Neurofilament Light Chain as a Biomarker in CIDP
Yes, serum neurofilament light chain (NfL) is a useful parameter for assessing disease activity and treatment response in CIDP, though it is not currently part of standard diagnostic criteria.
Role of NfL in CIDP Assessment
NfL serves as a marker of active neuroaxonal damage rather than a diagnostic criterion for CIDP itself. The American Academy of Neurology notes that NfL is a neuronal cytoskeleton protein that reflects neuroaxonal injury when detected in blood or cerebrospinal fluid 1. While nerve biopsy is generally accepted as useful in atypical forms of CIDP, the literature provides insufficient evidence to recommend when nerve biopsy may be useful in standard evaluation 2.
Disease Activity Monitoring
Elevated serum NfL levels correlate strongly with active disease in CIDP patients. Treatment-naive CIDP patients demonstrate significantly higher NfL levels (median 23.4 pg/mL) compared to stable patients on maintenance therapy (median 7.7 pg/mL) 3. Baseline NfL levels in newly diagnosed CIDP patients are significantly elevated compared to healthy controls and decrease significantly after one month of intravenous immunoglobulin (IVIg) treatment 4.
Among patients receiving maintenance IVIg, those with unstable disease show significantly higher NfL concentrations than clinically stable patients 5. A threshold of >16.6 pg/mL distinguishes unstable from stable treated CIDP with 86.7% sensitivity and 66.7% specificity 5.
Prognostic Value
NfL levels above the median cohort value (28.3 pg/mL) predict poor outcomes with high accuracy. Patients with elevated NfL demonstrate:
- 6.6-fold increased odds of 1-year disease progression (defined as ≥4-point decrease on 80-point MRC sum-score) 6
- 6.4-fold increased odds of insufficient treatment response requiring therapy switch 6
- 10.1-fold increased odds of demonstrating either disease progression or therapy non-response when analyzed together 6
The correlation between NfL at treatment withdrawal and likelihood of relapse (r = 0.72) suggests higher levels indicate subclinical disease activity 5.
Clinical Correlation
NfL levels correlate with functional disability measures in treatment-naive patients, including INCAT scores (p = 0.007), I-RODS scores (p = 0.004), and MRC sum-scores (p = 0.016) 3. However, this correlation is not observed in patients receiving stable maintenance therapy 3. NfL also correlates with the average amplitude of distal compound muscle action potentials in the most affected limb (p = 0.043) 3.
Important Caveats and Limitations
Age-Related Confounding
The American Geriatrics Society emphasizes that age is the most important confounding factor in interpreting NfL, with a strong age-dependent relationship that complicates clinical evaluation, especially in patients over 70 years 1. Age-adjusted reference ranges must be used for accurate interpretation 1.
Non-Specificity
The National Institute of Neurological Disorders and Stroke advises against interpreting NfL in isolation, as it reflects only the degree of neuronal damage, not the underlying pathology 1. NfL is not specific for CIDP versus other causes of peripheral nerve injury 2. Other factors influencing NfL levels include peripheral neuropathies of other etiologies, body mass index, and renal disease 1.
Divergent Evidence in Chronic Disease
While multiple studies show utility in acute/active CIDP, evidence regarding NfL as a predictor of disease progression in chronic CIDP is divergent, with only two out of five studies finding significant associations between NfL levels and clinical outcomes 7. NfL may not serve as a reliable biomarker for slowly progressive polyneuropathies 7.
Practical Application Algorithm
For treatment-naive CIDP patients:
- Measure baseline serum NfL before initiating therapy 4, 3
- Remeasure at 1 month and 5 months post-treatment initiation 4, 3
- Expect significant reduction if treatment is effective 4, 3
For patients on maintenance therapy:
- Measure NfL when clinical stability is uncertain 5
- Values >16.6 pg/mL suggest subclinical disease activity requiring treatment adjustment 5
- Consider NfL measurement before treatment withdrawal to assess relapse risk 5
For prognostic assessment:
- Values >28.3 pg/mL (or above median for your laboratory) indicate high risk for progression and treatment failure 6
- Combine with clinical disability scales (INCAT, I-RODS, MRC-SS) for comprehensive assessment 3
Always evaluate confounding factors:
- Obtain renal function tests 1
- Use age-adjusted reference ranges 1
- Exclude other causes of peripheral neuropathy 1
Current Guideline Status
NfL is not included in the European Federation of Neurological Societies/Peripheral Nerve Society diagnostic criteria for CIDP 6. Standard diagnostic evaluation relies on clinical symptoms, signs, and electrodiagnostic criteria 8. Autonomic testing may be considered to document autonomic nervous system dysfunction, and skin biopsy for small fiber assessment, but these are adjunctive rather than diagnostic 2.