A neurological syndrome of unknown cause was suggested as a potential novel degenerative disease in a cluster of individuals with similar clinical signs and symptoms in the Canadian province of New Brunswick beginning in 2019. The existence of this syndrome became the subject of several investigations including by federal and provincial governments, extensive media coverage, and scientific scrutiny. Symptoms listed on the New Brunswick Public Health (NBPH) website include memory problems, muscle spasms, balance problems, difficulty walking or falls, blurred vision or visual hallucinations, unexplained or significant weight loss, behaviour changes, and pain in the upper or lower limbs.
The existence of the neurological syndrome was originally promoted by neurologist Alier Marrero, who diagnosed hundreds of patients with the condition. Subsequent investigations by other neurologists, neuropathologists, and the Province of New Brunswick suggest that the syndrome does not correspond to a single neurological disease, that all re-examined cases of the proposed neurological syndrome corresponded to well-known conditions such as Parkinson's disease and Alzheimer's disease, that some alleged symptoms could not be substantiated upon re-examination, that the rapidity of onset had been overestimated in some cases, and that a single underlying cause for the proposed syndrome cannot be identified.
Background The investigation into the cluster was instigated in 2019 at the federal level by the Ottawa-based Creutzfeldt-Jakob Disease Surveillance System (CJDSS) unit – which operates under Public Health Agency of Canada (PHAC). CJDSS director Michael Coulthart worked with Alier Marrero, a neurologist at Dr. Georges-L.-Dumont University Hospital Centre, in Moncton, New Brunswick who had referred cases to the CJDSS unit for testing and diagnosis. The disease cluster was first noted through the routine case management arrangement between New Brunswick and federal health authorities, when experts from the CJDSS unit – which provides surveillance for "all types of human prion disease in Canada" – noticed a significant number of NB referrals had "some common symptoms and similar potential diagnostic profiles". The CJDSS ruled out any prion disorder, including Creutzfeldt-Jakob Disease (CJD) – an incurable, fatal disease. Marrero and Coulthart and colleagues worked for months together investigating the cases. The federal-provincial team began to suspect that they were looking at a novel neurological degenerative disease potentially caused by a toxin or agent. By December 2020, 24 new cases in New Brunswick of something that "looked like CJD but was not" had been diagnosed. PHAC considered this to be an "unusually high number" and contacted New Brunswick's Chief Medical Officer of Health (CMOH) Jennifer Russell, about the disease cluster. In January 2021, the CJDSS and Marrero updated the case definition of the syndrome, which had been first drafted in December 2020. The definition was then accepted by Public Health New Brunswick.
In March 2021, provincial health authorities shared information describing symptoms with New Brunswick physicians in a memorandum that was leaked to the media. On 27 April 2021, NBPH published a webpage which is updated to inform the public of the disease cluster, its symptoms, ongoing investigations and their findings.
Symptoms In a 25 March 2021 interview, Marrero said that initial symptoms are often nonspecific, making a diagnosis challenging. He listed symptoms such as "behavioral changes, sleep disturbances, unexplained pain, visual hallucinations, coordination problems, unexplained hair loss, involuntary muscle twitching, formication (a sensation that feels like small insects crawling under the skin), ataxia, and brain atrophy".
In April the NBPH website listed symptoms such as memory problems, muscle spasms, balance issues, difficulty walking or falls, blurred vision or visual hallucinations, unexplained or significant weight loss, behaviour changes and pain in the upper or lower limbs.
In interviews conducted by the media, patients and their families described symptoms such as rapidly progressing dementia, unexplained and significant weight loss, myoclonus, aphasia, changes in behaviour, sleep disturbances, unexplained pain, visual hallucinations, co-ordination problems and severe muscle and brain atrophy, progressing over a period of 18 to 36 months. The majority experience multi-day insomnia even with "sleep medication". Memory loss and aphasia are seen. In some cases, Capgras delusion and echolalia have been reported. Myoclonus persists "even in the late stages of the disease" and even "when patients are unconscious". Akinetic mutism were observed in late-stage patients, where they no longer have the ability to speak or move. The New York Times reported symptoms of "extreme fatigue, involuntary jerking movements, memory lapses and hallucinations" on 4 June 2021.
Demographics The cases suggest that the proposed syndrome affects men and women equally. Cases have been reported in all age groups from 18 to 86, with a median age of patients being 59 years old.
Etiology The working name used by investigators to the disease was "neurological syndrome of unknown etiology in New Brunswick". The CMOH referred to it as progressive neurological syndrome of unknown cause", and it is now called "neurological syndrome of unknown cause" on the NBPH website.
A 17 March 2021 CBC News report said that the disease was not genetic, and could be contracted from water, food or air.
According to a 25 March 2021 Medscape Medical News article, Marrero said that some experts considered the possibility that Creutzfeldt-Jakob Lookalike might be a "toxic, non-proteinogenic amino acid linked to neurodegeneration".
On 26 March, Coulthart said that the disease "may be linked to environmental exposure" most notably "chemical exposures", and downplayed the likelihood of CJD. In a 5 May BBC report, Cashman said that one of the toxins to be investigated was beta-Methylamino-L-alanine (BMAA), a neurotoxin which is produced by cyanobacteria in marine, freshwater, and terrestrial environments. BMAA is currently the subject of scientific research for its potential role in a number of degenerative neurological diseases. Blue-green algae has been spreading in New Brunswick waterways. In her 27 October press conference, New Brunswick Health Minister Dorothy Shephard said that the NBPH report based on the enhanced interviews had ruled out blue-green algae, contaminated shellfish, and pesticides as potential causes for the mystery brain disease.
The findings of the NBPH epidemiological review, published on 26 October 2021, were based on 34 detailed telephone interviews by NBPH nurses from May to September. The report concluded that there were "no specific behaviours, foods, or environmental exposures that can be identified as potential risk factors with regards to the identified cluster of cases with a potential neurological syndrome of unknown cause". The NBPH webpage was updated to assure area residents that the investigation did not point "to algae blooms as being a potential source or cause of symptoms".
Cases In 2013, Marrero had requested CJDSS assistance in running tests on a suspected case of Creutzfeldt-Jakob disease (CJD) – an incurable, fatal disease. The results were negative. PHAC's CJDSS provided specialized expertise by interpreting diagnostic and providing autopsy results. The patient was retroactively identified as experiencing symptoms of the syndrome, according to NBPH. Marrero, who has since treated most of the 48 patients in the unknown disease cluster, said that he had detected "unusually young patients with progressive neurological symptoms in the Moncton and Acadian Peninsula areas" as early as 2013, according to a 28 October 2021 CBC News report.
On 17 March 2021 it was disclosed that "in 2019, 11 cases were discovered, with 24 more cases discovered in 2020 and another six cases in 2021". At the time, 42 possible cases had been tallied, and five people had died from the disease.
As of 25 April 2021, the cluster had been expanded to 47 possible cases. Of the 47, 37 were confirmed and 10 were suspected cases.
By April 2021, six deaths had been linked to the disease, but the NBPH said that "in some cases, additional information is needed to determine if the cause of death was a result" of the syndrome. The Department of Health restated the history at this time, as the first patient displayed symptoms in 2013 (instead of 2015 as had previously been reported) though that was deduced only in 2020.
According to a letter from Marrero to federal and provincial officials in February 2025, there were 507 patients suffering from unexplained neurological symptoms. 222 have been formally reported to NBHP.
Autopsy reports PHAC contracted a neuropathologist, Gerard Jansen, at the Eastern Ontario Regional Laboratory Association (EORLA) to perform autopsies on eight of the deceased. According to CBC News, Jansen said in May 2021 that he had diagnosed all five patients who had autopsies at that time and that he had "reviewed patient files for members of the cluster as part of his PHAC contract".
A 4 June New York Times reported that the Ottawa-based federal laboratory was conducting brain autopsies related to six cases "while a team of neurologists and pathologists from across Canada is reviewing the evidence". Times article reported on the brain autopsies and cited CJDSS director Coulthart, who said that the three autopsies were negative "for known forms of prion disease". The article said that the federal-provincial health authorities team included "neurologists, epidemiologists, environmentalists and veterinarians" and that "a team of neurologists and pathologists from across Canada" was "reviewing the evidence". In a 3 June CBC report, Vitalité director Natalie Banville, said that they did not have the results of the three autopsies at that time.
At the end of August, Jansen presented his autopsy results to the federal-provincial oversight committee, according to New Brunswick Health Minister Dorothy Shephard. On 7 October Jansen published the results of the eight autopsies on Canadian Association of Neuropathologists (CANP) website. During the 61st annual meeting of the CANP, Jansen presented his findings to 20 to 30 colleagues in which he suggested that the eight patients previously diagnosed with the novel neurological syndrome, "represent a group of misclassified clinical diagnoses", and that they "died from a variety of causes, including cancer, Lewy body dementia and Alzheimer's disease". The abstract said that "in these eight patients no evidence for a prion disease was found, nor novel pathology". The virtual meeting of the CANP was held from the 14 to 16 October. Soon after the meeting, Jansen's autopsy results were published by the media – whose sources are unknown – before family members, the PHAC, the OCHOH, or Marrero were consulted. Jansen told CBC that it was not "surprising" that neither Marrero nor PHAC seemed to support his findings or conclusions that the eight patients previously diagnosed with the syndrome of unknown causes, "represent a group of misclassified clinical diagnoses". New Brunswick Public Health requested Jansen's "final autopsy reports" in late September 2021 and received them by 24 September.
A November 2021 article in The BMJ reported that the results of the autopsies caused some to question the existence of New Brunswick's "novel neurological syndrome".
Geographic region As of April 2021, the syndrome had only been identified in the province of New Brunswick, with thirty-five cases in the Acadian Peninsula, eight cases in the Moncton region and one case of undisclosed origin.
The mayor of Caraquet said that the town was "trying to live normally, but everybody has that in the back of their mind".
Investigations