Clinical and Neuropathological Evaluations of the New Brunswick Neurological Syndrome of Unknown Cause.

Importance: In 2019, an alleged "mystery" neurological illness emerged in New Brunswick, Canada. Despite extensive media attention, no case description has been published to date. Objective: To report on 25 patients with a diagnosis of New Brunswick neurological syndrome of unknown cause (NSUC) who subsequently received a second, independent clinical reassessment or neuropathological examination between 2020 and 2025. Design, Setting, and Participants: This cross-sectional study of cases derived from a cohort of patients (n = 222) who had received an NSUC diagnosis. Four movement disorder neurologists and 2 behavioral neurologists carried out clinical evaluations at 2 hospitals in New Brunswick and Ontario, Canada. Neuropathological diagnoses were obtained in Ontario by a neuropathologist and a second reviewer, both blinded to the case histories. Eligible patients were offered a second opinion; 4 families of deceased patients provided consent for reporting autopsies and waivers of consent were obtained for 7. Exposure: NSUC as described in the case definition circulated by Public Health New Brunswick in 2021. Main Outcomes and Measures: Findings from the independent clinical evaluations and diagnoses obtained through neuropathological examination. Results: Among 105 eligible patients, 14 patients (aged 20-55 years; 8 female, 6 male) received clinical evaluations, and 11 patients (aged 56-82 years; 5 female, 6 male) had neuropathological diagnoses. Well-known conditions were identified in all 25 cases, including common neurodegenerative diseases, functional neurological disorder, traumatic brain injury, and metastatic cancer. Based on the 11 autopsy cases, a new disease was extremely unlikely, with a probability less than .001. When applying the 95% confidence interval for the true probability of no new disease, the data revealed a high probability between 87% and 100%. Conclusions and Relevance: There was no evidence supporting a diagnosis of NSUC in this cohort. The data inclusive of independent examinations and neuropathology strongly supported the presence of several neurodegenerative and non-neurodegenerative conditions. Unfounded concerns that a potentially fatal mystery disease, possibly induced by an environmental toxin, is causing the patients' neurological symptoms has been amplified in traditional and social media. Second, independent clinical evaluations are needed for any patient given a diagnosis of NSUC.