Image of an injection during diagnosing ms
#Cognition #Imaging #Physical Disability
  • Diagnosis: Oligoclonal banding is an accurate and reliable laboratory test to help diagnose patients with multiple sclerosis (MS)1-5
  • Prognosis: Research has found that patients with oligoclonal bands (OCB) are more likely to experience greater disability over time (both physical and cognitive), indicating that OCBs may have prognostic value4,6-8
  • Grey Matter (GM) Pathology: A 10-year observational study also revealed that OCBs may be correlated with more severe GM pathology, with OCB-positive patients having 2.7 times more cortical lesions over time than patients with no OCBs8

The Difficulty of Diagnosing MS

Multiple sclerosis is a debilitating neurological disease that can be complex and unpredictable, making it difficult to diagnose.5,9,10 Although advances in technology have helped improve diagnosis overall, it can still be challenging to accurately identify some patients. In one study of 50 MS patients, 58% were misdiagnosed and told that they had another condition (most commonly a psychiatric disorder, a viral infection, or orthopedic condition).11 In some cases, patients remain misdiagnosed for as long as 10 to 15 years causing clinical, economic, and psychosocial problems.9,12

The best tool for accurately identifying patients with MS is magnetic resonance imaging (MRI), a radiographic technique that has revolutionized central nervous system (CNS) imaging.13 However, MRI scans can sometimes be misinterpreted, a factor that commonly contributes to misdiagnosis.12 Fortunately, there are other methods available to help diagnose MS, including optical coherence tomography, evoked potential assessments, and cerebrospinal fluid (CSF) tests.5

OCB: A Uniquely Robust Diagnostic Tool

One of the most effective tools for diagnosing patients with MS is a laboratory test that looks for elevated levels of gamma globulin in the CSF.14-17 Gamma globulins are immune-based proteins that show up in laboratory tests as a series of lines, known as oligoclonal bands.16 This banding pattern can be found in more than 95% of patients with MS,6,7,18,19 making it a highly accurate means of diagnosing the disease. Based on decades of research, oligoclonal banding is now considered a hallmark sign of MS.8,19,20

≈95%

of patients with MS have oligoclonal banding in their CSF6

More recently, research has shown that oligoclonal banding can also help predict both the short- and long-term prognosis of patients with MS.4,6-8 In one study, patients with 10 or more oligoclonal bands were found to have more relapses and greater clinical progression over the short term.4 In another study, patients with OCBs at the onset of MS had more severe GM pathology and greater disability 10 years after diagnosis.8 Oligoclonal banding is the only established immunological biomarker in MS that helps with both diagnosis and prognosis.19

Built on Decades of Research

The value of gamma globulins in diagnosing MS was first noted in 1942, when Kabat et al published a groundbreaking clinical study. This research showed that patients with MS had high levels of immunoglobulin G (IgG) in their cerebrospinal fluid, but not in their blood. When IgG levels are elevated, it can indicate that the body’s immune system has become overly active. The fact that levels were elevated in the CSF, but not in the blood, indicates the presence of a CNS-specific disorder, rather than a system-wide illness.16,20 This discovery sparked years of additional research as investigators looked for ways to turn this new information into a practical tool for diagnosing MS. In 1959, Karcher et al discovered that a process known as agarose gel electrophoresis successfully separated key globulin proteins, revealing the distinctive oligoclonal banding pattern that is indicative of multiple sclerosis.21

Image of oligoclonal banding patterns: normal vs multiple sclerosis
Reproduced from Multiple Sclerosis Trust. Lumbar puncture. https://www.mstrust.org.uk/a-z/lumbar-puncture. Updated March 2018. Accessed September 28, 2019.

A New Addition to the McDonald Criteria

Since then, oligoclonal bands have come to be considered a major immunological hallmark used to support a diagnosis of MS.8,19,20 In 2017, experts added OCB testing to the McDonald criteria for diagnosing MS.5 The decision was based on numerous studies that found OCB can reliably predict if patients with clinically isolated syndrome (CIS) are at risk of a second attack. As of 2017, the updated McDonald criteria state that CSF-specific oligoclonal bands can be used to definitively diagnose MS in patients with typical CIS who have already met the MRI criteria for dissemination in space.5 In other words, OCB evidence can now be used in place of MRI evidence to demonstrate dissemination in time.

OCB Testing Is Strongly Recommended When5:

  1. MRI and clinical evidence do not fully support an MS diagnosis.
  2. Patients present with symptoms not typical to CIS (ie, progressive onset disease).
  3. Available evidence (imaging, clinical) includes key features uncommon to MS.
  4. The patient belongs to a population not commonly diagnosed with MS (children, elderly, nonwhite populations).

 

Of course, the sensitivity of OCB testing depends on the technique used by clinicians. The most sensitive technique available is agarose gel electrophoresis with isoelectric focusing and immunoblotting or immunofixation for IgG. As part of the process, it’s important to analyze both the patient’s CSF and blood to ensure that the oligoclonal bands are unique to the CSF—indicating a neuro-specific condition.5

The Prognostic Value of OCB

While OCB testing is now being embraced as an effective diagnostic tool, studies have shown it can also be used to help determine the prognosis of patients with MS.4,6-8 In a 2009 study of 200 patients with MS, Joseph et al found that patients who tested positive for OCBs experienced greater disability over time.6 In a separate 2012 study of 176 patients with relapsing-remitting MS, Rojas et al found similar results. Patients who were OCB+ were significantly more likely to convert to secondary progressive MS and were more likely to have a higher score on the Expanded Disability Status Scale (EDSS).7

More recently, a 2018 study found that the number of oligoclonal bands a patient has can be indicative of their long-term outcome. In an examination of 128 patients with multiple sclerosis, Perrone et al found that patients with 10 or more OCBs early in the course of the disease were likely to have significantly more relapses over time and were likely to experience more severe disease progression within 2 years of follow-up.4

Patients With Greater Number of OCBs May Have Greater Disease Activity (n=128)4

Study Metric<10 OCB≥10 OCB
Annualized clinical relapse rate<0.2≈0.7
Annualized radiographic relapse rate≈0.51.0
Number of new lesions48107

 

A Hidden Correlation: OCB and GM Pathology

As the importance of OCB testing becomes increasingly clear, there is emerging evidence that oligoclonal banding may also be associated with more severe Grey Matter pathology in patients with MS.8 In a 10-year observational, cross-sectional study (N=90), patients with MS who tested positive for OCBs at the start of the study had 2.7 times more cortical lesions compared with patients who had no OCBs (P<0.0001). At the same time, there was no significant difference in the number of White Matter lesions between the 2 groups. Of equal importance, researchers found that patients with OCBs at baseline experienced greater disability over time compared with the OCB– group. The disability reported included both physical and cognitive dysfunction, as measured by EDSS and by the brief repeatable battery of neuropsychological tests, which measured visuo-spatial learning, memory, attention, processing speed, and verbal fluency.8

2.7x

the number of cortical lesions in OCB+ vs OCB– patients8

“OCB at MS onset are associated with more severe GM pathology and with a more severe physical disability and cognitive impairment after 10 years.”
–Farina et al8

A Valuable Test for Managing Patients With MS

Decades of research have demonstrated that oligoclonal banding is a valuable tool for both diagnosing MS and for predicting long-term outcomes in patients with confirmed disease. Studies have shown that OCB testing has a 95% accuracy rate and can reliably predict whether a patient with CIS will advance to confirmed MS. The presence of OCBs in early disease can also help identify patients at greater risk of developing cortical lesions and of developing significant disability over time. Although the procedure can be expensive and somewhat invasive, examining cerebrospinal fluid for OCBs is a uniquely robust laboratory test that can provide major benefits to healthcare professionals who are managing patients with MS.

Register for More Information

To learn more about the role of Grey Matter in multiple sclerosis, please provide your contact information below.

*Required

Are You a Healthcare Professional?