What does an elevated IgG (Immunoglobulin G) index signify?

Elevated IgG Index Significance in Neurological Disorders

An IgG index of 88 strongly suggests intrathecal IgG synthesis and is highly indicative of multiple sclerosis (MS), requiring prompt neurological evaluation and further diagnostic workup. This markedly elevated value far exceeds normal reference ranges and represents significant immune activity within the central nervous system.

Understanding IgG Index

The IgG index is a measure used to detect intrathecal (within the cerebrospinal fluid) immunoglobulin G production. It's calculated using the ratio of CSF/serum IgG to CSF/serum albumin, which helps differentiate between blood-brain barrier dysfunction and true intrathecal antibody synthesis.

• Normal IgG index: <0.7
• Elevated IgG index: >0.7
• Value of 88: Dramatically elevated, indicating significant intrathecal IgG synthesis

Clinical Significance

Multiple Sclerosis

• Primary consideration with such a high IgG index
• According to the International Panel on MS Diagnosis, elevated IgG index is a supportive paraclinical finding for MS diagnosis 1
• Recent research shows IgG index has a positive predictive value >99% for oligoclonal bands, which are a key diagnostic marker for MS 2

Other Potential Causes

1. Inflammatory CNS Disorders:

   • Subacute sclerosing panencephalitis (SSPE)
   • Neuromyelitis optica
   • Acute disseminated encephalomyelitis

2. CNS Infections:

   • Viral encephalitis
   • Neurosyphilis
   • Lyme neuroborreliosis
   • Cryptococcal meningitis

3. Autoimmune Disorders with CNS involvement:

   • Systemic lupus erythematosus
   • Sjögren's syndrome
   • Sarcoidosis

Diagnostic Value Compared to Other Tests

• IgG index is less sensitive than oligoclonal bands (OCBs) for MS diagnosis
• Studies show IgG index detects intrathecal synthesis in 76.7% of MS patients versus 93.3% detection with OCBs 2
• However, an elevated IgG index has excellent specificity with minimal false positives compared to quantitative measurements 3

Recommended Next Steps

1. Neurological Consultation: Immediate referral to a neurologist

2. Additional CSF Studies:

   • Oligoclonal band analysis (gold standard)
   • Cell count and differential
   • Protein and glucose levels
   • Specific antibody indices if infection suspected

3. Neuroimaging:

   • MRI brain and spinal cord with contrast (to assess for demyelinating lesions)
   • Look for lesions disseminated in space and time

4. Evoked Potentials:

   • Visual evoked potentials
   • Somatosensory evoked potentials

5. Rule out mimics:

   • Serum autoimmune panel
   • Infectious disease workup
   • Vascular imaging if indicated

Clinical Pearls

• An IgG index of 88 is extremely high and virtually pathognomonic for significant CNS inflammation
• While MS is the most likely diagnosis, other inflammatory and infectious CNS disorders must be considered
• The 2017 McDonald criteria for MS diagnosis allows CSF-specific oligoclonal bands to substitute for dissemination in time
• Isoelectric focusing for oligoclonal bands is more sensitive than IgG index but takes longer to perform 2
• Normal IgG levels do not exclude MS, as approximately 7-10% of definite MS cases may have normal CSF findings 1

This dramatically elevated IgG index requires urgent evaluation, as early diagnosis and treatment of the underlying condition (particularly if MS) can significantly impact long-term morbidity and quality of life outcomes.