Oligoclonal Bands in Cerebrospinal Fluid
Diagnostic Significance
Oligoclonal bands (OCBs) in CSF are a highly sensitive marker of intrathecal IgG synthesis and serve as a cornerstone for diagnosing multiple sclerosis, where they are present in up to 98% of patients in Central and Northern Europe, though their presence is non-specific and can occur in other inflammatory CNS conditions. 1
Detection and Interpretation
CSF analysis should be routinely performed in patients with a first clinical event suggestive of MS, particularly when MRI criteria fall short or clinical presentation is atypical. 2
Isoelectric focusing (IEF) on agarose gels followed by immunoblotting is the recommended technique for OCB detection, analyzing paired undiluted CSF and serum samples. 3
Positive CSF is defined as oligoclonal IgG bands detected by isoelectric focusing that are different from serum bands OR an elevated IgG index. 2
The avidin-biotin IEF method demonstrates OCBs in CSF from all patients with MS and has optimal specificity since IgG is exclusively detected. 4
Role in Multiple Sclerosis Diagnosis
The presence of two or more MRI lesions consistent with MS plus positive CSF can substitute for full MRI dissemination in space (DIS) criteria. 2
In patients not satisfying DIS criteria for MS, the presence of 3 periventricular lesions combined with age or presence of oligoclonal bands is helpful in identifying those at risk for MS. 1
OCBs were demonstrated in CSF from all 58 patients with MS in a consecutive series of 1,114 neurological patients. 4
The detection of oligoclonal bands in CSF is a non-specific indicator of an inflammatory process in the CNS. 1
Differential Diagnosis Considerations
OCBs are present in only 12-13% of patients with MOG encephalomyelitis (MOG-EM), making their absence a useful distinguishing feature from MS, though positive OCBs do NOT exclude MOG-EM. 1
Many MOG-EM patients previously falsely diagnosed with MS were atypical in that they had no OCB. 1
OCBs can be observed in other CNS diseases including aseptic nervous system infections (8 of 29 patients) and 9% of patients with other neurological disorders considered non-inflammatory at primary evaluation. 4
OCBs appear in CSF from patients with inflammatory pathology such as neurosyphilis, acute idiopathic polyneuropathy, and subacute sclerosing panencephalitis. 5
Geographic and Population Variations
The frequency of OCBs in MS may be lower in Asian patients (40-80% in Japan) and in some European regions such as Sardinia (84%). 1
In the pediatric population, the presence of even one clinically silent T2 hyperintense brain lesion in children with optic neuritis is highly associated with MS diagnosis confirmation. 1
Special Patterns and Clinical Implications
A single abnormal IgG band confined to CSF (found in 0.55% of samples) may suggest a disease other than MS and mark an aggressive course with affective disorder in those who do have MS. 6
Most gamma-globulin bands are identified as IgG, but some bands are identified as kappa or lambda free light chains. 7
Intrathecal synthesis of HSV-specific IgG antibodies is normally detected after 10-14 days of illness and can persist for several years; immunoblotting of oligoclonal bands against viral proteins from HSV can be used to detect anti-HSV antibody. 1
Critical Pitfalls
Negative or atypical MRI/CSF findings should always prompt consideration of alternative diagnoses including cerebral ischemia, infections (HTLV1, Lyme), paraneoplastic disorders, acute disseminated encephalomyelitis, neuromyelitis optica, and leukodystrophies. 2
Technical issues including blot, staining, and IEF reproducibility as well as operator-dependent pattern interpretations can cause misinterpretations with significant diagnostic implications. 3
Intrathecal immune responses may be delayed or absent when antiviral therapy is started early in viral encephalitis. 1