Alier Marrero is stumped.
For years, the neurologist in Moncton, New Brunswick, has seen patients with symptoms common to Creutzfeldt-Jakob disease, a fatal brain disorder that affects one in 1 million people each year.
But diagnostic testing for the rare neurodegenerative syndrome keeps coming back negative, more patients with similar symptoms have turned up each year, and Marrero hasn't found another cause. Federal public health officials last year identified the cases as a cluster meriting further investigation.
Now Marrero and scientists and doctors from Canada and around the world are playing detective in a medical whodunit, racing to untangle the cause of the brain disorder that has afflicted 48 people, six of whom have died, in the Moncton area and New Brunswick's Acadian peninsula.
Those afflicted with the condition - called the New Brunswick Cluster of Neurological Syndrome of Unknown Cause, for now - have ranged in age from 18 to 85. Symptoms began in 2018 and onward for many of them, but one case in 2015 was identified retrospectively last year.
"The suffering is immense . . . because it's beyond physical," said Marrero, who works at Moncton's Dr. Georges-L.-Dumont University Hospital Center. "There's also the neuropsychiatric and moral suffering of the patients that is only partially relieved by medications."
An otherwise healthy 75-year-old woman arrived at the Dumont emergency department last June. For months, she had experienced unexplained weight loss and what she described to her daughter as a "trembling sensation" inside her body. Her legs felt heavy. One arm was shaking involuntarily.
The daughter said her mother is one of the cases under investigation.
"My mother goes to bed at night and questions herself: 'Am I going to wake up tomorrow, and if I do wake up tomorrow, am I going to be able to walk or talk?'" she said. "Because there's no answers. Nobody knows anything. There's no reasoning. There's nothing."
Patients experience a constellation of symptoms, Marrero said, usually beginning with atypical anxiety, depression and muscle aches or spasms. They develop sleep disorders, including insomnia so severe that they sleep only a few nights a week or not at all, even with medication. Their brains are atrophied.
Many experience blurred vision, memory problems, teeth chattering, hair loss and trouble with balance. Some, including those in palliative care being administered strong medications, suffer from uncontrollable muscle jerks. Others have rapid and unexplained weight loss and muscle atrophy.
Some have hallucinations, including what Marrero said are "terrifying hallucinatory dreams" that leave them afraid to go to sleep, and tactile hallucinations in which they feel as if insects are crawling on them. One symptom, particularly devastating for loved ones, is Capgras delusion, a belief that family members have been replaced by impostors.
"The rapidity in the constellation of features is something that - I've not seen this before," said Michael Strong, the neurologist who heads the Canadian Institutes of Health Research.
The cluster was detected by the federal public health agency's Creutzfeldt-Jakob disease surveillance system, which monitors for CJD and other prion disorders. They occur when prions, misfolded proteins, build up and cause normal proteins in the brain to misfold. Under a microscope, the brains of people and animals with prion disorders resemble sponges with small holes.
Michael Coulthart, who heads the surveillance system, said it's notified of many suspected cases each year, but only a tiny number are confirmed. The system has identified 36 "definite and probable" cases of CJD in New Brunswick since 1998.
The system doesn't typically follow up on unconfirmed cases; the physician treating the patient is left to search for another diagnosis.