Multistep hypothesis

[Vivienne47]

I was diagnosed with ALS in 2022 age 63, with no family history. I am intrigued by the hypothesis proposed by my neurologist and his team in 2018 that it might be a multi-step process, with six triggers if there is not a genetic element, and fewer if an ALS gene is implicated. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105040/

I've been thinking about what might be my six triggers, and what I have done to try and fix. I would be interested in others thoughts on this.

1. Lumbar spine compression - I have two compressed discs at L2/3 and L4/5, not enough to compress nerves, but may be enough to set up inflammation in the lower spinal area (I have leg onset). FIX: I have treated this with IDD therapy. I am taking JuicePlus supplements which are loaded with antioxidants.
2. Hyper-metabolism. I was always a skinny child and have never had to worry about weight. Before my ALS symptoms started I dabbled with intermittent fasting for its reported heath benefits. Perhaps this tipped me over the edge of hyper-metabolism. I was advised by my neurologist NOT to diet and to gain a few pounds as plump people seem to do better with ALS. FIX: I eat lots now!
3. Calcium imbalance: I read that dying neurones are loaded with calcium. Just before my ALS symptoms started I was put on a very high dose calcium supplement after breaking a bone, and immediately I found myself feeling more unsteady in the garden. I was told this was not a known side effect so I kept on taking them, but I have stopped now, since my diagnosis.
4. Vascular insufficiency: I have had thread veins, varicose veins and also Reynaud's syndrome for a long time. I read that vascular leakiness is a possible causative factor in ALS. FIX: I am now being treated for Reynaud's syndrome with nifedipine.
5. Ancient viruses in our germ line. HERV-K is implicated in ALS. FIX: I am on the Lighthouse II clinical trial testing an HIV drug combo (Triumeq), and seriously hope that I am on the drug and not the placebo.
6. Liking for shellfish - they are known to have high levels of heavy metals. I hope this is not significant because I really don't want to give them up.

Staying hopeful that some of my 'fixes' are working. I have hardly progressed on the ALSFRS-R score since my diagnosis.

 

[Nikki J]

I don’t believe anyone can know what their triggers are. Everyone with SALS understandably wonders why this happened and looks for reasons

the step theory is no just for SALS btw. They believe that FALS has fewer steps and some of them are very common life events or exposures which is why some mutations are very highly penetrant. The whole theory is very complicated and uses logarithms to come up with their numbers. The most common highly penetrant quite early onset sod1 mutation is supposedly 2 steps. C9 very penetrant but older onset is three. TARDBP is four.

it is an interesting theory. studies of genetic carriers collect a lot of data on lifestyle and comorbidities looking for clues

i am glad you are slow progressing. Hope it continues

 

[rao]

Age is certainly one of the steps. another could be diet, if u constantly consume food with bmaa toxin you will very likely receive neuro damage which can lead to als. another is impact sports. funny i dont think i have any triggers apart from age (only 36 at dx) n that i got gout jus months before footdrop hmm... i have religiously drank this brand of tomato juice for 10 years almost a cup a day.... if that had some type of toxin then it got me

 

[KimT]

I do know they study cluster areas and I was born and raised in a cluster area. I've also lived on highly sprayed golf courses for the last 40 years. I played golf. I had two pretty bad head traumas. I also worked in a sick building and two others in that ONE building were diagnosed with ALS with many cancers from the same building. I've had a messed up gut for years and take a PPI which are known to mess up microbiome. So, I have a lot of risk factors if I believe what I've read. What I never had was smoking (but grew up in a house with four smokers, up North, where second hand smoke is terrible), was never in the service, and am female.
I've also thought about it. One scientist in my family thinks Lake Champlain (where I grew up) has such a terrible problem with blue green algae that they started warning people not to eat fish in the 90s.
I get heavy metal testing every other year (since 2015) that includes mercury. I'm very low in all the toxic metals and I'm a huge fan of seafood BUT I eat walk Alaskan salmon, sardines, and other "safe" fish. I'll have the occasional Mahi but not on a regular basis.

 

[duster]

I've not heard this particular theory previously, of course we all try to make sense of causation. Of the factors Vivienne references above, my dad had five, plus genetic predisposition. I would have the same five -- time for me to do more research into this.