What is the definition of hypoglycorrhachia in cerebrospinal fluid (CSF)?

Definition of Hypoglycorrhachia in Cerebrospinal Fluid (CSF)

Hypoglycorrhachia is defined as an abnormally low glucose concentration in the cerebrospinal fluid (CSF), typically less than 40 mg/dL (2.2 mmol/L) or a CSF-to-serum glucose ratio less than 0.5. This finding is an important diagnostic marker in various neurological conditions.

Diagnostic Criteria

The definition of hypoglycorrhachia can be approached in two ways:

1. Absolute CSF glucose value:

   • Most commonly defined as CSF glucose <40 mg/dL (2.2 mmol/L) 1
   • Some studies use a threshold of <45 mg/dL (2.5 mmol/L) 2

2. CSF-to-serum glucose ratio:

   • Ratio <0.5 (CSF glucose is less than half of the simultaneous serum glucose) 1, 3
   • This ratio accounts for the dynamic equilibrium between blood and CSF glucose levels

Clinical Significance

Hypoglycorrhachia is an important diagnostic finding with significant prognostic implications:

• Patients with hypoglycorrhachia have significantly higher rates of adverse clinical outcomes (22.4% vs 8.9%) compared to those without hypoglycorrhachia 2
• It serves as a marker for potentially urgent treatable conditions 2
• The presence of hypoglycorrhachia should prompt consideration of specific etiologies that require immediate intervention

Common Etiologies

Hypoglycorrhachia is associated with various conditions:

1. Infectious causes:

   • Bacterial meningitis (24% of cases) 1
   • Fungal meningitis (15% of cases overall, 38% in HIV-infected patients) 1
   • Tuberculous meningitis 4
   • Viral meningitis (6% of cases) 1
   • Neurosyphilis (4% of cases) 1
   • Cerebral toxoplasmosis (3% of cases) 1

2. Non-infectious causes:

   • Stroke/intracranial hemorrhage (13% of cases) 1
   • Malignancy/meningeal carcinomatosis (11% of cases) 1
   • Neurosarcoidosis (4% of cases) 1
   • Systemic hypoglycemia 3

In patients without HIV or neurosurgical history, non-infectious etiologies (stroke/hemorrhage and malignancy) are actually the most common causes of hypoglycorrhachia 1.

Pathophysiological Mechanisms

The mechanism of hypoglycorrhachia appears to be multifactorial:

• The presence of microorganisms capable of catabolizing glucose is a major determinant 5
• CSF inflammation alone is not sufficient to cause significant hypoglycorrhachia 5
• Elevated CSF protein levels correlate more strongly with low CSF glucose than leukocyte count does (R² = 36%, p < 0.001) 5

Diagnostic Value

When evaluating CSF samples:

• CSF glucose <2.2 mmol/L (40 mg/dL) has moderate sensitivity (68%) but high specificity (96%) for diagnosing conditions like tuberculous meningitis 4
• CSF-to-serum glucose ratio <0.5 has higher sensitivity (90%) for diagnosing conditions like tuberculous meningitis 4
• CSF protein >1 g/L combined with hypoglycorrhachia is highly specific (94%) for certain infections like tuberculous meningitis 4

Clinical Example

In CMV polyradiculomyelopathy, the CSF typically demonstrates a neutrophilic pleocytosis (usually 100-200 neutrophils/μL and some erythrocytes) accompanied by hypoglycorrhachia and elevated protein levels 6.

Conclusion

Hypoglycorrhachia is a valuable diagnostic finding that should prompt consideration of both infectious and non-infectious etiologies. The combination of hypoglycorrhachia with other CSF parameters (protein, cell count, microbiological studies) provides important diagnostic information to guide appropriate management of potentially serious neurological conditions.