Multiple sclerosis diagnostic study of choice

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Fahimeh Shojaei, M.D.

## Overview

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There is no single diagnostic study of choice for the diagnosis of multiple sclerosis, but multiple sclerosis can be diagnosed based on clinical presentation, MRI findings, and CSF analysis. Sequence of diagnostic studies are history and physical examination, imaging, and CSF analysis. The findings are cerebral plaques which are demyelinating areas on MRI and an elevated concentration of CSF oligoclonal bands. The diagnostic criteria for multiple sclerosis is McDonald criteria.

## Diagnostic Study of Choice

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### Study of choice

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There is no single diagnostic study of choice for the diagnosis of multiple sclerosis, but multiple sclerosis can be diagnosed based on clinical presentation, MRI findings, and CSF analysis.

Investigations:

* Among the patients who present with clinical signs of multiple sclerosis, the CSF analysis is the most specific test for the diagnosis.
* Among the patients who present with clinical signs of multiple sclerosis, the MRI is the most sensitive test for diagnosis.

##### Diagnostic results

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The following findings are confirmatory for multiple sclerosis:

* Cerebral plaques which are demyelinating areas on MRI.[1]
* An elevated concentration of CSF oligoclonal bands.[2][3][4]

##### Sequence of Diagnostic Studies

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* History and physical examination
* Imaging
* CSF analysis

### McDonald criteria

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The diagnostic criteria for multiple sclerosis is McDonald criteria.[5][6]

Clinical presentation | Additional Data Needed

|

* 2 or more attacks (relapses)
* 2 or more objective clinical lesions

* None; clinical evidence will suffice (additional evidence desirable but must be consistent with MS)

* 2 or more attacks

* 1 objective clinical lesion

| Dissemination in space, demonstrated by:

* MRI
* Further clinical attack involving different site
* Presence of 1 or more T2 lesions in at least 2 of 4 of the following areas of the CNS: Periventricular, Juxtacortical, Infratentorial, or spinal cord

New criteria: Dissemination in Space (DIS) can be demonstrated by the .

* 1 attack

* 2 or more objective clinical lesions

| Dissemination in time (DIT), demonstrated by:

* MRI
* Second clinical attack

New criteria: No longer a need to have separate MRIs run; Dissemination in time, demonstrated by: Simultaneous presence of asymptomatic gadolinium-enhancing

and nonenhancing lesions at any time; or A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan; or Await a second clinical attack. [This allows for quicker diagnosis without sacrificing specificity, while improving sensitivity]

* 1 attack

* 1 objective clinical lesion (clinically isolated syndrome)

| New criteria: Dissemination in space and time, demonstrated by:

* For DIS: 1 or more T2 lesion in at least 2 of 4 MS-typical regions of the CNS (periventricular, juxtacortical, infratentorial, or spinal cord); or Await a second clinical attack implicating a different CNS site; and For DIT: Simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions at any time; or A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan; or Await a second clinical attack.

* Insidious neurological progression suggestive of MS (primary progressive MS)

| New criteria: One year of disease progression (retrospectively or prospectively determined) and two or three of the following:

* Evidence for DIS in the brain based on 1 or more T2 lesions in the MS-characteristic (periventricular, juxtacortical, or infratentorial) regions

* Evidence for DIS in the spinal cord based on 2 or more T2 lesions in the cord

## References

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1. ↑ Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L (January 1998). "Axonal transection in the lesions of multiple sclerosis". N. Engl. J. Med. 338 (5): 278–85. doi:10.1056/NEJM199801293380502. PMID 9445407.
2. ↑ McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS (July 2001). "Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis". Ann. Neurol. 50 (1): 121–7. PMID 11456302.
3. ↑ Dobson R, Ramagopalan S, Davis A, Giovannoni G (August 2013). "Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude". J. Neurol. Neurosurg. Psychiatry. 84 (8): 909–14. doi:10.1136/jnnp-2012-304695. PMID 23431079.
4. ↑ McLean BN, Luxton RW, Thompson EJ (October 1990). "A study of immunoglobulin G in the cerebrospinal fluid of 1007 patients with suspected neurological disease using isoelectric focusing and the Log IgG-Index. A comparison and diagnostic applications". Brain. 113 ( Pt 5): 1269–89. PMID 2245296.
5. ↑ Gobbin F, Zanoni M, Marangi A, Orlandi R, Crestani L, Benedetti MD, Gajofatto A (January 2019). "2017 McDonald criteria for multiple sclerosis: Earlier diagnosis with reduced specificity?". Mult Scler Relat Disord. 29: 23–25. doi:10.1016/j.msard.2019.01.008. PMID 30658260.
6. ↑ McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS (July 2001). "Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis". Ann. Neurol. 50 (1): 121–7. PMID 11456302.

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