The McDonald criteria are an internationally recognized set of standards that neurologists use to diagnose Multiple Sclerosis (MS). First established in 2001 by a global panel of experts, these guidelines provide a structured, evidence-based framework for a complex diagnostic process. The purpose of the criteria is to ensure an MS diagnosis is made with accuracy and consistency across different clinical settings.
Diagnosing MS is challenging because its symptoms can vary widely and mimic other neurological conditions. The McDonald criteria address this by outlining specific requirements that combine clinical observations, imaging data, and laboratory tests. This systematic approach helps clinicians confirm MS-related damage in the central nervous system, which includes the brain, spinal cord, and optic nerves. By standardizing the process, the criteria enable an earlier, more reliable diagnosis and allow for prompt treatment.
Dissemination in Space and Time
The McDonald criteria are built on two principles: dissemination in space (DIS) and dissemination in time (DIT). These concepts establish that MS damage is not a one-time event or confined to a single area. For a definitive MS diagnosis, a neurologist must find evidence of both DIS and DIT, which helps distinguish MS from other conditions that might cause a single neurological episode.
Dissemination in space refers to evidence of MS-related damage, known as lesions, in at least two separate locations within the central nervous system. The 2017 criteria specify four key areas: periventricular, cortical or juxtacortical, infratentorial, and the spinal cord. To meet the DIS requirement, a person must show lesions in at least two of these four regions.
Dissemination in time confirms the disease process is ongoing and that lesions have developed at different points. This can be demonstrated in a few ways, with the most direct evidence being a second clinical attack. Alternatively, a follow-up Magnetic Resonance Imaging (MRI) scan can show a new lesion that was not present on an earlier scan.
The criteria also allow for DIT to be established from a single MRI scan under specific circumstances. If a scan reveals the simultaneous presence of an older, non-enhancing lesion and a newer, actively inflamed lesion that enhances with a contrast agent, this can satisfy the DIT requirement. The presence of specific inflammatory proteins in the cerebrospinal fluid can also substitute for demonstrating DIT.
Gathering Diagnostic Evidence
Magnetic Resonance Imaging (MRI) is central to the process because it reveals MS lesions, allowing for detailed visualization of the brain and spinal cord. T2-weighted MRI images are particularly effective at showing both old and new lesions, which appear as bright spots. To determine if a lesion is new and actively inflamed, a gadolinium-based contrast agent is administered intravenously. This contrast agent leaks into areas of active inflammation, causing these lesions to appear bright on T1-weighted images.
A clinical attack, or relapse, provides direct evidence of the MS disease process. A clinical attack is defined as an episode of new or worsening neurological symptoms—such as numbness, weakness, or vision problems—that lasts for at least 24 hours and is not caused by fever or infection. Documented attacks affecting different parts of the central nervous system at different times can fulfill the requirements for both DIS and DIT.
Another diagnostic tool is the analysis of cerebrospinal fluid (CSF), which is collected through a lumbar puncture. The primary goal of CSF analysis is to detect the presence of oligoclonal bands (OCBs), which are specific inflammatory proteins. The presence of OCBs in the CSF that are not found in the blood indicates inflammation confined to the central nervous system, a hallmark of MS.
Evolution of the Diagnostic Criteria
The McDonald criteria have evolved since their introduction in 2001, with revisions in 2005, 2010, and 2017, and further updates proposed in 2024. This evolution reflects advances in medical technology and a growing understanding of MS. The goal of these updates is to make the diagnostic process faster and more accurate.
Before the McDonald criteria, diagnosing MS often required waiting for a second clinical attack, which could delay treatment. The 2001 criteria formally incorporated MRI findings, allowing for a diagnosis to be made even after a single clinical event, known as a Clinically Isolated Syndrome (CIS), provided there was sufficient MRI evidence. Subsequent revisions have further streamlined this process.
The 2010 revision simplified the MRI requirements for DIS and DIT. The 2017 update incorporated the presence of oligoclonal bands as a substitute for DIT in certain cases, which allows for a much sooner diagnosis and earlier intervention. The proposed 2024 revisions continue this trend, suggesting the inclusion of new MRI markers and counting the optic nerve as a fifth location for DIS.
Diagnosing Different Types of MS
The McDonald criteria are adapted to diagnose different clinical courses of MS. The most common form is Relapsing-Remitting MS (RRMS), which is characterized by clear episodes of clinical attacks followed by periods of recovery. Diagnosing RRMS follows the standard application of the criteria, requiring evidence of damage spread out in both space and time.
For RRMS, a diagnosis is confirmed if a patient has at least two clinical attacks in different CNS areas. If there has only been one attack, additional proof of DIT is required, such as a new MRI lesion or the presence of oligoclonal bands.
Diagnosing Primary Progressive MS (PPMS) is different, as it involves a steady worsening of neurological function without distinct relapses. The McDonald criteria provide a separate pathway for diagnosing PPMS, requiring at least one year of continuous disease progression. This can be identified either in real-time or by reviewing the patient’s history.
In addition to one year of progression, the PPMS criteria require further supporting evidence. A patient must meet at least two of the following three conditions:
- The presence of one or more MS-characteristic T2 lesions in the brain.
- Two or more T2 lesions in the spinal cord.
- The presence of oligoclonal bands in the cerebrospinal fluid.