Multiple Sclerosis (MS) is a chronic, unpredictable autoimmune disease of the central nervous system (CNS). The immune system attacks the protective myelin sheath surrounding nerve fibers, causing inflammation and damage. This damage disrupts the flow of information within the brain and body, leading to various neurological symptoms. To ensure consistent and timely diagnosis globally, neurologists rely on a standardized framework known as the McDonald Criteria.
The Purpose and Evolution of the Criteria
Standardized diagnostic guidelines were necessary to ensure uniformity in how MS is identified across medical centers and countries. Before the McDonald Criteria, diagnosing MS often took many years, requiring patients to experience multiple clinical attacks before a definite diagnosis could be made. This delay was a barrier to initiating timely treatment that could slow disease progression.
The McDonald Criteria, first introduced in 2001, marked a significant shift by incorporating Magnetic Resonance Imaging (MRI) findings into the diagnostic process, allowing for an earlier and more accurate diagnosis. These criteria have undergone several revisions, with updates in 2005, 2010, and most recently in 2017, reflecting advancements in imaging technology and a deeper understanding of MS pathology. Revisions aimed to increase diagnostic speed while maintaining high specificity, ensuring MS is diagnosed only when other conditions are ruled out. The 2017 revision introduced changes that allow for the diagnosis to be made at the time of a person’s first clinical event, significantly shortening the diagnostic timeline.
Core Diagnostic Principles: DIS and DIT
The McDonald Criteria rests on demonstrating that neurological damage is disseminated in both space and time. Evidence must show that the disease has affected multiple areas of the CNS and that these events have occurred at different points in time. Dissemination in Space (DIS) requires objective evidence of lesions in at least two distinct anatomical areas within the CNS.
MS lesions tend to cluster in specific CNS locations. Demonstrating DIS confirms the disease process is widespread, rather than localized to a single site. This requirement helps distinguish MS from other neurological conditions that may cause a single, isolated demyelination event.
The second principle is Dissemination in Time (DIT), requiring evidence that demyelination has occurred on more than one occasion. Since MS involves episodes of inflammation and repair, proving the disease process is ongoing or recurrent is necessary for a definitive diagnosis. DIT indicates that the neurological events represent the relapsing or progressive nature typical of MS.
Satisfying both DIS and DIT is paramount to confirming the diagnosis of MS in individuals presenting with an initial neurological event. The criteria provide a flexible set of rules for how these two principles can be fulfilled, combining clinical observation with advanced imaging and laboratory results.
Clinical and Imaging Evidence Required
The McDonald Criteria relies on gathering specific clinical, imaging, and laboratory evidence to confirm DIS and DIT. Clinical evidence begins with a neurological attack, defined as symptoms lasting at least 24 hours, occurring without fever or infection, and reflecting damage in a specific CNS location. MS can be diagnosed based purely on clinical attacks if a person has experienced two or more attacks and has objective clinical evidence of two or more lesions in different CNS sites.
Magnetic Resonance Imaging (MRI) plays a predominant role by providing visual evidence of lesions that satisfy DIS and DIT requirements. To meet the DIS criteria via MRI, the 2017 revisions state that a person must have one or more T2-hyperintense lesions in at least two of four characteristic CNS areas:
- The periventricular region (around the ventricles of the brain)
- The juxtacortical/cortical region (near or within the brain’s outer layer)
- The infratentorial region (brainstem and cerebellum)
- The spinal cord
MRI can also satisfy DIT without waiting for a second clinical attack. The criteria are met if a single MRI scan simultaneously shows both older (non-enhancing) and newer (enhancing, active inflammation) disease activity. DIT can also be confirmed if a follow-up MRI, performed at any time after the initial scan, reveals a new T2 or enhancing lesion compared to the baseline scan.
When clinical and MRI findings are insufficient to demonstrate DIT, ancillary tests become important. A lumbar puncture collects Cerebrospinal Fluid (CSF) to look for oligoclonal bands (OCBs), which are unique proteins representing an immune response confined to the CNS. The 2017 criteria allow CSF-specific OCBs to substitute for the DIT requirement in a person who has already met the DIS criteria. This offers an alternative pathway to a faster diagnosis, reducing the need for prolonged observation.
Applying the Criteria to Specific Syndromes
The McDonald Criteria provide tailored approaches for diagnosing MS in individuals presenting with specific initial neurological events. One such presentation is Clinically Isolated Syndrome (CIS), a first episode of neurological symptoms caused by demyelination that does not yet meet the full criteria for MS. A person with CIS may present with symptoms like optic neuritis or an isolated spinal cord event.
The criteria are applied to a person with CIS to determine their risk of converting to definite MS. If the initial MRI scan in a person with CIS already shows evidence of DIS, and subsequent testing reveals DIT (either through a new lesion on follow-up MRI or the presence of CSF OCBs), a diagnosis of MS can be confirmed immediately. This accelerated diagnostic pathway allows for earlier treatment initiation.
The criteria are also adapted for the diagnosis of Primary Progressive MS (PPMS), a form of the disease characterized by a gradual, steady worsening of neurological function from the onset, without distinct relapses. Since PPMS lacks the clear-cut attacks necessary to demonstrate DIT, the diagnostic requirements shift. For a PPMS diagnosis, a person must show at least one year of continuous disease progression, combined with evidence of DIS in the CNS.
The DIS evidence for PPMS requires one or more T2 lesions in the characteristic brain regions (periventricular, juxtacortical, or infratentorial) or two or more T2 lesions in the spinal cord. The criteria for PPMS often rely on CSF-specific OCBs to support the diagnosis, since the clinical course lacks the temporal separation of events seen in relapsing MS. The flexibility of the McDonald Criteria ensures the diagnostic standard remains high for all forms of the disease.