MHH researchers are investigating the revised McDonald criteria for diagnosing multiple sclerosis.
Neurologists Dr. Felix Konen (left) and Prof. Dr. Thomas Skripuletz are examining an antibody pattern from cerebrospinal fluid and blood serum samples, which is important for diagnosing MS. Copyright: Karin Kaiser/MHH
Multiple sclerosis (MS) is the most common chronic autoimmune disease of the central nervous system. An early and accurate diagnosis is crucial for improving the effectiveness of treatment and reducing nerve damage. To standardize and expedite diagnoses, the so-called McDonald criteria were introduced in 2001 and have since been revised several times, most recently in 2024. They combine clinical findings—such as visual disturbances, sensory disturbances, and unsteady gait—with results from magnetic resonance imaging (MRI), which reveals changes in the brain and spinal cord, as well as inflammatory markers in the cerebrospinal fluid. In 2024, the diagnostic criteria were revised and expanded. Among the new additions are changes in the optic nerve. In addition, a diagnosis can now be made based solely on the MRI image, without the need for clinical symptoms to be present. In a study, a research team from the Clinical Department of Neurology with Clinical Neurophysiology at Hannover Medical School (MHH) has now compared the old and new diagnostic criteria. The result: The newly added diagnostic criteria led to the early identification of more people with MS who would previously have gone undiagnosed. The findings have been published in the journal “eClinicalMedicine – The Lancet Discovery Science.”
Lesions in the optic nerve are also important
“Our results show that the McDonald criteria, revised in 2024, significantly increase the proportion of first-time diagnoses—by nearly ten percentage points,” says study leader Prof. Dr. Thomas Skripuletz, a senior physician at the Clinical Department. Cases that were previously unclear can now be classified more quickly and reliably. Most of the additional diagnoses resulted from including the optic nerve as the fifth site for inflammatory foci, known in medical terminology as lesions. Until now, MRI imaging had focused on lesions in four affected areas: directly around the brain ventricles filled with cerebrospinal fluid, in the cerebral cortex, in the brainstem or cerebellum, and in the spinal cord. “Including the optic nerve is important because it is also damaged by inflammation of the central nervous system,” the neurologist emphasizes. Early signs of MS therefore often include blurred vision, pain when moving the eyes, and impaired color perception. “In our study, taking optic nerve involvement into account was the main reason for the earlier diagnosis.”
Diagnosis possible before symptoms appear
Evidence of optic nerve inflammation can be detected using MRI, as well as optical coherence tomography (OCT) and measurements of so-called visual evoked potentials (VEP). The latter test the conductivity and functionality of the visual pathway from the retina to the brain. It is also important to note that, for the first time, patients with radiologically isolated syndrome (RIS) could be included in MS diagnostics. “Sometimes an MRI is performed—for example, after an accident—and it reveals changes that are typical of MS,” explains Professor Skripuletz. However, without clinical symptoms, MS was considered “unconfirmed.” “Thanks to the new criteria, we can now make the diagnosis based on the MRI image earlier, before symptoms appear.”
Routine clinical diagnostic tools are sufficient
The McDonald criteria, revised in 2024, also include new MRI markers in the diagnostic catalog. However, these were not considered in the study because the researchers used only conventional diagnostic tools available in routine clinical practice. Assessing these new MRI markers requires modern imaging techniques as well as a high level of neuroradiological expertise. Furthermore, the added benefit of this specialized imaging is limited to only a small group of people with MS. “The new MRI markers are promising, but many patients can already be diagnosed early using established MRI, VEP, and cerebrospinal fluid diagnostics,” says Dr. Felix Konen, a neurologist at the Clinical Department and the study’s first author.
CSF diagnostics play a central role
A new cerebrospinal fluid (CSF) biomarker indicating inflammation in the central nervous system was incorporated into the diagnostic components. The so-called kappa index indicates MS with a reliability similar to that of oligoclonal bands. With oligoclonal bands, the antibody pattern in CSF and blood serum samples is examined and directly compared. The new marker, however, can be measured fully automatically and more quickly in the laboratory. “Our study demonstrates that the McDonald criteria, revised in 2024, significantly increase the proportion of patients diagnosed with MS as early as the initial examination—even when using conventional diagnostic tools,” emphasizes Professor Skripuletz. “Our findings support a pragmatic implementation of the revised criteria in clinical practice and underscore the central role of cerebrospinal fluid diagnostics. With the inclusion of the kappa index, cerebrospinal fluid diagnostics gains even greater importance and can contribute to faster and more standardized diagnosis. Without cerebrospinal fluid diagnostics, a quarter of the patients could not have been diagnosed according to the McDonald criteria revised in 2024.”
Further studies should now evaluate the additional potential benefits of the new MRI markers and clarify for which people with MS the additional diagnostic benefit justifies the necessary personnel and technical resources.
Keyword: multiple sclerosis
Multiple sclerosis (MS) is the most common chronic autoimmune disease of the central nervous system, affecting the brain and spinal cord. In this condition, misdirected immune cells attack the protective sheaths of nerve fibers. As a result, inflammatory lesions develop, nerve impulses are transmitted less effectively, and the nerves are damaged. An estimated 280,000 people in Germany live with MS. More than 15,000 new cases are diagnosed each year. Young adults are predominantly affected. The course of the disease varies from person to person. Symptoms and limitations in daily life can vary in severity. The disease can also progress largely unnoticed. Early diagnosis is therefore all the more important for controlling the disease and limiting long-term damage to the nervous system.
The original study, “Applying the 2024-revised McDonald criteria for multiple sclerosis using conventional diagnostic tools: a single-center prospective cohort study in Germany,” can be found here.
Text: Kirsten Pötzke