Review article
Analyses of cerebrospinal fluid in the diagnosis and monitoring of multiple sclerosis

https://doi.org/10.1016/j.jneuroim.2009.09.002Get rights and content

Abstract

The laboratory evaluation of cerebrospinal fluid (CSF) has been routinely employed as a diagnostic test in the diagnosis of neuroimmunological disorders such as multiple sclerosis (MS). Recently, CSF analyses in MS have garnered renewed interest as a tool for monitoring disease activity and prognosis. With the identification of patients that are very early in their disease course, namely patients with a radiologically isolated (RIS) or a clinically isolated syndrome (CIS), the true value of these evaluations has yet to be fully explored. Ultimately, the hope is that biomarkers within this compartment will be identified that will identify etiologic factors of MS and other inflammatory disorders of the central nervous system.

In this review we discuss the history of CSF diagnostic tests and the most recent methodological advances. We also outline the potentially important diagnostic role and possible limitations of these tests.

Section snippets

History and general considerations

In late nineteenth century, Heinrich Irenaϋs Quincke and Heinrich Georg Queckenstedt developed methods of sampling and studying cerebrospinal fluid (CSF) (Murray, 2005). CSF sampling was initially developed for therapeutic purposes in the treatment of hydrocephalus, but shortly became a very useful diagnostic test for infections and other disorders.

The first to report a CSF abnormality in multiple sclerosis (MS) was Hinton (1922), when he noticed that patients with MS and syphilis had an

Oligoclonal banding: current methodology

AGE and IEF are two methodologies currently employed for the detection of CSF OCBs. The sensitivity of AGE for the detection of OCBs in MS CSF varies from 47% to 77% (Luque and Jaffe, 2007a). Paired CSF and serum are electrophoresed on high-resolution agarose and stained for protein to identify unique CSF protein bands in the γ region. A positive test is considered 2 or more bands in the γ region of the CSF that do not appear in the serum. Unfortunately, considerable inconsistencies in

Oligoclonal bands in multiple sclerosis: roles in diagnosis, prognosis, and monitoring of disease activity

The diagnosis of MS is ultimately a clinical decision that does not require laboratory tests if neurologic dysfunction in time and space can be established, and alternative diagnoses excluded. However, CSF analysis is extremely helpful in patients with an atypical clinical presentation, age of onset, or magnetic resonance imaging (MRI) (Merra, 1984). It is also of paramount importance to exclude some infectious and inflammatory mimics (Herndon, 2006). For this particular purpose, CSF studies

Additional CSF measures in multiple sclerosis

The IgG index (CSF/serum IgG:CSF/serum albumin) is elevated (> 0.6) in about 70%–90% of MS patients but is rarely abnormal in OCBs-negative patients. Due to its relatively low sensitivity, the IgG index cannot replace testing for OCBs, but an isolated elevated IgG index should arouse clinical suspicion for demyelinating disease in the appropriate clinical context (Reiber et al., 1998, Tourtellotte et al., 1976, McLean et al., 1990). The IgG index, however, may have a value in therapeutic

The effect of pharmacotherapies on the presence of oligoclonal bands in patients with MS

There is currently unsufficient evidence that any of the approved pharmacotherapies for MS has a biologically relevant bioavailability in the CNS compartment. Furthermore, it is currently uncertain to what degree these agents have indirect effects on humoral immune responses within the brain and spinal cord. The immunomodulatory agent interferon beta has no apparent effect on the number of OCBs in the CSF (Confavreux et al., 1986, Rudick et al., 1999b). For glatiramer acetate, there is no data

CSF studies in patients with a clinically isolated syndrome

CSF parameters may play an important role in predicting the development of clinically definitive MS (CDMS) in patients with a clinically isolated syndrome (CIS), which may ultimately lead to earlier and more effective therapeutic interventions for these individuals. In the early 1980s, Poser et al. (1982) demonstrated that the presence of OCBs is positively correlated with development of CDMS in isolated myelitis. In a group of 52 patients with CIS, confirming the presence of OCBs by IEF was

Novel potential CSF biomarkers in MS

In clinical practice, only OCBs and IgG index are routinely utilized. Nevertheless, a very large number of markers are under investigation and may prove helpful in a variety of clinical settings. A list of potential CSF biomarkers is shown in Table 2 (Matsuda et al., 1995, Droogan et al., 1996, Mössner et al., 1996, McDonnell et al., 1998, Frigerio et al., 1998, Baraczka et al., 1999, Baraczka et al., 2001, Baraczka et al., 2003, McMillan et al., 2000, Rieckmann et al., 1998, Correale and

Summary

The role of CSF examination in MS diagnosis and the determination of prognosis are in constant flux. Currently, its main role is to support and rule-out the diagnosis of MS, and to exclude differential diagnoses. However, new technologies may expand to the role of paraclinical CSF testing in the future. It is conceivable that CSF biomarkers, alone or in addition with other surrogate disease markers on MRI, may help the clinician to predict disease progression from CIS to CDMS, and to monitor

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