Brain worm!

A man went to the doctors complaining of a headache, strange smell sensations and fits. A worm in his brain was to blame...
01 December 2014

Interview with 

Andrew Dean, Addenbrooke's Hospital & Dr Hayley Bennett, Wellcome Trust Sanger Institute

AI-GENERATED-TAPEWORM

An AI-generated tapeworm

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A British man repeatedly visited his doctor complaining of headaches and experiencing strange smells that others could not detect. A lesion was visible in a brain scan. Surprisingly, though, it was mobile and, over several months vanished from one part of the brain and reappeared in another. Sara Sjosten went to speak to Addenbrooke's Hospital neuropathologist Andrew Dean and molecular biologist Hayley Bennett to hear how they made an unexpected diagnosis...

Andrew - Rather alarming features that came to life on his repeated MR scans were that the lesion that had started in one cerebral hemisphere appeared to be slowly wandering along into another hemisphere across the midline and into a deep part of the brain. It was clearly time to have another attempt to getting a tissue diagnosis of what his problem was.

Sara - So, you had this patient come in and he had all these disturbances. What did you do at that point?

Andrew - Back in 2012, presented with another piece of tissue by our neurosurgeons, definitely, something you don't see in East Anglia every day, a worm-like structure, which was at least a centimetre long and had features that would really suggest it was sort of tapeworm.

Sara - A tapeworm in this man's brain. This doesn't like a very promising thing to find.

Andrew - Definitely not good for him, but once it's found, at least, one can start to think of an appropriate treatment to kill the organism. The main aim, if you can't try and cut the lesion out and a lesion like this deep in someone's brain isn't very easy to cut out without producing severe damage, is to find out exactly what it is. Now, we know roughly what the class was going to be. However, I was interested to know if we could confirm the diagnosis using a molecular genetic means, which is certainly feasible, given that the worm was fortuitously quite separate from the rest of the inflamed brain. It was possible to take a microscope section, a glass slide, scrape off the bit of worm which would contain its DNA, extract that DNA, purify it up, and perhaps analyse it in terms of whether it could respond particularly well or badly to the standard medication against tapeworms.

Sara - In order to treat this patient, they needed to identify exactly which tape worm this was. I spoke with geneticist Hayley Benett who worked on this worm sample to identify the tapeworm.

Hayley - So, our part of the story was really when the pathology department contacted us with the sample and said, "We have this worm. We want to learn more about it." And we were really excited from the scientific point of view to get hold of the sample and sequence the genome of the worm.

We only had a very small amount of DNA to work from, 40 billionth of a gram. So, we really had to decide carefully what we were going to do with this DNA. First of all, we looked at a gene that is known as the bar code of life and we use that to confirm what exact species this worm was. And then we had some DNA left over. We were able to make what we call a sequencing library and sequence the genome. In this particular case, the rare infection, in our analysis, we took potential drug targets that we've already identified with other tapeworms. If that was still present in this rare worm, there might be a potential for drugs that develop for the more common worms to be cross applied and used for the rare infections.

Sara - But with this identification, could the man be treated?

Andrew - Information given back to the infection diseases, physicians allowed them to immediately start some drug treatment. He's been followed up for a couple of years now with fairly regular MRI scans. The most recent one which I think was a few months ago now showed that the lesion in his brain was largely quiescent. We are hoping therefore that he's been effectively cured.

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