By T N Ashok
NEW YORK: The doctor delivered what sounds like the best news in medicine. “Congratulations – you don’t have MS.” Christina Applegate says she was anything but pleased.
The Emmy-winning actress, 54, told listeners of her podcast MeSsy on Tuesday that the multiple sclerosis she disclosed in 2021, and became one of America’s most visible faces of, is not what is wrong with her. Her symptoms have not lifted. She still needs a wheelchair to reach her doctor’s examination room.
“Nothing magical happened,” she told co-host Jamie-Lynn Sigler, who has MS herself. Applegate has returned to the start, with no explanation for her condition, while doctors investigate how a diagnosis built on brain imaging and years of treatment came undone.
The verdict is uncomfortable. This was not a freak event. It is a documented failure of American medicine, studied for a decade and still unresolved.
The most cited work is a 2016 study in Neurology led by Andrew Solomon of the University of Vermont, with colleagues at four academic centres including the Mayo Clinic. Of 110 patients found to have been wrongly diagnosed with MS, 70 percent had received disease-modifying drugs, a third had carried the label for a decade or longer, and 31 percent suffered unnecessary harm. Thirteen percent had taken a drug that can cause a potentially fatal brain infection.
A later study of referrals to Cedars-Sinai and UCLA put misdiagnosis at 17 percent and 19 percent respectively, roughly one in five. A 2024 Swiss-led analysis in the Multiple Sclerosis Journal found 15 percent. These figures come from specialist referral centres, which see the hard cases, so they are not a national census. The order of magnitude, though, is not in dispute. A 2012 survey of 122 MS specialists found more than 95 percent had seen a misdiagnosed patient within the previous year.
The price is paid twice. Patients take drugs they do not need, with real infection risk, at a cost that survey puts at often $40,000 or more per patient per year, while the actual condition goes unnamed and untreated.
No single test confirms MS. Diagnosis rests on symptoms, examination and MRI, and each can mislead. Brian Weinshenker of Mayo Clinic notes that numbness and weakness appear in many conditions more common and less serious than MS, and that harmless MRI abnormalities are common in healthy people.
Solomon’s team named three culprits: treating symptoms atypical for MS as though they were MS, lacking objective evidence of a lesion behind an attack, and leaning too hard on MRI in patients with vague complaints. Migraine was the most common correct diagnosis in the Cedars-Sinai and UCLA data. Nor is this only a generalist’s error: neurologists with MS training made the original call in 24 percent of cases.
A system-wide margin of error. MS is one chapter in a larger book. A 2014 analysis in BMJ Quality & Safety estimated that 5 percent of US adults, about 12 million people, face an outpatient diagnostic error every year, roughly half with potential for harm.
The Institute of Medicine, now the National Academy of Medicine, concluded in 2015 that most Americans will receive a wrong or late diagnosis at least once. Its president, Victor Dzau, called the problem largely unappreciated.
The Agency for Healthcare Research and Quality, the federal body leading the response, set a goal of preventing a million diagnostic errors a year by 2025.
The Academy’s panel conceded that data on diagnostic error are sparse and that mistakes are often spotted only in retrospect. That is why no one can say precisely how many MS patients are living inside a wrong answer.
What a wrong label takes. Statistics miss what Applegate described. For five years she had an answer to why her days were hard, a medical community and a public role. She now says she feels she let people down, and has nothing to replace the explanation. Her symptoms are real whatever their cause; she stepped away from acting after Dead to Me wrapped in 2023, her illness by then dictating her days.
What the misdiagnosis took was not only time but certainty, and a treatment path aimed at the wrong target. Sigler says they have learned this is not rare. Applegate points to a high number of MS misdiagnosis, discovered only after years of infusions. A patient told she is free of a disease has not been told she is well.
The remedies are unglamorous. Apply the McDonald criteria strictly, and not to patients whose symptoms do not fit. Never diagnose on an MRI alone. Test for mimics: antibodies against aquaporin-4 and MOG help separate neuromyelitis optica disorders from MS, though MOG testing is not fully validated. Defer the diagnosis when the picture is murky; Weinshenker’s group says doctors can often wait when nothing urgent threatens the patient.
Seek a second opinion from an MS center before committing to years of treatment. In Solomon’s study, reviewers saw an earlier chance to catch the error in 72 percent of cases. Revisit the file when something looks odd: Applegate’s reversal began when cell testing produced curious results. Patients can help too; AHRQ built a Question Builder app to prepare questions before appointments.
Medicine will never reach zero error. Symptoms overlap and tests are imperfect. But a margin of error is a reason for humility, not an excuse. When a diagnosis carries a decade of powerful drugs and a person’s identity, the system should be built to doubt it: second reads, specialist review, scheduled reappraisal.
Applegate’s doctors deserve credit for looking again. The scandal is how often no one does, and how some specialists, a 2012 survey found, chose not to tell patients at all. (IPA Service)
