Diagnosing primary progressive MS difficult, despite guidelines

Study finds 228 of 322 PPMS patients fully met 2017 McDonald criteria

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Diagnosing primary progressive multiple sclerosis (PPMS) can be challenging, with obstacles ranging from ruling out other disorders to differentiating between PPMS and other types of multiple sclerosis (MS).

These difficulties were highlighted in the study, “Real-world challenges in the diagnosis of primary progressive multiple sclerosis,” published in the European Journal of Neurology.

“Our data stress the need for a critical review of the patients prior medical history and possible confounding factors before making a diagnosis of PPMS,” the researchers wrote.

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Most people with MS initially develop relapsing-remitting disease (RRMS), which is marked by relapses where symptoms suddenly worsen, followed by periods of remission where symptoms ease or disappear entirely. A minority of MS patients will have PPMS, which is marked by symptoms that gradually worsen over time immediately from disease onset.

Guidelines used to diagnose MS are called the McDonald criteria, updated most recently in 2017. Under these criteria, a person can be diagnosed with PPMS if they experience continually worsening symptoms for at least a year, accompanied by MRI and laboratory findings that are characteristic of MS and tests to exclude other possible explanations.

Although getting an early and accurate MS diagnosis is a crucial goal of clinical care, correctly applying the diagnostic criteria for PPMS can be tricky.

Researchers in the Netherlands reviewed data on 322 people diagnosed with PPMS by a neurologist between 1974 and 2019 at two centers in the country. Their goal was to identify common issues in confirming an accurate diagnosis.

Based on the 2017 McDonald criteria, however, only 228 of these 322 patients met criteria for PPMS.

Using the 2010 version of the McDonald criteria, 240 met PPMS criteria. The researchers noted that the slightly higher rate with the older version was because the 2017 criteria included some more stringent requirements for interpreting lab tests.

“In our cohort of patients diagnosed with PPMS by their treating neurologist, in over one third of the patients we found that on critical review of the available data we could challenge the diagnosis of PPMS,” the researchers wrote.

Comorbidities and tracing progression to MS onset among difficulties

Among diagnosed patients who didn’t meet the McDonald criteria, there were 28 individuals with other co-occurring health problems (comorbidities) that may have unduly influenced the diagnosis, or other potential explanations for symptoms that weren’t conclusively ruled out before a PPMS diagnosis was made.

These findings highlight the importance of considering alternative explanations before diagnosing someone with MS, the researchers said.

They also identified 103 patients who had clinical signs consistent with progressive MS, but where it was not clear whether the progression started at disease onset.

Some of these patients had signs of earlier relapse activity that wasn’t accurately identified as MS. As such, it’s possible that these individuals would be more accurately classified as having a relapsing type of MS, rather than PPMS.

“The biggest challenge in the diagnosis of PPMS we encountered were patients without a definite progressive disease onset,” the researchers said.

“The common factor of these findings is that they illustrate the challenges in distinguishing relapsing from pure progressive MS,” they added. “And even though there are subgroups in both ends of the spectrum with truly relapsing and truly progressive disease course, it is likely that there is also a subgroup of patients in whom this differentiation is not so certain.”

These difficulties raise questions about how useful it is to differentiate between PPMS and relapsing-onset forms of MS, the scientists wrote. They proposed that, in the future, it may be more useful to have criteria that can be used to establish a diagnosis of MS regardless of the disease’s type.

“It could be argued that a single set of diagnostic criteria for any disease course of MS would simplify the diagnostic process,” the team wrote.

Among the 191 patients given a PPMS diagnosis without any better explanation, the researchers noted that only 118 had received a full diagnostic workup as outlined by the McDonald criteria. Among these patients with a full diagnostic workup, 83% met the 2017 McDonald criteria and 88% met the 2010 McDonald criteria.

“These findings show that a thorough and critical review, and sometimes reevaluation of the disease course is essential in a diagnosis of PPMS and that even in patients with a complete diagnostic work up the diagnosis can be challenging,” the researchers wrote.