The challenge of profound hypoglycorrhachia: two cases of sarcoidosis and review of the literature

Sarva, Harini; Chapman, R. Cecil; Omoregie, Eghosa; Abrams, Charles K.

doi:10.1007/s10067-011-1834-y

Cited by 10 publications

(5 citation statements)

References 43 publications

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“…These cases were for the most part (8/11) biopsy-proven neurosarcoidosis, confirming previous reports. 11 , 12 , 21 As exemplified by the typical granulomatous inflammation found on pathology, neurosarcoidosis resembles inflammatory responses to microbial meningitis. Little is known about the exact molecular pathways of neuroinflammation in neurosarcoidosis, but whole blood transcriptome analyses of patients with active pulmonary sarcoidosis resemble that of inflammatory responses to active mycobacterial infection.…”

Section: Discussionmentioning

confidence: 99%

Pleocytosis is not fully responsible for low CSF glucose in meningitis

Baud

Vitt

Robbins

et al. 2018

Neurol Neuroimmunol Neuroinflamm

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Objective:The mechanism of hypoglycorrhachia—low CSF glucose—in meningitis remains unknown. We sought to evaluate the relative contribution of CSF inflammation vs microorganisms (bacteria and fungi) in lowering CSF glucose levels.Methods:We retrospectively categorized CSF profiles into microbial and aseptic meningitis and analyzed CSF leukocyte count, glucose, and protein concentrations. We assessed the relationship between these markers using multivariate and stratified linear regression analysis for initial and repeated CSF sampling. We also calculated the receiver operating characteristics of CSF glucose and CSF-to-serum glucose ratios to presumptively diagnose microbial meningitis.Results:We found that increasing levels of CSF inflammation were associated with decreased CSF glucose levels in the microbial but not aseptic category. Moreover, elevated CSF protein levels correlated more strongly than the leukocyte count with low CSF glucose levels on initial (R2 = 36%, p < 0.001) and repeated CSF sampling (R2 = 46%, p < 0.001). Hypoglycorrhachia (<40 mg/dL) was observed in 50.1% of microbial cases, but only 9.6% of aseptic cases, most of which were neurosarcoidosis. Absolute CSF glucose and CSF-to-serum glucose ratios had similar low sensitivity and moderate-to-high specificity in diagnosing microbial meningitis at thresholds commonly used.Conclusions:The main driver of hypoglycorrhachia appears to be a combination of microbial meningitis with moderate to high degrees of CSF inflammation and proteins, suggesting that the presence of microorganisms capable of catabolizing glucose is a determinant of hypoglycorrhachia in meningitis. A major notable exception is neurosarcoidosis. Low CSF glucose and CSF-to-serum glucose ratios are useful markers for the diagnosis of microbial meningitis.

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Section: Discussionmentioning

confidence: 99%

Pleocytosis is not fully responsible for low CSF glucose in meningitis

Baud

Vitt

Robbins

et al. 2018

Neurol Neuroimmunol Neuroinflamm

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“…On the other hand, many infectious and sterile inflammations have been associated with severely reduced glucose concentrations, including bacterial, mycobacterial, and fungal central nervous system (CNS) infections (15) or pleural effusions (16, 17). In addition, non-infectious inflammatory conditions can also be associated with very low glucose concentrations, including sarcoidosis (18), rheumatoid meningitis (19), and rheumatoid pleurisy (20–22), as well as CNS involvement and pleural effusion associated with systemic lupus erythematosus (15, 23). In general, any factors compromising blood flow and glucose supply—like conditions of impaired microcirculation due to septic shock, arteriosclerotic vessel damage, or vasculitis—are likely to tilt the balance of glucose supply and lead to glucose deprivation.…”

Section: Introductionmentioning

confidence: 99%

Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in Glucose-Deprived Monocytes

et al. 2017

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Monocytes enter sites of microbial or sterile inflammation as the first line of defense of the immune system and initiate pro-inflammatory effector mechanisms. We show that activation with bacterial lipopolysaccharide (LPS) induces them to undergo a metabolic shift toward aerobic glycolysis, similar to the Warburg effect observed in cancer cells. At sites of inflammation, however, glucose concentrations are often drastically decreased, which prompted us to study monocyte function under conditions of glucose deprivation and abrogated Warburg effect. Experiments using the Seahorse Extracellular Flux Analyzer revealed that limited glucose supply shifts monocyte metabolism toward oxidative phosphorylation, fueled largely by fatty acid oxidation at the expense of lipid droplets. While this metabolic state appears to provide sufficient energy to sustain functional properties like cytokine secretion, migration, and phagocytosis, it cannot prevent a rise in the AMP/ATP ratio and a decreased respiratory burst. The molecular trigger mediating the metabolic shift and the functional consequences is activation of AMP-activated protein kinase (AMPK). Taken together, our results indicate that monocytes are sufficiently metabolically flexible to perform pro-inflammatory functions at sites of inflammation despite glucose deprivation and inhibition of the LPS-induced Warburg effect. AMPK seems to play a pivotal role in orchestrating these processes during glucose deprivation in monocytes.

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“…1,2 In order to have a reliable CSF to serum glucose ratio, the time between the two determinations should be done within 60 minutes of each other. 2 Hypoglycorrhachia is usually suggestive of bacterial, tuberculous and fungal meningitis but has been reported in other cases such as in viral/aseptic meningitis 4–7 , leptomeningeal carcinomatosis 8 , subarachnoid hemorrhage 9 , Lyme meningitis 10 , neurobrucellosis 11 , and neurosarcoidosis 12 . The only study to our knowledge that has evaluated the differential diagnosis of hypoglycorrhachia was done in children and published in 1976 before the advent of molecular diagnostic tests 13 .…”

Section: Introductionmentioning

confidence: 99%

Hypoglycorrhachia in adults with community-acquired meningitis: etiologies and prognostic significance

Shrikanth

Salazar

Khoury

et al. 2015

International Journal of Infectious Diseases

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Study objectives Hypoglycorrhachia (CSF glucose < 45mg/dL) has been identified as a prognostic factor in patients with meningitis. We analyzed the differential diagnosis of hypoglycorrhachia and its clinical significance. Methods Retrospective study of 620 adult patients with community acquired meningitis [CSF WBC >5 cells/mm3, absence of a CSF shunt or recent neurosurgical procedure (< 1 month)] at 8 Memorial Hermann Hospitals in Houston, TX from January, 2005 to December, 2010. An adverse clinical outcome was defined as a Glasgow outcome scale of 4 or less. Results Out of 620 patients with meningitis, 116 (19%) had hypoglycorrachia. Etiologies of hypoglycorrhachia were idiopathic (40), bacterial (27), cryptococcal (26), viral (15), and tuberculous (4). Patients with hypoglycorrachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status and focal neurological deficits compared to those patients without hypoglycorrachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions and abnormal cranial imaging (p<005). Furthermore, patients with hypoglycorrachia had more adverse clinical outcomes [26 out of 116 (22.4%) vs. 45 out of 504 (8.9%)] (p< 0.001). Conclusion Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis.

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The challenge of profound hypoglycorrhachia: two cases of sarcoidosis and review of the literature

Cited by 10 publications

References 43 publications

Pleocytosis is not fully responsible for low CSF glucose in meningitis

Pleocytosis is not fully responsible for low CSF glucose in meningitis

Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in Glucose-Deprived Monocytes

Hypoglycorrhachia in adults with community-acquired meningitis: etiologies and prognostic significance

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