Every once in a while, some oddball treatment for difficult to treat diseases emerges. In my career, one example was the Zamboni treatment for multiple sclerosis, which took the MS world of patients, caregivers and some governments by storm, especially in Canada in 2009.
Paolo Zamboni was an Italian vascular surgeon who proposed the radical idea that MS was caused by obstructions of draining views from the brain and spinal cord, for which he proposed opening the veins by balloon catheters inserted into the affected veins and then inflating them.
His evidence was based on before-and-after graphic venograms illustrating blocked veins, opened up by surgery and patient claims that they were much better following the treatment — evidence which was compellingly impressive to patients, their families and some physicians.
And who could blame them? Treatment for MS was based on an autoimmune hypothesis for the disease, and while the drugs of the day reduced relapses somewhat, they barely touched the cumulative disability associated with MS. And as many patients and families from those days might recall, treatment wasn’t without troublesome side effects such as fatigue, in a disease already plagued with fatigue.
At the time, a colleague and I managed roughly 1,500 MS patients in northwestern Ontario working out of a clinic in Thunder Bay. It wasn’t long after a lot of publicity surrounding the effectiveness of the Zamboni treatment, especially in Canada, that some patients clamored to have the treatment, even if they had to travel abroad to find a surgeon willing to carry out the procedure and pay high bills in the process. Some provinces paid for the treatment and other patients were helped by communities who raised money to support the new treatment.
I met Zamboni twice and both times he was convinced he was right and keen to participate in clinical trials to prove his point. Unfortunately, later clinical trials failed to support his hypothesis and in no time, the Zamboni treatment disappeared into history, despite the initial widespread enthusiasm, especially in Canada, and claims by some patients that they were better.
Looking back, it was one of those perfect storms of patients desperate to find an effective treatment, someone like Zamboni who was equally desperate to help his wife and others with MS, the lack of any truly effective treatment and, I should add, more than a little arrogance on the part of some MS clinics, which failed to grasp how desperate some of their patients were and fed up with the then current treatments offered by MS clinics and pharmaceutical companies.
We may be about to repeat an equivalent crisis: millions of patients with dementia, especially of the Alzheimer’s type and their families are desperate to find an effective treatment to significantly slow, even stop, the progression of the dementia and perhaps, if given early enough before the earliest symptoms emerge, a low-risk treatment that might stop dementia from developing.
Unfortunately, despite the claims of pharmaceutical companies that this or that drug designed to clear the brain of beta amyloid (or these days, tau) no drug has been shown to meaningfully slow or stop cognitive decline in all its forms in Alzheimer’s — whatever the claims of the pharmaceutical companies.
The trouble is that the underlying hypothesis for Alzheimer’s based on the toxic accumulation of beta amyloid and tau in the brain may be wrong. Certainly both occur, and both can be reduced by treatment, but as Richard Feynman, one of America’s best theoretical physicists repeatedly pointed out, the most promising theory, if not supported by strong experimental evidence, is wrong.
And that’s the problem now in Alzheimer’s disease — the lack of robust evidence to support it.
Which brings me to a paper in Nature, one of the very best general science journals in the world, from August, titled “A Controversial Alzheimer Surgery is Getting A Closer Look” accompanied by the additional comment, “Jaw-dropping patient videos and miraculous testimonials ignited a frenzy in China over a technique that was said to reverse the symptoms of the disease. Now it is entering trials worldwide.”
The tone of the article takes me back to Zamboni days. So, what’s on offer here?
The surgical technique involves microsurgical methods to link lymphatic-like tributaries draining the brain with venous outflow from the brain for the purpose of enhancing drainage of beta-amyloid from the brains of patients with Alzheimer’s disease.
It sounds fanciful, but was tried by a Chinese microsurgeon in 2020 as a way of treating Alzheimer’s disease in an 80-year-old man. The results were documented by serial videos, which revealed a dramatic improvement from a man who before surgery “was slumped in his hospital bed, to days later, when he was alert and recognized his father, to by the eighth month … walking briskly and [being] able to recite a Maoist military anthem from memory.”
The videos went viral, as they say, and it wasn’t long before other microsurgeons in China were trying the same procedure and word got out to surgeons in the U.S., U.K. and elsewhere of this novel way of treating Alzheimer’s disease, possibly by facilitating amyloid clearance from the brain.
The trouble is that as exciting as the initial and hundreds of later similar operations (chiefly in China) were, there was a stunning absence of evidence. Only now, several years later, are suitable clinical trials underway to see whether the initial enthusiasm is justified.
The story is amazingly similar to the Zamboni story — surgical treatment of the drainage systems of the brain and the results will probably be the same.
The skill required to link up tiny lymphatics with views draining the brain would be a challenge for most surgeons, which why in China at least, most of the operations were carried out by “microsurgeons” — a terrible word, which some might mistake for tiny surgeons, but are surgeons trained in handing tiny vessels in complicated small spaces, hence presenting a real surgical challenge, unlike Zamboni’s opening up of much larger draining veins from the brain and spinal cord.
This case illustrates how enthusiasm for a procedure can spread internationally, in this case to mainstream hospitals such as the Cleveland clinic, with little concrete evidence that it works. Few of those Chinese patients were part of what would considered proper studies.
Let’s hope for clarity and, should it work, an explanation that makes sense for how it works.
Dr. William Brown is a professor of neurology at McMaster University and co-founder of the InfoHealth series at the Niagara-on-the-Lake Public Library.
