Independent evaluations refute claims of novel neurological disease in New Brunswick

In 2019, reports of a rapidly progressive dementia cluster in New Brunswick raised public and media concerns about a potential new neurological syndrome. Public Health New Brunswick (PHNB) launched an epidemiological investigation to determine possible environmental or toxic exposures.

In 2021, PHNB circulated the case definition term Neurological Syndrome of Unknown Cause (NSUC) as a provisional diagnostic label for patients presenting with neurological symptoms that did not conform to established disease criteria.

Use of the NSUC label was a way to consolidate disparate clinical presentations under a single term, facilitating data collection and coordinated investigation. Acknowledging diagnostic uncertainty, the term served as a placeholder pending clinical assessments and neuropathological studies to identify a possible underlying cause.

Media amplification of the term and fear of its implications contributed to widespread public speculation about an emerging neurological disorder.

Unsubstantiated claims of prion diseases, environmental toxins, and neurotoxic syndromes circulated, fueled by speculation and lack of concrete diagnostic clarity. No definitive cause or common exposure was identified, yet media reports escalated the case count to over 500, while PHNB identified only 222 potential cases.

Now, a University of Toronto-led investigation into the New Brunswick NSUC has identified well-established neurological conditions, including Alzheimer’s disease, Parkinson’s disease, and functional neurological disorder, with no evidence supporting the existence of a novel neurological disease.

In the study, “Clinical and Neuropathological Evaluations of the New Brunswick Neurological Syndrome of Unknown Cause,” published in JAMA Neurology, researchers from the University of Toronto and Horizon Health Network conducted a cross-sectional investigation to reassess the diagnoses of 25 patients previously classified under the NSUC designation. Objectives included determining whether the reported neurological cluster represented a novel disease or could be attributed to recognized neurological conditions.

Participants included 14 living patients who underwent independent clinical evaluations and 11 deceased patients whose neuropathological data were analyzed postmortem. Clinical assessments were conducted by four movement disorder neurologists and two behavioral neurologists, while neuropathological examinations were performed by a neuropathologist and a second reviewer. Both were blinded to clinical histories.

Electrophysiological testing, neurocognitive assessments, electroencephalograms, DaTscans, and ¹⁸F-fludeoxyglucose–positron emission tomography were all included in the evaluation methods. Neuropathological examinations involved extensive tissue sampling and immunohistochemical analysis for prion diseases, Alzheimer’s pathology, and other neurodegenerative markers.

Among the 14 living patients, discrepancies emerged between initial diagnoses and findings from second evaluations. Ten patients initially diagnosed with rapidly progressive dementia or other severe neurological disorders were, upon second independent evaluation, reclassified with a spectrum of well-characterized conditions,

These included Parkinson’s disease (n=3), progressive supranuclear palsy, behavioral-variant frontotemporal dementia, Alzheimer’s disease, functional neurological disorder, traumatic brain injury with postconcussion symptoms, alcohol-related cerebellar degeneration, narcolepsy, and, in one case, viral encephalitis as a secondary finding.

Autopsy findings for the 11 deceased patients revealed well-characterized neurological diseases, including Alzheimer’s disease, progressive supranuclear palsy, and metastatic adenocarcinoma.

Evidence of prion disease or other novel pathologies was absent in all cases. Statistical analysis indicated a probability of less than 0.001 for the existence of a new neurological disease within the original cohort of 222 cases. The 95% confidence interval suggested a likelihood between 87% and 100% that no new disease was present.

Researchers concluded that the clinical and neuropathological data did not support the existence of a novel neurological disease in the New Brunswick cohort.

Diagnostic inaccuracies were attributed to overinterpretation of ancillary testing, such as EEGs and SPECT-CT scans, and misclassification of functional neurological symptoms as neurodegenerative disorders. Recommendations emphasized the importance of second, independent clinical evaluations to prevent diagnostic misclassification and mitigate the impact of speculative diagnoses.

© 2025 Science X Network

In 2019, reports of a rapidly progressive dementia cluster in New Brunswick raised public and media concerns about a potential new neurological syndrome. Public Health New Brunswick (PHNB) launched an epidemiological investigation to determine possible environmental or toxic exposures.

In 2021, PHNB circulated the case definition term Neurological Syndrome of Unknown Cause (NSUC) as a provisional diagnostic label for patients presenting with neurological symptoms that did not conform to established disease criteria.

Use of the NSUC label was a way to consolidate disparate clinical presentations under a single term, facilitating data collection and coordinated investigation. Acknowledging diagnostic uncertainty, the term served as a placeholder pending clinical assessments and neuropathological studies to identify a possible underlying cause.

Media amplification of the term and fear of its implications contributed to widespread public speculation about an emerging neurological disorder.

Unsubstantiated claims of prion diseases, environmental toxins, and neurotoxic syndromes circulated, fueled by speculation and lack of concrete diagnostic clarity. No definitive cause or common exposure was identified, yet media reports escalated the case count to over 500, while PHNB identified only 222 potential cases.

Now, a University of Toronto-led investigation into the New Brunswick NSUC has identified well-established neurological conditions, including Alzheimer’s disease, Parkinson’s disease, and functional neurological disorder, with no evidence supporting the existence of a novel neurological disease.

In the study, “Clinical and Neuropathological Evaluations of the New Brunswick Neurological Syndrome of Unknown Cause,” published in JAMA Neurology, researchers from the University of Toronto and Horizon Health Network conducted a cross-sectional investigation to reassess the diagnoses of 25 patients previously classified under the NSUC designation. Objectives included determining whether the reported neurological cluster represented a novel disease or could be attributed to recognized neurological conditions.

Participants included 14 living patients who underwent independent clinical evaluations and 11 deceased patients whose neuropathological data were analyzed postmortem. Clinical assessments were conducted by four movement disorder neurologists and two behavioral neurologists, while neuropathological examinations were performed by a neuropathologist and a second reviewer. Both were blinded to clinical histories.

Electrophysiological testing, neurocognitive assessments, electroencephalograms, DaTscans, and ¹⁸F-fludeoxyglucose–positron emission tomography were all included in the evaluation methods. Neuropathological examinations involved extensive tissue sampling and immunohistochemical analysis for prion diseases, Alzheimer’s pathology, and other neurodegenerative markers.

Among the 14 living patients, discrepancies emerged between initial diagnoses and findings from second evaluations. Ten patients initially diagnosed with rapidly progressive dementia or other severe neurological disorders were, upon second independent evaluation, reclassified with a spectrum of well-characterized conditions,

These included Parkinson’s disease (n=3), progressive supranuclear palsy, behavioral-variant frontotemporal dementia, Alzheimer’s disease, functional neurological disorder, traumatic brain injury with postconcussion symptoms, alcohol-related cerebellar degeneration, narcolepsy, and, in one case, viral encephalitis as a secondary finding.

Autopsy findings for the 11 deceased patients revealed well-characterized neurological diseases, including Alzheimer’s disease, progressive supranuclear palsy, and metastatic adenocarcinoma.

Evidence of prion disease or other novel pathologies was absent in all cases. Statistical analysis indicated a probability of less than 0.001 for the existence of a new neurological disease within the original cohort of 222 cases. The 95% confidence interval suggested a likelihood between 87% and 100% that no new disease was present.

Researchers concluded that the clinical and neuropathological data did not support the existence of a novel neurological disease in the New Brunswick cohort.

Diagnostic inaccuracies were attributed to overinterpretation of ancillary testing, such as EEGs and SPECT-CT scans, and misclassification of functional neurological symptoms as neurodegenerative disorders. Recommendations emphasized the importance of second, independent clinical evaluations to prevent diagnostic misclassification and mitigate the impact of speculative diagnoses.

© 2025 Science X Network