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SAN DIEGO –
The problem is that MS can vary greatly in its presentation, and many symptoms can mimic other conditions, according to Eoin Flanagan, MBBCh, who discussed the issue during a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Mimics and red flags
Dr. Flanagan noted a study that found common themes among MS misdiagnoses. “Many of these conditions are common conditions that we see in our neurology clinic – for example, migraine, fibromyalgia, nonspecific symptoms with an abnormal MRI, or functional neurologic disorder. If you’re teaching medical students or trainees about MS misdiagnosis, it’s important to give this example to show that these are not the zebras that are misdiagnosed, but actually common conditions that we see in our clinics,” said Dr. Flanagan, a neurologist at Mayo Clinic in Rochester, Minn.
Evaluation of MS mimics isn’t always necessary. Much of the time, typical clinical, neurologic, and imaging features provide a clear diagnosis. But some features can be red flags that MS may not be the cause. These can include a cerebrospinal fluid white blood cell count higher than 50, elevated CSF protein with normal white cell counts, low glucose, and negative oligoclonal bands, all of which could signify a range of other conditions.
These and other red flags should prompt a careful look to get the right diagnosis.
Earlier diagnosis = better outcomes
“[Evidence has] shown recently that as the diagnostic criteria have become more sensitive and we diagnose MS earlier, patients have had better outcomes because they’ve been able to initiate treatment earlier,” said Andrew Solomon, MD, who is an associate professor of neurologic sciences and division chief of multiple sclerosis at University of Vermont, Burlington. Dr. Solomon, Dr. Flanagan, and others are currently writing a review article on differential diagnosis of MS that will update the last review, published in 2008.
“Differential diagnosis has become more complex as we’ve had a broader understanding of disorders that can mimic MS. In the meantime, we still don’t have a highly sensitive and specific biomarker for MS that can help guide us when we first see somebody,” said Dr. Solomon.
Look for patterns and imaging clues
Dr. Flanagan’s talk had several points of emphasis. A key feature is the length of time between when the patient develops the first symptom and maximal symptoms. “If that’s very quick, then that suggests it’s a spinal cord stroke. If it comes down over days to a few weeks, then that suggests inflammation like MS, or like neuromyelitis optica [NMO] or myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]. As it progresses beyond 21 days, then we’re going to be thinking about a different diagnosis,” said Dr. Flanagan.
Dr. Flanagan also noted the usefulness of specific features of the spinal cord MRI. Variables like lesion length, location in the center or periphery of the spinal cord, and characteristics of the enhancement pattern may be useful. “The pattern of gadolinium enhancement can be useful in narrowing your differential diagnosis and suggesting the correct diagnosis. For example, the flat pancake-like enhancement on sagittal images can suggest cervical spondylosis, while trident sign on axial images can suggest spinal cord sarcoidosis. Prior studies have shown that education on these patterns can enhance diagnosis.”
Dr. Flanagan suggested that both radiologists and neurologists should be trained to recognize such patterns. “If you educate radiologists or neurologists on these patterns, it can help them with diagnosis.”
Common mistakes
MOGAD and aquaporin 4–positive NMO spectrum disorder (AQP4+NMOSD) can be easily mistaken for MS, but there are some key differences. MOGAD and AQP4+NMOSD attacks are more severe than MS attacks, leaving patients more likely to be blind following an optic neuritis attack or wheelchair bound because of myelitis. More than 85% of CSF from patients with MS have oligoclonal bands versus about 15% of CSF from patients with MOGAD or AQP4+NMOSD. There is also a difference in lesion dynamics over time: MOGAD T2 lesions frequently resolve over follow-up while AQP4+NMOSD and MS lesions typically continue and leave a scar and persist. Silent lesions are more likely during surveillance MRI among MS patients, but are rare in MOGAD and AQP4+NMOSD, according to Dr. Flanagan. “One caveat to this is that with stronger MS medications we are seeing less silent lesions accumulating as we use those treatments more often.”
Dr. Solomon has been done nonpromotional speaking for EMD Serono. He has received research funding from Bristol-Myers Squibb. He has been on an advisory board or consulted for Greenwich Biosciences, TG Therapeutics, Octave Bioscience, and Horizon Therapeutics. Dr. Flanagan has no relevant financial disclosures. Dr. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB.
SAN DIEGO –
The problem is that MS can vary greatly in its presentation, and many symptoms can mimic other conditions, according to Eoin Flanagan, MBBCh, who discussed the issue during a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Mimics and red flags
Dr. Flanagan noted a study that found common themes among MS misdiagnoses. “Many of these conditions are common conditions that we see in our neurology clinic – for example, migraine, fibromyalgia, nonspecific symptoms with an abnormal MRI, or functional neurologic disorder. If you’re teaching medical students or trainees about MS misdiagnosis, it’s important to give this example to show that these are not the zebras that are misdiagnosed, but actually common conditions that we see in our clinics,” said Dr. Flanagan, a neurologist at Mayo Clinic in Rochester, Minn.
Evaluation of MS mimics isn’t always necessary. Much of the time, typical clinical, neurologic, and imaging features provide a clear diagnosis. But some features can be red flags that MS may not be the cause. These can include a cerebrospinal fluid white blood cell count higher than 50, elevated CSF protein with normal white cell counts, low glucose, and negative oligoclonal bands, all of which could signify a range of other conditions.
These and other red flags should prompt a careful look to get the right diagnosis.
Earlier diagnosis = better outcomes
“[Evidence has] shown recently that as the diagnostic criteria have become more sensitive and we diagnose MS earlier, patients have had better outcomes because they’ve been able to initiate treatment earlier,” said Andrew Solomon, MD, who is an associate professor of neurologic sciences and division chief of multiple sclerosis at University of Vermont, Burlington. Dr. Solomon, Dr. Flanagan, and others are currently writing a review article on differential diagnosis of MS that will update the last review, published in 2008.
“Differential diagnosis has become more complex as we’ve had a broader understanding of disorders that can mimic MS. In the meantime, we still don’t have a highly sensitive and specific biomarker for MS that can help guide us when we first see somebody,” said Dr. Solomon.
Look for patterns and imaging clues
Dr. Flanagan’s talk had several points of emphasis. A key feature is the length of time between when the patient develops the first symptom and maximal symptoms. “If that’s very quick, then that suggests it’s a spinal cord stroke. If it comes down over days to a few weeks, then that suggests inflammation like MS, or like neuromyelitis optica [NMO] or myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]. As it progresses beyond 21 days, then we’re going to be thinking about a different diagnosis,” said Dr. Flanagan.
Dr. Flanagan also noted the usefulness of specific features of the spinal cord MRI. Variables like lesion length, location in the center or periphery of the spinal cord, and characteristics of the enhancement pattern may be useful. “The pattern of gadolinium enhancement can be useful in narrowing your differential diagnosis and suggesting the correct diagnosis. For example, the flat pancake-like enhancement on sagittal images can suggest cervical spondylosis, while trident sign on axial images can suggest spinal cord sarcoidosis. Prior studies have shown that education on these patterns can enhance diagnosis.”
Dr. Flanagan suggested that both radiologists and neurologists should be trained to recognize such patterns. “If you educate radiologists or neurologists on these patterns, it can help them with diagnosis.”
Common mistakes
MOGAD and aquaporin 4–positive NMO spectrum disorder (AQP4+NMOSD) can be easily mistaken for MS, but there are some key differences. MOGAD and AQP4+NMOSD attacks are more severe than MS attacks, leaving patients more likely to be blind following an optic neuritis attack or wheelchair bound because of myelitis. More than 85% of CSF from patients with MS have oligoclonal bands versus about 15% of CSF from patients with MOGAD or AQP4+NMOSD. There is also a difference in lesion dynamics over time: MOGAD T2 lesions frequently resolve over follow-up while AQP4+NMOSD and MS lesions typically continue and leave a scar and persist. Silent lesions are more likely during surveillance MRI among MS patients, but are rare in MOGAD and AQP4+NMOSD, according to Dr. Flanagan. “One caveat to this is that with stronger MS medications we are seeing less silent lesions accumulating as we use those treatments more often.”
Dr. Solomon has been done nonpromotional speaking for EMD Serono. He has received research funding from Bristol-Myers Squibb. He has been on an advisory board or consulted for Greenwich Biosciences, TG Therapeutics, Octave Bioscience, and Horizon Therapeutics. Dr. Flanagan has no relevant financial disclosures. Dr. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB.
SAN DIEGO –
The problem is that MS can vary greatly in its presentation, and many symptoms can mimic other conditions, according to Eoin Flanagan, MBBCh, who discussed the issue during a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Mimics and red flags
Dr. Flanagan noted a study that found common themes among MS misdiagnoses. “Many of these conditions are common conditions that we see in our neurology clinic – for example, migraine, fibromyalgia, nonspecific symptoms with an abnormal MRI, or functional neurologic disorder. If you’re teaching medical students or trainees about MS misdiagnosis, it’s important to give this example to show that these are not the zebras that are misdiagnosed, but actually common conditions that we see in our clinics,” said Dr. Flanagan, a neurologist at Mayo Clinic in Rochester, Minn.
Evaluation of MS mimics isn’t always necessary. Much of the time, typical clinical, neurologic, and imaging features provide a clear diagnosis. But some features can be red flags that MS may not be the cause. These can include a cerebrospinal fluid white blood cell count higher than 50, elevated CSF protein with normal white cell counts, low glucose, and negative oligoclonal bands, all of which could signify a range of other conditions.
These and other red flags should prompt a careful look to get the right diagnosis.
Earlier diagnosis = better outcomes
“[Evidence has] shown recently that as the diagnostic criteria have become more sensitive and we diagnose MS earlier, patients have had better outcomes because they’ve been able to initiate treatment earlier,” said Andrew Solomon, MD, who is an associate professor of neurologic sciences and division chief of multiple sclerosis at University of Vermont, Burlington. Dr. Solomon, Dr. Flanagan, and others are currently writing a review article on differential diagnosis of MS that will update the last review, published in 2008.
“Differential diagnosis has become more complex as we’ve had a broader understanding of disorders that can mimic MS. In the meantime, we still don’t have a highly sensitive and specific biomarker for MS that can help guide us when we first see somebody,” said Dr. Solomon.
Look for patterns and imaging clues
Dr. Flanagan’s talk had several points of emphasis. A key feature is the length of time between when the patient develops the first symptom and maximal symptoms. “If that’s very quick, then that suggests it’s a spinal cord stroke. If it comes down over days to a few weeks, then that suggests inflammation like MS, or like neuromyelitis optica [NMO] or myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]. As it progresses beyond 21 days, then we’re going to be thinking about a different diagnosis,” said Dr. Flanagan.
Dr. Flanagan also noted the usefulness of specific features of the spinal cord MRI. Variables like lesion length, location in the center or periphery of the spinal cord, and characteristics of the enhancement pattern may be useful. “The pattern of gadolinium enhancement can be useful in narrowing your differential diagnosis and suggesting the correct diagnosis. For example, the flat pancake-like enhancement on sagittal images can suggest cervical spondylosis, while trident sign on axial images can suggest spinal cord sarcoidosis. Prior studies have shown that education on these patterns can enhance diagnosis.”
Dr. Flanagan suggested that both radiologists and neurologists should be trained to recognize such patterns. “If you educate radiologists or neurologists on these patterns, it can help them with diagnosis.”
Common mistakes
MOGAD and aquaporin 4–positive NMO spectrum disorder (AQP4+NMOSD) can be easily mistaken for MS, but there are some key differences. MOGAD and AQP4+NMOSD attacks are more severe than MS attacks, leaving patients more likely to be blind following an optic neuritis attack or wheelchair bound because of myelitis. More than 85% of CSF from patients with MS have oligoclonal bands versus about 15% of CSF from patients with MOGAD or AQP4+NMOSD. There is also a difference in lesion dynamics over time: MOGAD T2 lesions frequently resolve over follow-up while AQP4+NMOSD and MS lesions typically continue and leave a scar and persist. Silent lesions are more likely during surveillance MRI among MS patients, but are rare in MOGAD and AQP4+NMOSD, according to Dr. Flanagan. “One caveat to this is that with stronger MS medications we are seeing less silent lesions accumulating as we use those treatments more often.”
Dr. Solomon has been done nonpromotional speaking for EMD Serono. He has received research funding from Bristol-Myers Squibb. He has been on an advisory board or consulted for Greenwich Biosciences, TG Therapeutics, Octave Bioscience, and Horizon Therapeutics. Dr. Flanagan has no relevant financial disclosures. Dr. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB.
FROM ACTRIMS FORUM 2023