Latest news with #AnthonyLang
Medscape
15-05-2025
- Health
- Medscape
Case Closed? Study Rules Out Mystery Neurologic Syndrome
What has been described as a mysterious neurologic syndrome of unknown cause (NSUC) in the Canadian province of New Brunswick is a 'perfect storm' of 'misdiagnosis, misdocumentation, and misinformation,' according to the senior author Anthony Lang, MD, professor and past director of neurology at the University of Toronto, Toronto, of a cross-sectional study of 25 of the cases. The study, which was published on May 7 in JAMA Neurology, found 'no support for the existence of an undiagnosed mystery disease' in a cross-section of 222 cases reported to Public Health New Brunswick (PHNB). Instead, the authors suggested that all patients had 'other diagnosable neurological conditions that could benefit from multidisciplinary treatment and other resources.' 'When you start to see the evidence, as we did, you realize that it's a house of cards,' Lang told Medscape Medical News. 'The consequences of this are immense,' he continued. 'Being told you have a mystery disease that could be fatal…a progressive, fatal disease with rapidly progressive dementia, is very harmful…and we really feel that patients who have received this diagnosis need to avail themselves of a proper second opinion by experts and then have the appropriate treatment when it's possible.' Low Uptake To be eligible for the study, New Brunswick patients had to have a provisional diagnosis of NSUC, atypical prion disease, neurotoxic syndrome, or rapidly progressive dementia (RPD). Eligible patients were invited to undergo additional testing and clinical evaluation by an independent expert. But because of the controversy around the issue, which has created political heat and public mistrust since the first cases were reported in 2019, many patients either refused (n = 52) or did not respond (n = 42) to the invitation. Among 105 patients originally assessed by Alier Marrero, MD, at the Moncton Interdisciplinary Neurodegenerative Diseases (MIND) clinic, Moncton, New Brunswick, which was set up to handle the problem, consent (or waiver of consent) was obtained for only 25 cases: 14 living and 11 deceased. The median age at symptom onset in the cohort was 55 years, ranging from 16 to 81 years. Data from patients' initial consultations and follow-ups were analyzed along with the results of a second, independent clinical evaluation by a movement disorders specialist or a behavioral neurologist. Additional testing included electrophysiology evaluation for movement disorders, complete neurocognitive assessment, EEG, Dopamine Transporter Scan, and [18F]fludeoxyglucose–positron emission tomography. For the deceased patients, autopsies included pathology evaluation as part of the Canadian Creutzfeldt-Jakob Disease Surveillance System with extensive tissue sampling and immunohistochemical analysis for prion diseases and other dementias. Other Diagnoses All 25 patients had 'definable and diagnosable neurological disorders that really refuted the concept of a mysterious brain disease of unknown cause or an NSIC,' said Lang. Diagnoses included Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy, other neurodegenerative conditions, functional neurologic disorder, traumatic brain injury, and persisting postconcussion symptoms, he said. 'Diagnostic inaccuracies stemmed from incorrect interpretation of histories (eg, overdiagnosis of RPD), inaccurate physical examination interpretation (eg, myoclonus, ataxia), and overreliance on or misinterpretation of ancillary testing such as EEG and SPECT [single-photon emission computed tomography],' wrote the study authors. 'The records were not accurate,' said Lang. 'They said the patient had hallucinations, or the patient had such and such. When we asked the patient who came back for a second opinion, they said, 'No, I never had that.' Or there was documentation of myoclonus, of ataxia, of dementia, and then we found no myoclonus, no ataxia, no dementia on clinical examination.' The researchers also used statistical modeling to calculate the probability of NSUC in the other cases not included in the study. 'We said, well, what about the other 200-some patients that had been documented in public health? What are the chances of any of them having a mysterious, undiagnosed neurological disease? And the statistics said that it was less than a one-in-a-million chance of any of those remaining patients having a mystery disease,' he said. 'So, we feel very confident that even though we have the small numbers, they are very, very convincing.' But Marrero disputed the JAMA findings. He first raised concerns with provincial health authorities in 2020 about a growing number of atypical RPD cases in the province, including several cases of Creutzfeldt-Jakob disease. Marrero was initially hired as one of the clinicians who followed the patients at MIND but was fired in 2022 for performance reasons and moved to the Dr Georges-L.-Dumont University Hospital Centre in Moncton. His patients were given the option to follow him or be assigned a new MIND clinician. An initial public health review and separate epidemiologic investigation of the first 48 cases concluded that the patients shared no common symptoms or syndrome. 'Although some of the cases have presentations with unusual symptomology, they do not appear to have a common illness with an unknown etiology, and there is no evidence of a cluster of a neurological syndrome of unknown cause,' it concluded, according to a provincial government website established to update the public. The investigation was closed, but after a provincial election in October 2024, the newly elected government reopened the investigation. Although public health authorities have officially recorded 222 cases, Marrero, who was disciplined for improper paperwork and reporting, told Medscape Medical News that he has now evaluated more than 500 patients in this cluster. 'I am appalled that a parallel investigation with a small number of patients has apparently been conducted for a long time without our knowledge or our patients' and families' knowledge,' he said. 'I am in profound disagreement with the study conclusions and have many questions regarding the methods and the content.' Not Convinced New Brunswick's Chief Medical Officer of Health, Yves Leger, MD, emphasized in a statement that the JAMA findings 'do not change my office's intention to complete its own investigation into cases of undiagnosed neurological illness in New Brunswick. Work has been underway on this matter since early 2023 with support from the Public Health Agency of Canada (PHAC).' 'There are too many unanswered questions for us to stop the work that Public Health is doing to be able to provide patients — and potentially future patients — with the information they need about what's causing these illnesses,' New Brunswick Premier Susan Holt told reporters in reaction to the JAMA findings. 'On request from PHNB, PHAC has also agreed to conduct a scientific review of the investigation findings once PHNB has completed its analysis and interpretation,' said a spokesperson for PHAC. 'I trust that the current process of independent multidisciplinary scientific investigation and extensive file analysis that is underway by our public health authorities could provide appropriate answers to our communities,' said Marrero. 'We are hopeful that this process would include not only comprehensive additional patient testing but also testing for water, food, soil, and air samples in the affected areas, as well as additional patient support and effective prevention and treatment measures.' But Connie Marras, MD, PhD, a University of Toronto neurologist and movement disorder specialist with an expertise in epidemiology, questioned the need for further investigation. 'It is premature to start looking at any environmental agents that might be responsible for this before we have evidence that there is indeed a cluster, and both the investigations that have been done so far don't support that,' Marras, who was not involved in any of the investigations, told Medscape Medical News. 'The evidence that has been pulled together to date strongly suggests that there is not a unifying, underlying diagnosis for these individuals.' If the current evidence is insufficient to convince public health and the public, then an ideal next step, from an epidemiologic point of view, would be to test a larger, random sample of patients, she said. The limitations of the JAMA study included small numbers and the potential for selection bias. 'If the purportedly affected people are willing to submit to further evaluation, their engagement in this is critical, for the sake of everybody.' The study 'underscores the critical importance of systematic data collection and objective evaluation (seeing) in cases of neurological syndromes with unknown causes,' wrote Michael Okun, MD, professor of neurology and director of the Norman Fixel Institute for Neurological Diseases at the University of Florida Health in Gainesville, Florida, in a post on X. 'I completely agree with the authors that these types of unknown 'neuro' cases are 'complex neurological disorders [that will] benefit from a second, independent and/or subspecialist evaluation and require multidisciplinary support throughout the diagnostic journey.' Always ask yourself, 'Do you see what you want to see? Are you being rigorous and as unbiased as possible? Are you open to revising your initial impressions? Can a second look enhance diagnostic accuracy and outcomes?'…These authors are sharing hard data to help us to understand a phenomenon. We must always seek clarity.' No funding source for the study was reported. Lang reported receiving personal fees from AbbVie, AFFiRis, Alector, Amylyx Pharmaceuticals, APRINOIA Therapeutics, Biogen, BioAdvance, Biohaven, BioVie, BlueRock, Bristol Myers Squibb, Cavion, CoA Therapeutics, Denali, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Lilly, Novartis, Paladin, Pharma Two B Ltd., PsychoGenics, Roche, Sun Pharma, and UCB outside the submitted work and litigation related to paraquat and Parkinson's disease (for the plaintiffs). Marrero and Marras reported having no relevant financial relationships.
Yahoo
08-05-2025
- Health
- Yahoo
UHN study finds patients diagnosed with New Brunswick "mystery brain disease" have diagnosable neurological conditions
TORONTO, May 7, 2025 /CNW/ - A study published today in JAMA Neurology has found patients previously diagnosed with a "mystery brain disease" that emerged in New Brunswick, Canada, had known neurological conditions—some involving brain cell damage, such as dementia, and others not involving degeneration, like head injuries. 'Involving input from various health care professionals such as neurologists, psychologists, and rehabilitation specialists can play a vital role in guiding patients through complex and uncertain diagnostic journeys,' says Dr. Anthony Lang, neurologist, Senior Scientist at UHN's Krembil Brain Institute and senior author of the study. (Credit: University Health Network) (CNW Group/University Health Network) Led by Dr. Anthony Lang, a neurologist and Senior Scientist at University Health Network's (UHN) Krembil Brain Institute, the study was a collaboration between Horizon Health Network in New Brunswick and UHN in Toronto. It involved a detailed clinical and pathological (post-mortem tissue) analysis of 25 individuals previously labeled as having New Brunswick Neurological Syndrome of Unknown Cause (NSUC). Researchers conducted independent clinical evaluations of 14 patients and autopsy evaluations of 11 deceased individuals. Most of the 105 patients originally identified either did not respond or declined the offer for further investigation. "We found that what had been termed a 'mystery brain disease' was, in fact, a collection of identifiable medical conditions," said Dr. Lang. "These included well-characterized neurological disorders, such as Parkinson's disease, dementia, traumatic brain injury, and functional neurological disorder, a condition where physical symptoms like tremors or memory issues occur without clear structural brain damage." The research team reviewed clinical records and diagnostic tests—including MRI scans, brain blood flow studies, and electroencephalograms (EEGs), which measure electrical activity in the brain—spanning from 2019 to 2025. They found no evidence of a novel or previously unidentified disease in any of the 25 cases. The study also revealed significant discrepancies in many cases between the original clinical documentation and the findings from the second, independent assessments. Some diagnoses leaned too heavily on specific tests without enough clinical context on certain diagnostic tests. In all 25 cases, researchers found no evidence of a new disease. "By analyzing the data, we were able to clarify the specific conditions contributing to the patients' symptoms," said Dr. Nathaniel Bendahan, a UHN Clinical Research Fellow at the time and first author of this study. "Rather than a single new disease, we found a range of distinct neurological diseases." The findings underscore the importance of expert second opinions in complex or uncertain neurological cases—especially when initial diagnoses are unclear.
Yahoo
07-05-2025
- Health
- Yahoo
Mysterious brain diseases in Canada weren't a mystery after all
Six years ago, a Canadian neurologist claimed to notice strange symptoms in a cluster of patients in New Brunswick, a province bordering Maine. According to the neurologist, Dr. Alier Marrero, the patients suffered hallucinations, spasms, rapid memory loss and the sensation that bugs were crawling underneath their skin, but their symptoms and brain scans didn't neatly fit an existing diagnosis. In other words, the cases were a mystery. But since then, neurologists who have reviewed the cases have identified clear diagnoses, including Alzheimer's, Parkinson's and cancer. A study published this week in JAMA Neurology reinforces those findings, putting the probability of a mystery disease at roughly 1 in a million. Doctors working on the study evaluated 25 people who had been identified as part of the New Brunswick cluster. Eleven of the patients had died, so neuropathologists used autopsies to determine their illnesses. For the 14 living patients, neurologists relied on cognitive assessments, among other tests. They concluded that all of the patients had well-known conditions such as Alzheimer's, Parkinson's, cancer, traumatic brain injuries or post-concussion symptoms. 'We really felt we had a good explanation for 100% of the cases,' said an author of the study, Dr. Anthony Lang, a neurologist at University Health Network's Krembil Brain Institute. However, some doctors worry it won't be enough to quash speculation that the cases have an unknown origin — a theory many patients and their families have clung to. According to the study authors, 52 people identified as part of the New Brunswick cluster refused second opinions, and 42 more didn't respond to the authors' reaching out. The study attributes that to declining trust in health institutions and the spread of misinformation on both traditional and social media. 'These were examples of misdiagnosis that then led to misinformation. And sadly, the physician involved continues to believe and convince the patients and families that they have a mysterious illness,' Lang said. Marrero took issue with the study and its findings in a statement. 'I am in profound disagreement with the study conclusions and have many questions regarding the methods and the content,' he said. 'I am sure that our patients, families, and communities share the same very serious concerns.' Dr. Valerie Sim, an associate professor of neurology at the University of Alberta who wasn't involved in the study, said there has been no proof that the patients' illnesses are related. In fact, she said, the cases are 'so broad in their description that we could all have this mysterious illness.' 'Sadly, the one thing that all the patients have in common is the same neurologist,' Sim said. 'And the patients who have been seen by other neurologists get a diagnosis of a known entity that's not a mystery.' James Mastrianni, a neurology professor at the University of Chicago who wasn't part of the research, said the study reinforces that 'a second opinion by an expert in the field is often helpful.' An ongoing investigation The mystery illness theory gained traction in 2021 when Canadian health authorities began investigating cases based on Marrero's reports. But even after the investigation determined that most patients had known conditions, some families were skeptical. In November, the premier of New Brunswick, Susan Holt, called on the province's health minister to conduct a scientific review 'into the mystery brain disease.' 'New Brunswickers deserve answers,' Holt said in a statement last year. 'We need to know what's making us sick.' Some patient advocates now believe an environmental exposure is triggering the illnesses, claiming patients' blood and urine tests show the presence of heavy metals, pesticides and rare antibodies that warrant further study. 'It wasn't ever about whether a patient could have an alternative diagnosis,' said Kat Lanteigne, an advocate from New Brunswick. 'It was what has triggered them to have this neurodegenerative disease?' Dr. Yves Léger, New Brunswick's chief medical officer of health, said in a statement Wednesday that the new study 'doesn't change my Office's intention to complete its own investigation into cases of undiagnosed neurological illness in New Brunswick.' His office has received 222 reports of cases identified as part of the cluster. Marrero said he has 'evaluated more than 500 patients in this cluster, and provided a significant amount of unequivocal, sometimes critical environmental exposure evidences, as well as rare autoimmune markers in many of them.' But Lang said that just because a substance is in blood or urine doesn't mean it caused someone's neurological symptoms. 'You don't do a shotgun approach looking for anything and everything and then finding something and claiming it's related to what the problem is,' he said. The challenge of diagnosing neurological issues Neurologists with no connection to the New Brunswick cases point to a few reasons advocates, doctors and government officials are still debating the cause of the illnesses. For one, they said, accurate diagnoses can take time. And some of the conditions detected in the study, like Alzheimer's, can have complex presentations. 'It really takes a cohesive story from the family and a timeline to understand if someone is developing dementia. There can be confusing signs on a neurologic exam,' said Dr. Kimberly O'Neill, a neurologist in the NYU Langone Health Multiple Sclerosis Comprehensive Care Center. One of the core symptoms used to identify the New Brunswick patients was rapidly progressing dementia. But families sometimes miss early signs of neurodegeneration, making it appear that dementia came on suddenly, Mastrianni said. Once debilitating symptoms arrive, patients and their families are often desperate for answers and may be reluctant to let go of the first diagnoses they get, Sim said. 'We see this all the time in medicine, that patients gravitate to a diagnosis or a group entity,' Sim said. 'That's clearly what's happening here.' The misdiagnoses are 'really a tragedy,' she added, because patients could be missing out on treatments or proper care. This article was originally published on
NBC News
07-05-2025
- Health
- NBC News
Mysterious brain diseases in Canada weren't a mystery after all
Six years ago, a Canadian neurologist claimed to notice strange symptoms in a cluster of patients in New Brunswick, a province bordering Maine. According to the neurologist, Dr. Alier Marrero, the patients suffered hallucinations, spasms, rapid memory loss and the sensation that bugs were crawling underneath their skin, but their symptoms and brain scans didn't neatly fit an existing diagnosis. In other words, the cases were a mystery. But since then, neurologists who have reviewed the cases have identified clear diagnoses, including Alzheimer's, Parkinson's and cancer. A study published this week in JAMA Neurology reinforces those findings, putting the probability of a mystery disease at roughly 1 in a million. Doctors working on the study evaluated 25 people who had been identified as part of the New Brunswick cluster. Eleven of the patients had died, so neuropathologists used autopsies to determine their illnesses. For the 14 living patients, neurologists relied on cognitive assessments, among other tests. They concluded that all of the patients had well-known conditions such as Alzheimer's, Parkinson's, cancer, traumatic brain injuries or post-concussion symptoms. 'We really felt we had a good explanation for 100% of the cases,' said an author of the study, Dr. Anthony Lang, a neurologist at University Health Network's Krembil Brain Institute. However, some doctors worry it won't be enough to quash speculation that the cases have an unknown origin — a theory many patients and their families have clung to. According to the study authors, 52 people identified as part of the New Brunswick cluster refused second opinions, and 42 more didn't respond to the authors' reaching out. The study attributes that to declining trust in health institutions and the spread of misinformation on both traditional and social media. 'These were examples of misdiagnosis that then led to misinformation. And sadly, the physician involved continues to believe and convince the patients and families that they have a mysterious illness,' Lang said. Marrero took issue with the study and its findings in a statement. 'I am in profound disagreement with the study conclusions and have many questions regarding the methods and the content,' he said. 'I am sure that our patients, families, and communities share the same very serious concerns.' Dr. Valerie Sim, an associate professor of neurology at the University of Alberta who wasn't involved in the study, said there has been no proof that the patients' illnesses are related. In fact, she said, the cases are 'so broad in their description that we could all have this mysterious illness.' 'Sadly, the one thing that all the patients have in common is the same neurologist,' Sim said. 'And the patients who have been seen by other neurologists get a diagnosis of a known entity that's not a mystery.' James Mastrianni, a neurology professor at the University of Chicago who wasn't part of the research, said the study reinforces that 'a second opinion by an expert in the field is often helpful.' An ongoing investigation The mystery illness theory gained traction in 2021 when Canadian health authorities began investigating cases based on Marrero's reports. But even after the investigation determined that most patients had known conditions, some families were skeptical. In November, the premier of New Brunswick, Susan Holt, called on the province's health minister to conduct a scientific review 'into the mystery brain disease.' 'New Brunswickers deserve answers,' Holt said in a statement last year. 'We need to know what's making us sick.' Some patient advocates now believe an environmental exposure is triggering the illnesses, claiming patients' blood and urine tests show the presence of heavy metals, pesticides and rare antibodies that warrant further study. 'It wasn't ever about whether a patient could have an alternative diagnosis,' said Kat Lanteigne, an advocate from New Brunswick. 'It was what has triggered them to have this neurodegenerative disease?' Dr. Yves Léger, New Brunswick's chief medical officer of health, said in a statement Wednesday that the new study 'doesn't change my Office's intention to complete its own investigation into cases of undiagnosed neurological illness in New Brunswick.' His office has received 222 reports of cases identified as part of the cluster. Marrero said he has 'evaluated more than 500 patients in this cluster, and provided a significant amount of unequivocal, sometimes critical environmental exposure evidences, as well as rare autoimmune markers in many of them.' But Lang said that just because a substance is in blood or urine doesn't mean it caused someone's neurological symptoms. 'You don't do a shotgun approach looking for anything and everything and then finding something and claiming it's related to what the problem is,' he said. The challenge of diagnosing neurological issues Neurologists with no connection to the New Brunswick cases point to a few reasons advocates, doctors and government officials are still debating the cause of the illnesses. For one, they said, accurate diagnoses can take time. And some of the conditions detected in the study, like Alzheimer's, can have complex presentations. 'It really takes a cohesive story from the family and a timeline to understand if someone is developing dementia. There can be confusing signs on a neurologic exam,' said Dr. Kimberly O'Neill, a neurologist in the NYU Langone Health Multiple Sclerosis Comprehensive Care Center. One of the core symptoms used to identify the New Brunswick patients was rapidly progressing dementia. But families sometimes miss early signs of neurodegeneration, making it appear that dementia came on suddenly, Mastrianni said. Once debilitating symptoms arrive, patients and their families are often desperate for answers and may be reluctant to let go of the first diagnoses they get, Sim said. 'We see this all the time in medicine, that patients gravitate to a diagnosis or a group entity,' Sim said. 'That's clearly what's happening here.'
Malaysian Reserve
07-05-2025
- Health
- Malaysian Reserve
UHN study finds patients diagnosed with New Brunswick "mystery brain disease" have diagnosable neurological conditions
TORONTO, May 7, 2025 /CNW/ – A study published today in JAMA Neurology has found patients previously diagnosed with a 'mystery brain disease' that emerged in New Brunswick, Canada, had known neurological conditions—some involving brain cell damage, such as dementia, and others not involving degeneration, like head injuries. UHN study finds patients diagnosed with New Brunswick 'mystery brain disease' have diagnosable neurological conditions Led by Dr. Anthony Lang, a neurologist and Senior Scientist at University Health Network's (UHN) Krembil Brain Institute, the study was a collaboration between Horizon Health Network in New Brunswick and UHN in Toronto. It involved a detailed clinical and pathological (post-mortem tissue) analysis of 25 individuals previously labeled as having New Brunswick Neurological Syndrome of Unknown Cause (NSUC). Researchers conducted independent clinical evaluations of 14 patients and autopsy evaluations of 11 deceased individuals. Most of the 105 patients originally identified either did not respond or declined the offer for further investigation. 'We found that what had been termed a 'mystery brain disease' was, in fact, a collection of identifiable medical conditions,' said Dr. Lang. 'These included well-characterized neurological disorders, such as Parkinson's disease, dementia, traumatic brain injury, and functional neurological disorder, a condition where physical symptoms like tremors or memory issues occur without clear structural brain damage.' The research team reviewed clinical records and diagnostic tests—including MRI scans, brain blood flow studies, and electroencephalograms (EEGs), which measure electrical activity in the brain—spanning from 2019 to 2025. They found no evidence of a novel or previously unidentified disease in any of the 25 cases. The study also revealed significant discrepancies in many cases between the original clinical documentation and the findings from the second, independent assessments. Some diagnoses leaned too heavily on specific tests without enough clinical context on certain diagnostic tests. In all 25 cases, researchers found no evidence of a new disease. 'By analyzing the data, we were able to clarify the specific conditions contributing to the patients' symptoms,' said Dr. Nathaniel Bendahan, a UHN Clinical Research Fellow at the time and first author of this study. 'Rather than a single new disease, we found a range of distinct neurological diseases.' The findings underscore the importance of expert second opinions in complex or uncertain neurological cases—especially when initial diagnoses are unclear. 'Involving input from various health care professionals such as neurologists, psychologists, and rehabilitation specialists can play a vital role in guiding patients through complex and uncertain diagnostic journeys,' added Dr. Lang. About the Krembil Brain Institute The Krembil Brain Institute at Toronto Western Hospital, part of University Health Network, is home to one of the world's largest and most comprehensive teams of physicians and scientists uniquely working hand-in-hand to prevent and confront problems of the brain and spine. One in three Canadians will experience a brain-related condition such as Parkinson's, Alzheimer's or epilepsy in their lifetime. Through state-of-the-art patient care and advanced research, we are working relentlessly to find new treatments and cures. For more information, visit: About University Health Network UHN is Canada's No. 1 hospital and the world's No. 1 publicly funded hospital. With 10 sites and more than 44,000 TeamUHN members, UHN consists of Toronto General Hospital, Toronto Western Hospital, Princess Margaret Cancer Centre, Toronto Rehabilitation Institute, The Michener Institute of Education and West Park Healthcare Centre. As Canada's top research hospital, the scope of biomedical research and complexity of cases at UHN have made it a national and international source for discovery, education, and patient care. UHN has the largest hospital-based research program in Canada, with major research in neurosciences, cardiology, transplantation, oncology, surgical innovation, infectious diseases, genomic medicine and rehabilitation medicine. UHN is a research hospital affiliated with the University of Toronto. For more information, visit: SOURCE University Health Network
