she said on a podcast that she felt she was "back at square one, where I don't know what's going on with me."
Applegate's case is not totally unique, although MS diagnosis has improved over the years. Studies offer different estimates of how frequently MS is misdiagnosed, with rates ranging from 5% to over 40%, depending on the patient population and clinical setting. There is also some degree of underdiagnosis — cases in which people with MS aren't flagged as having the disease.
So, how difficult is MS to identify, and what does that mean for patients? Live Science spoke with experts about the current state of MS diagnostics and the improvements that may be coming in the future.
"It's also really important that doctors and patients be aware that it's not inappropriate to revisit a diagnosis — to make sure it's right," Dr. Ari Green, chief of the Division of Neuroimmunology and Glial Biology at the University of California, San Francisco, told Live Science.
The importance of early diagnosis
MS is an autoimmune disorder in which the immune system attacks the central nervous system, meaning the brain and spinal cord. These attacks harm neurons directly and also take aim at myelin — a fatty, insulating substance that coats neurons' outgoing wires and helps them send signals efficiently.
This damage leads to distinctive scarring in nerve tissue and causes a range of symptoms, including vision problems, muscle weakness, tingling sensations, dizziness and bladder control issues. Patients with untreated and advanced MS can lose the ability to walk and stand or, in some cases, develop partial or complete paralysis.
You're trying to be as proactive as possible with this.
Dr. Yohance Allette, a neuroimmunologist and researcher at Penn State Health
These severe outcomes are becoming rarer as treatments have improved significantly, Green said. Current treatments keep immune attacks at bay and thus prevent further nerve damage.
"It's moved from people ending up with severe, profound disability at 10 or 20 years of disease, and now it's at like 30 or 40 years of disease, they have modest disability," Green told Live Science. The disease most often emerges between age 20 and 40, although it can occur in any age group. Importantly, Green said, "the earlier people initiate treatment who have MS, the better they do over the long term."
For that reason, it's important to reach an MS diagnosis efficiently, so that patients can start that critical treatment, said Dr. Yohance Allette, a neuroimmunologist and researcher at Penn State Health. "You're trying to be as proactive as possible with this."
"A diagnosis of exclusion"
However, there is no single, surefire test that can reliably show that a person has MS. "With MS, it comes down to the keyword 'criteria," Allette said.
MS experts have compiled a list of criteria, which are updated periodically, that reflect how the features of MS show up in lab tests; brain, optic nerve and spinal cord scans; and patients' symptoms. (Green was among the dozens of experts involved in the latest update, which was conducted in 2024 and published in 2025.)
So, what does diagnosis look like for a patient today? The first step is to recognize symptoms that might point to MS.
Those early symptoms — such as issues with balance, vision or bowel control — vary significantly from person to person and may not immediately raise red flags that the patient has a neurological problem, Green said. The way those symptoms emerge can be a clue, though; typically, MS symptoms worsen over the course of a day or a few days and then dissipate, he noted.
Once concerning symptoms are flagged, MRIs of the brain and spinal cord are taken. The scans may reveal evidence of myelin damage, and neurologists note the shape, size and location of those lesions. Damage often appears near blood vessels, since that's where immune cells access the brain, Green noted.
Other conditions — like migraine, uncontrolled diabetes or vascular disease — can also come with some myelin damage, so it's key to look for specific patterns related to MS. Neurologists who specialize in MS are practiced at this task, while doctors in other neurological specialties may not know how to distinguish MS-related myelin damage from that caused by other conditions, Allette and Green both noted.
Myelin (yellow) helps neurons send messages efficiently. In MS, the immune system attacks myelin, causing it to break down. (Image credit: koto_feja via Getty Images)MRIs of the optic nerves can also show MS-related damage, and these scans are emphasized in the latest diagnostic criteria, Allette noted. Electrophysiologic tests, which assess the function of nerves, are also "super important because they tell you something totally different than just seeing a lesion on MRI," Green said. Further signs of MS can be found via spinal taps, which sample the fluid around the brain and spinal cord that may carry proteins and inflammatory cells related to MS.
In addition to collecting these clues, doctors must rule out diseases that look similar to MS. These include neuromyelitis optica and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) — two other autoimmune conditions that affect the central nervous system. Both these diseases are associated with distinctive, rogue immune proteins, called autoantibodies, that latch onto various parts of the nervous system; those specific antibodies are not seen in MS.
Other conditions — such as the inflammatory disease lupus and neuromuscular disease myasthenia gravis — can sometimes look like MS at first glance, as well. Some of these "MS mimics" can be ruled out with data from spinal taps or antibody tests, while others require a more laborious battery of assessments.
"Ultimately, it's a diagnosis of exclusion," Allette said. "There are things that you can rule out quickly," while others take time to investigate thoroughly.
Conditions like MOGAD and neurosarcoidosis, an inflammatory condition sometimes mistaken for MS, can actually be worsened by MS medications, Green noted. So if a patient's MS flare-ups worsen after they start a treatment, that could hint that something else is the culprit, he said. But because there may be long gaps between flare-ups, doctors may need to track a patient for some time before their worsening becomes apparent.
Gaps to fill?
The updated diagnostic criteria for MS include new guidelines for how to examine brain MRIs. These criteria could likely be improved even more in future, Green noted. (Image credit: Douglas Sacha via Getty Images)Given all the tools available, a patient can be reasonably confident in their MS diagnosis, Green said.
"In general, there's a fair amount of diagnostic confidence that comes with MS diagnosis today," he said. However, that confidence is highest when the tools are in the hands of a specialist who is following the most up-to-date criteria, he noted. The test results require interpretation, and that's one place where uncertainty can creep in.
Regarding Applegate's circumstances, "to speak bluntly, I think the case came as a bit of a shock because we always expect that part of society to have quick access [to high-quality medical care]," Allette said. For some patients, the road to accessing specialty MS care can be long, which can result in missteps, and even misdiagnoses, along the way. Applegate went five years with an incorrect diagnosis, but "would that have been seven or eight years for somebody who doesn't have that access?" Allette speculated.
Without knowing the details of Applegate's case, Allette and Green said it would be difficult to speculate on what resulted in her misdiagnosis. (Applegate mentioned that her brain scans had been reassessed with a "new technology," but didn't go into specifics.)
Looking toward the future of MS diagnostics, Green and Allette think emerging proteomic tests hold a lot of promise. Such tests generate a profile of the proteins and smaller fragments, called peptides, in a patient's blood or cerebrospinal fluid. They can be designed to look for proteins involved in driving the underlying immune attacks, as well as signs of nerve damage that MS wrecks, they explained.
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These in-depth, protein analyses could help paint a more comprehensive picture of MS, which could ultimately help scientists "look at that whole system in concert" to reach a strong diagnosis, Allette said.
No proteomics-based diagnostic tests for MS have been approved yet, Green clarified. And even with those upcoming advances, Green doubts there will ever be a simple, one-time test that can determine a patient has MS. "I think that's probably unlikely, that it would ever be that straightforward," he said.
He does think that, in time, scientists could pare down the number of tests required to reach a diagnosis, but he argued that the clinical evaluation conducted by a neurologist will likely remain crucial. "I'm doubtful that there's going to be a test that will fully replace that," he said, "at least in the foreseeable future."
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'> Christina Applegate misdiagnosis: Why can MS be difficult to diagnose?
Other commenters echoed this sentiment. "It will never happen as some cheap alternative to electric or petrol driven vehicles," one person responded. "Gravity is master on this planet so to rise above that and be floating or propelled around on some sort of air current, Nah! I cannot imagine the damage that will take place in any livable area, towns, suburbs, cities, parks, etc, etc., that list is endless. And imagine the protests should a general public be allowed to dive and fly above any or all livable areas."
Not everyone was as adverse, with another commenter remarking on how far Tesla's technological development has come. "The flying roadster is a statement of what Mr. Musk can do with technology more than anything else. In the same way he can make the Roadster fly, be sure that the technology designed into the Tesla Y, the Cybercab or the Starship are at the very frontier of science. Mr Musk has singlehanded revolutionized the car industry and space travel in less than 20 years (the first Tesla car was sold in 2008). No small feat."
Do you agree or disagree with our readers? Tell us your thoughts in the comments.
'> 'Most people can't handle driving in 2 dimensions let alone 3': Readers respond to our poll about flying cars However, in its current form, the same AI technologies that add watermarks can also strip them away, other experts warned.
New ways to hide watermarks
The unveiling of the AI program AlphaFold in 2020 was a milestone in protein engineering. The tool, which won Demis Hassabis, John Jumper and David Baker the Nobel Prize in Chemistry in 2024, can reveal the 3D structure of a protein from the sequence of its building blocks, called amino acids. Proteins fold like origami, adopting 3D shapes that dictate their function.
However, AlphaFold's technology also opened the door to generating brand-new proteins that could be used to create biothreats, including viral proteins that can evade our immune systems and existing vaccines.
"Anything that can be used for good can be used for bad," said George Rose, professor emeritus of biophysics at Johns Hopkins University.
Current screening tools identify novel dangerous or restricted molecules by seeing how similar their amino acid sequences are to those of recognized threats. But the problem is that AI could come up with proteins that don't look like anything we've ever seen. That's what the new watermarking technique aims to solve.
The DeepMind team has framed the watermarking effort as a "family" of related techniques they call SynthIDBio. The first member of this family is SynthIDBio-sequence, which encodes watermarks into the amino acid sequences of proteins created by a program called ProteinMPNN.
The 3D shape of a protein is largely determined by its amino acid sequence, or the order of its building blocks. In cells, these blocks are assembled by ribosomes (pictured). (Image credit: STEVEN MCDOWELL/SCIENCE PHOTO LIBRARY via Getty Images)When users tell ProteinMPNN the desired 3D shape for their protein, it chooses amino acid options that ultimately fold into that shape. SynthIDBio-sequence subtly influences how the program chooses each amino acid according to a secret watermarking "key." Once the sequence is generated, anyone who knows the hidden code can assess how likely the sequence is to have been created under the key's bias. In their recent study, the DeepMind team showed that proteins built with this watermark could still bind to their targets as well as non-watermarked proteins.
A sister technique, called SynthIDBio-structure, instead embeds a watermark directly into the protein's structure. It does this by altering the function of AlphaFold 3, DeepMind's flagship protein prediction algorithm.
When AlphaFold predicts a structure, SynthIDBio-structure gives it a side mission: The AI must make minuscule tweaks to how the atoms in the protein are arranged. These tweaks can be picked up by a detector later, and they're small enough that they don't look like obvious distortion.
In a test, these two systems created hidden watermarks that could be detected with incredible accuracy, flagging more than 99% of watermarked proteins and correctly ignoring 99.9% of non-watermarked proteins.
How to bypass a protein watermark
Live Science spoke to several experts who agreed that SynthIDBio was an impressive technical feat. However, they said it wasn't ready for widespread implementation yet.
The two techniques are "effective but brittle," Bruce Wittmann, a principal applied scientist at Microsoft, told Live Science in an email. That's because, as the DeepMind team also notes in their paper, the watermarks can be easily removed.
I imagine it would be very difficult to ensure the regulations were being followed.
Bruce Wittmann, a principal applied scientist at Microsoft
"For sequences, watermarks can be removed by 'resequencing' — effectively, altering the protein amino acid sequence such that the watermark is no longer detectable," Wittmann said. "For structures, watermarks can be removed by adding noise to or otherwise modifying the spatial coordinates of the structure." Screening tools wouldn't be able to detect if a watermark had been removed from a protein.
Experts are also skeptical that watermarking would provide a long-term solution for biosecurity.
An indelible watermark could identify who originally made a nefarious protein, or identify when a user was accessing a protein generation software without permission. This might deter some criminals, but terrorists looking to create a novel protein for a biological weapon would be less likely to care about being identified after a successful attack, said Max Brackmann, a chemical, biological, radiological, and nuclear arms expert at the Spiez Laboratory in Switzerland.
Additionally, the vast majority of software for protein prediction and generation is open-source, meaning much of the code is freely available to use and modify. That makes it far harder to bake watermarking into these programs. Wittmann warned that the field would have to shift toward closed-source models before watermarks could become an industry standard.
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He added that watermarking could act as one layer of a biosecurity defense shield, rather than offering standalone protection. Top-down regulation would be challenging to enforce. "I imagine it would be very difficult to ensure the regulations were being followed," he said.
Rose was even blunter about regulating the use of generative proteins.
"I'm convinced it won't work," he said. "Once there's a sweet technology that does something, government regulation to keep it under wraps has never been really successful."
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'> Scientists can now 'watermark' AI-generated proteins to deter bioweapon creation. But will it really work? briefly feared that he and his crew would never return home from their trip around the moon after overshooting their turn-back point.
Commander Reid Wiseman and his three crewmates were supposed to reach 219,667 nautical miles (252,788 standard miles, or 406,823 kilometers) — farther than any humans have ever traveled from their home planet — before turning back toward Earth on the sixth day of their 10-day mission to the moon.
But the odometer on the Integrity spacecraft continued to tick upward as they shot past their intended point of return, leading the astronaut to fear that something had gone terribly wrong, he told an audience here at the Starmus VIII festival earlier this week. (This semi-annual event is held to celebrate achievements in science, exploration, and creativity.)
"Mission control in Houston had told us our maximum distance would be 219,667 nautical miles and that was the furthest we were supposed to be from Earth," Wiseman said. "I was watching this number, and I saw it hit 219,667, and I thought, 'Great, this is the farthest we will be from Earth, and the next number I will see will be 219,666 — we'll be going home.' But about three minutes later, I didn't see 219,666; I saw 219,668. It went up. I was like. 'Huh? That's weird.'
Artemis II astronauts Jeremy Hansen, Victor Glover and Reid Wiseman were presented with the Stephen Hawking Medal for Science Communication at the Starmus VIII festival in Tenerife, Spain, on Oct. 17. (Image credit: Max Alexander/Starmus)"And then about three minutes later, it goes to 219,669, and that was the moment that I felt real fear because I thought we had just gone too far — we're never going to come home — and so I was very scared," he added.
Then, at last, he saw the counter start to drop. Meanwhile, NASA astronauts Victor Glover and Christina Koch were at the window, doing science observations of the moon, and Canadian Space Agency astronaut Jeremy Hansen was sending reports back to mission control — so Wiseman's moment of terror went unnoticed.
When Wiseman saw the odometer click back to 219,668 nautical miles, he said, "We're going home," and the crew let out a cheer. "I knew there was a good chance we might make it," he added.
In an interview with Live Science's sister publication The Week Junior Science+Nature, Wiseman paid tribute to NASA's Earth-based teams for the ultimate success of the mission.
"Getting home safely is a testament to the engineering rigor and the flight control teams back here on planet Earth, who put this rocket together and then who controlled it as we went out to the moon and came back. Those are the true heroes of this mission. They have real courage."
The Artemis II mission launched from NASA's Kennedy Space Center in Florida on April 1. It was the first crewed flight of the Orion space capsule and the first crewed mission to travel to the moon since Apollo 17 in 1972, taking nearly 10 days to fly around the lunar far side and return to Earth.
Nearly every moment of the crew's activities in the Orion capsule was livestreamed to the world, garnering massive public interest in the mission. The Artemis II crewmembers were awarded the Stephen Hawking Medal for Science Communication at the Starmus VIII festival.
Are you a NASA nerd? See how well you score on our Artemis quiz to find out!
'> 'We're never going to come home': Artemis II commander recalls the most terrifying moment of his 10-day trip around the moon
To understand how crows make decisions using cues in their environments, the researchers trained two carrion crows to complete a visual task on a touchscreen. The birds watched a cloud of white dots moving against a black background. Some dots moved to the left or right while others moved randomly. The crows had to determine the predominant direction of the dots' movement and peck the corresponding target on the screen to earn a mealworm reward.
By changing the proportion of dots moving together, the researchers could make the decision easier or harder for the crow. When most dots moved in the same direction, the answer was fairly obvious for the birds. But when only a small percentage moved together, the birds had weaker visual evidence to base their decisions on.
One of the carrion crows used in the study completes a decision-making task. (Image credit: Andreas Nieder)The crows reached nearly 100% accuracy when many dots were involved and the motion was clear. But even when just 3% of the dots moved in concert, both birds performed significantly better than just guessing, getting the answer right 50% of the time.
The birds maintained high accuracy in different rounds of the experiment, suggesting they were not sacrificing judgement for quickness.
The study did not directly compare crows to humans and monkeys performing the exact same task. However, previous studies suggest that humans and monkeys take roughly twice as long on comparable, self-paced visual motion tasks.
What happens inside the crow brain?
To understand how the birds reached their decisions so quickly, the researchers recorded activity from 248 neurons in the nidopallium caudolaterale (NCL) — a region of the bird brain that's considered functionally comparable to the prefrontal cortex in humans and primates. Birds lack the layered cerebral cortex found in mammalian brains, but the NCL performs similarly advanced functions.
In primates, neurons accumulate sensory information and their activity increases until it hits a critical threshold and the brain reaches a decision. The new findings suggest that crows use a comparable process, the researchers concluded.
"The bigger implication is that a brain does not need a mammalian neocortex to perform sophisticated computations," Nieder said.
The team could use neural activity to predict the crows' eventual choice "as early as 70 milliseconds after" the dots appeared, Nieder said. That was roughly 170 milliseconds before the crows' behavioral responses, meaning their pecks at the screen.
The speediness of the crows' decision-making may reflect the demands of the birds' daily lives.
"Flight places enormous demands on visual processing and sensorimotor [sensation and movement] coordination," Nieder said. "Birds must navigate three-dimensional environments, avoid obstacles, and react quickly to moving objects. Finding food and capturing prey can also require rapid, precise decisions. These pressures may have favoured fast information processing."
But for now, scientists don't know why crows seem to outpace primates in this particular type of decision-making. The study included only two birds and no direct comparisons to primates, so more work could be done to confirm the results and explore that question further.
For Nieder, observing the faster decision-making process in crows raises a broader question about how scientists define intelligence.
"Rather than assuming that the mammalian brain is the blueprint for intelligent behaviour," he said, "we can study different species to discover which computational principles are shared across animals and which reflect adaptations to their particular environments."
Are you a bird nerd? Find out with our bird quiz!
'> Crows may make lightning-fast decisions, sometimes twice as fast as humans, study hints