unknown. In the clinical study of Chotmongkol and others,23 a 2-week course of prednisolone was beneficial in relieving the headache in patients with eosinophilic meningitis. In another study, researchers24 showed that a 1-week course of corticosteroid had the same beneficial effect as a 2-week course in increasing the number of patients who felt free from headache. In our study, VEGFCSF measured 1 and 2 weeks after presentation was significantly correlated with CSF abnormalities. The time course is consistent to the clinical treatment duration for 1 or 2 weeks, although we did not use any steroids in our patients.

One of our patients with recurrent headache received glycerol as an adjuvant therapy. Osmotherapy with mannitol, glycerol, or hypertonic saline is often used in patients with severe brain edema after stroke or neurotrauma.25 It can result in massive osmotic diuresis and fluid and electrolytes imbalance. As a result of a disrupted blood–brain barrier, the osmotic agents may leak into the brain parenchyma, with further disturbance of the osmotic gradient as a result.25 Interestingly, osmotherapy may even enhance disturbance of the blood–brain barrier. Mannitol cause the shrinkage of cerebral capillaries resulting in the opening of endothelial tight junction.26 This osmotic stress can involve in the calcium influx, nitric oxide, and cytoskeletal changes2628 and probably influence the measurement of VEGF in CSF.

The finding that VEGFCSF could not be detected in the CSF of all our patients with eosinophilic meningitis may be explained in several ways. First, locally secreted VEGF may induce endothelial permeability via the luminal receptors of endothelial cells, and may not be reflected in the CSF level. Disruption of the BBB may be further aggravated by VEGF secreted in the CSF via the abluminal receptors of endothelial cells.7,9 Second, the timing of sampling may affect VEGFCSF detection because the in vivo half-life of VEGFCSF is unknown.7 Third, not every patient in our study had CSF abnormalities. Finally, BBB disruption during eosinophilic meningitis involves a complex interaction between eosinophils and mediators, such as interleukin-4, interleukin-5, platelet-activating factor, nitric oxide, and matrix metalloproteinases, which might induce BBB permeability, independent of VEGF.29

We did not measure the serum/CSF albumin for VEGF index. VEGF levels were higher in the serum compared with the CSF, therefore the possibility of VEGF accumulation in CSF caused by passive influx instead of intrathecal production can not be excluded. However, it remains to be determined whether this is due to a fairly low production of VEGF by inflammatory cells, rapid degradation of immunoreactive VEGF, or binding of VEGF to soluble or cell-bound VEGF receptors.30

Based on our small cases series, we found that patients with eosinophilic meningitis and presence of VEGF proteins in CSF could be associated with disruption of BBB. There was an association between VEGFCSF, CSF protein, white cell count, and eosinophil counts. The VEGFSERUM fluctuated during the 6-month follow-up period. However, larger cases studies are needed to justify this conclusion.

Table 1

Pearson correlation test showed an association between VEGFCSF, CSF protein, CSF white cell counts and CSF eosinophil counts

VEGFCSF1VEGFCSF2VEGFCSF3
VariablerprPrp
VEGFCSF1, VEGFCSF2, VEGFCSF3, represent the CSF VEGF level at presentation (n = 7), 1 week (n = 9), and 2 weeks later (n = 6). CSF protein 1, CSF protein 2, CSF protein 3 are the protein concentration in CSF at presentation, 1 week, and 2 weeks after admission. CSF wbc1, CSF wbc2, CSF wbc3 show the white cell count in CSF at presentation, 1 week, and 2 weeks later. CSF eosin represented CSF eosinophil counts at presentation.
* showed P < 0.05.
CSF protein10.3340.4650.7880.035*0.7880.035*
CSF protein20.1280.7420.8290.006*0.6410.063
CSF protein30.2370.7010.8600.0610.8720.054
CSF wbc10.3370.4600.7950.033*0.7950.033*
CSF wbc20.5050.1660.8170.007*0.932< 0.001*
CSF wbc30.7540.0840.5770.2310.8860.019*
CSF eosin0.150.001*0.8060.009*0.6850.042*

*

Address correspondence to Professor Chuan-Min Yen, Department of Parasitology, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan, Republic of China. E-mail: hctsai1011@yahoo.com.tw

Authors’ addresses: Hung-Chin Tsai, Yung-Ching Liu, and Susan Shin-Jung Lee, Section of Infectious Diseases and Department of Medicine, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung, 813, Taiwan, Telephone: 886-7-3468299, Fax: 886-7-3468292. Eng-Rin Chen and Chuan-Min Yen, Department of Parasitology, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan, Telephone: 886-7-3121101 ext. 2169.

Acknowledgment: This work is supported by Grant VGHKS94-020 and VGHKS95-014 from Kaohsiung Veterans General Hospital, Taiwan.

REFERENCES

  • 1

    Beaver PC, Rosen L, 1945. Memorandum on the first report of Angiostrongylus in man by Nomura and Lin. Am J Trop Med Hyg 13 :589–590.

  • 2

    Rosen L, Chappell R, Laqueur GL, 1962. Eosinophilic meningoencephalitis caused by a metastrongylid lung worm of rats. JAMA 179 :620–624.

    • Search Google Scholar
    • Export Citation
  • 3

    Punyagupta S, Juttijudata P, Bunnag T, 1975. Eosinophilic meningitis in Thailand: clinical studies of 484 typical cases probably caused by Angiostrongylus. Am J Trop Med Hyg 24 :921–931.

    • Search Google Scholar
    • Export Citation
  • 4

    Yii CY, 1976. Clinical observations on eosinophilic meningitis and meningoencephalitis caused by Angiostrongylus cantonensis on Taiwan. Am J Trop Med Hyg 25 :233–249.

    • Search Google Scholar
    • Export Citation
  • 5

    Marshall DW, Brey RL, Cahill WT, Houk RW, Zajac RA, Boswell RN, 1988. Spectrum of cerebrospinal fluid findings in various stages of human immunodeficiency virus infection. Arch Neurol 45 :954–958.

    • Search Google Scholar
    • Export Citation
  • 6

    Lee JD, Tsai LY, Chen CH, Wang JJ, Hsiao JK, Yen CM, 2006. Blood-brain barrier dysfunction occurring in mice infected with Angiostrongylus cantonensis. Acta Trop 97 :204–211.

    • Search Google Scholar
    • Export Citation
  • 7

    van der Flier M, Stockhammer G, Vonk GJ, Nikkels PG, van Diemen-Steenvoorde RA, van der Vlist GJ, Rupert SW, Schmutzhard E, Gunsilius E, Gastl G, Hoepelman AI, Kimpen JL, Geelen SP, 2001. Vascular endothelial growth factor in bacterial meningitis: detection in cerebrospinal fluid and localization in postmortem brain. J Infect Dis 183 :149–153.

    • Search Google Scholar
    • Export Citation
  • 8

    Connolly DT, 1991. Vascular permeability factor: a unique regulator of blood vessel function. J Cell Biochem 47 :219–223.

  • 9

    van Bruggen N, Thibodeaux H, Palmer JT, Lee WP, Fu L, Cairns B, Tumas D, Gerlai R, Williams SP, van Lookeren Campagne M, Ferrara N, 1999. VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain. J Clin Invest 104 :1613–1620.

    • Search Google Scholar
    • Export Citation
  • 10

    van der Flier M, Hoppenreijs S, van Rensburg AJ, Ruyken M, Kolk AH, Springer P, Hoepelman AI, Geelen SP, Kimpen JL, Schoeman JF, 2004. Vascular endothelial growth factor and blood-brain barrier disruption in tuberculous meningitis. Pediatr Infect Dis J 23 :608–613.

    • Search Google Scholar
    • Export Citation
  • 11

    Tsai HC, Lee SS, Huang CK, Yen CM, Chen ER, Liu YC, 2004. Outbreak of eosinophilic meningitis associated with drinking raw vegetable juice in southern Taiwan. Am J Trop Med Hyg 71 :222–226.

    • Search Google Scholar
    • Export Citation
  • 12

    Tsai HC, Liu YC, Kunin CM, Lee SS, Chen YS, Lin HH, Tsai TH, Lin WR, Huang CK, Yen MY, Yen CM, 2001. Eosinophilic meningitis caused by Angiostrongylus cantonensis: report of 17 cases. Am J Med 111 :109–114.

    • Search Google Scholar
    • Export Citation
  • 13

    Tsai HC, Liu YC, Kunin CM, Lai PH, Lee SS, Chen YS, Wann SR, Lin WR, Huang CK, Ger LP, Lin HH, Yen MY, 2003. Eosinophilic meningitis caused by Angiostrongylus cantonensis associated with eating raw snails: correlation of brain magnetic resonance Imaging scans with clinical findings. Am J Trop Med Hyg 68 :281–285.

    • Search Google Scholar
    • Export Citation
  • 14

    Chye SM, Chang JH, Yen CM, 2000. Immunodiagnosis of human eosinophilic meningitis using an antigen of Angiostrongylus cantonensis L5 with molecular weight 204KD. Acta Trop 75 :9–17.

    • Search Google Scholar
    • Export Citation
  • 15

    Bisser S, Lejon V, Preux PM, Bouteille B, Stanghellini A, Jauberteau MO, Buscher P, Dumas M, 2002. Blood–cerebrospinal fluid barrier and intrathecal immunoglobulins compared to field diagnosis of central nervous system involvement in sleeping sickness. J Neurol Sci 193 :127–135.

    • Search Google Scholar
    • Export Citation
  • 16

    Quagliarello V, Scheld WM, 1992. Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med 327 :864–872.

  • 17

    Dorta-Contreras AJ, Reiber H, 1998. Intrathecal synthesis of immunoglobulins in eosinophilic meningoencephalitis due to Angiostrongylus cantonensis. Clin Diagn Lab Immunol 5 :452–455.

    • Search Google Scholar
    • Export Citation
  • 18

    Reiber H, 1994. Flow rate of cerebrospinal fluid (CSF)—a concept common to normal blood–CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci 122 :189–203.

    • Search Google Scholar
    • Export Citation
  • 19

    Marchi N, Fazio V, Cucullo L, Kight K, Masaryk T, Barnett G, Vogelbaum M, Kinter M, Rasmussen P, Mayberg MR, Janigro D, 2003. Serum transthyretin monomer as a possible marker of blood–to–CSF barrier disruption. J Neurosci 23 :1949–1955.

    • Search Google Scholar
    • Export Citation
  • 20

    Proescholdt MA, Heiss JD, Walbridge S, Muhlhauser J, Capogrossi MC, Oldfield EH, Merrill MJ, 1999. Vascular endothelial growth factor (VEGF) modulates vascular permeability and inflammation in rat brain. J Neuropathol Exp Neurol 8 :613–627.

    • Search Google Scholar
    • Export Citation
  • 21

    McIntyre PB, Berkey CS, King SM, Schaad UB, Kilpi T, Kanra GY, Perez CM, 1997. Dexamethasone as adjunctive therapy in bacterial meningitis: a meta-analysis of randomized clinical trials since 1988. JAMA 278 :925–931.

    • Search Google Scholar
    • Export Citation
  • 22

    Heiss JD, Papavassiliou E, Merrill MJ, Nieman L, Knightly JJ, Walbridge S, Edwards NA, Oldfield EH, 1996. Mechanism of dexamethasone suppression of brain tumor–associated vascular permeability in rats: involvement of the glucocorticoid receptor and vascular permeability factor. J Clin Invest 98 :1400–1408.

    • Search Google Scholar
    • Export Citation
  • 23

    Chotmongkol V, Sawanyawisuth K, Thavornpitak Y, 2000. Corticosteroid treatment of eosinophilic meningitis. Clin Infect Dis 31 :660–662.

  • 24

    Sawanyawisuth K, Limpawattana P, Busaracome P, Ninpaitoon B, Chotmongkol V, Intapan PM, Tanawirattananit S, 2004. 1-week course of corticosteroids in the treatment of eosinophilic meningitis. Am J Med 117 :802–803.

    • Search Google Scholar
    • Export Citation
  • 25

    Kaal EC, Vecht CJ, 2004. The management of brain edema in brain tumors. Curr Opin Oncol 16 :593–600.

  • 26

    Kroll RA, Neuwelt EA, 1998. Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and other means. Neurosurgery 42 :1083–1099.

    • Search Google Scholar
    • Export Citation
  • 27

    Berk BC, Corson MA, Peterson TE, Tseng H, 1995. Protein kinases as mediators of fluid shear stress stimulated signal trans-duction in endothelial cells: a hypothesis for calcium-dependent and calcium-independent events activated by flow. J Biomech 28 :1439–1450.

    • Search Google Scholar
    • Export Citation
  • 28

    Dascalu A, Oron Y, Nevo Z, Korenstein R, 1995. Hyperosmotic modulation of the cytosolic calcium concentration in a rat osteoplast-like cell line. J Physiol 486 :97–104.

    • Search Google Scholar
    • Export Citation
  • 29

    Leib SL, Tauber MG, 1999. Pathogenesis of bacterial meningitis. Infect Dis Clin North Am 13 :527–548.

  • 30

    Stockhammer G, Poewe W, Burgstaller S, Deisenhammer F, Muigg A, Kiechl S, Schmutzhard E, Maier H, Felber S, Schumacher P, Gunsilius E, Gastl G, 2000. Vascular endothelial growth factor in CSF: a biological marker for carcinomatous meningitis. Neurology 54 :1670–1676.

    • Search Google Scholar
    • Export Citation
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