I am a caregiver to a family member who has PLS. She is roughly 5 years now from onset of symptoms. She was diagnosed 2 years ago ( after having had symptoms for 3 years). Her lower body symptoms are minimal. However the upper body symptoms have not progressed slowly as suggested. 2 years ago she was functioning very independently, driving, talking ( slowed and a little slurred but well). A year ago she could still feed herself and care for herself in every way (no longer driving) her speech was very inhibited by then but we could still understand most words. She lost her ability to speak at all about 4 - 4.5 years after first symptoms ( 1-1.5 years after diagnosis). She lost ability to care for herself in any capacity, ( shower, eat, etc) about 4.5 years in. She has refused a feeding tube and has lost significant weight and is very thin. She has lost her ability to suck through a straw ( that occurred suddenly at about 4.8 months) which limits most nutritional methods to spoon feeding using a tiny demitasse spoon ( she can barely open her mouth or chew, she masticates using her tongue) only pureed food or baby food. She drools all the time. She can no longer use her arms and hands at all and has constant pain in her arms and hands. This is a person who was fully functional 2 years ago.... I don't call that a slow progression. She has only a very limited ability to hold a stylus and type a few letters and the eye gazer has not yet been something that works for her so very shortly we expect to lose all ability to communicate. Without a feeding tube she will not survive much longer ( her choice of course). I am frustrated because I keep reading that PLS progresses slowly "often over decades" and thats all thats ever discussed, it doesn't always progress slowly and I wish there was more discussion on that.
Concerning the etiology of PLS, are there studies of the possible role of the expansion of trinucleotide repeats in PLS? Sometimes an inadvertent methylation of a cytosine in a CAG triplet, followed by spontaneous deamination of said cytosine, may transform it in thymine, producing then a stop codon ( TAG instead of the original CAG that codes for glutamine ). Perhaps the inadvertent formation of stop codons could produce smaller peptides that could mimic nuclear localization signal peptides that would allow the intrusion of neuron nuclei. Ribosomal slippage events inside mitocondrial DNA should also be investigated as a possible source of instructions to produce peptides which, in the event of reaching the cell cytoplasm, might account for neuronal degeneration.
@@jrqasar3110 In my first comment, I made a mistake because I was thinking about another diesese ( in Huntigton's there are intrusions in neurons nuclei, whereas in ALS and PLS, proteins that should remain in the neurons nuclei are exported to the cytoplasm, so instead of saying " ... that could mimic nuclear localization signal peptides that would allow the intrusion of neuron nuclei ", I correct it to " that could mimic nuclear export signal peptides that would allow the intrusion of neurons cytoplasm with Ataxin -2 ")
@@jrqasar3110 I suspect that, if the quantity of both DNA topoisomerases and DNA glycosylases could be increased in patients that carry expanded CAG repeats in both the Huntingtin and in the Ataxin genes, those diseases could be slowed down. Interleukins should be investigated as means to expand those enzymes.
@@soulcandy5758PLS has primarily upper motor neuron signs on exam, such as spasticity and hyperreflexia. ALS has both upper and lower (muscle wasting, fasciculations, hyporeflexia) motor neuron signs. Essentially they’re different based on physical exam findings, but the most typical cases of either diagnosis have notably different prognoses and the expectations for progression. You should speak with your doctor if you are suspecting this in yourself or someone else, or have more specific questions for you.
Great presentation. It’s unfortunate that the other male physicians kept interrupting you, and almost became hostile. We need more respect for women in medicine.
There was no “interrupting” nor hostility, there was merely genuine, legitimate, respectful comments & questions, and she was not bothered one bit, she even said that she appreciated the discussion! This is how scientific discourse works, but it sounds like what you want is a special protection from any inquiry whatsoever just because she’s a female! Typical oversensitive, man-hating modern-day feminist - the idea that we can make both sexes equal by focusing solely on the issues of one of them.
![I.N "HALLUCINATION" | [Stray Kids : SKZ-PLAYER]](http://i.ytimg.com/vi/n5B5q1Hwt_U/mqdefault.jpg)
I am a caregiver to a family member who has PLS. She is roughly 5 years now from onset of symptoms. She was diagnosed 2 years ago ( after having had symptoms for 3 years). Her lower body symptoms are minimal. However the upper body symptoms have not progressed slowly as suggested. 2 years ago she was functioning very independently, driving, talking ( slowed and a little slurred but well). A year ago she could still feed herself and care for herself in every way (no longer driving) her speech was very inhibited by then but we could still understand most words. She lost her ability to speak at all about 4 - 4.5 years after first symptoms ( 1-1.5 years after diagnosis). She lost ability to care for herself in any capacity, ( shower, eat, etc) about 4.5 years in. She has refused a feeding tube and has lost significant weight and is very thin. She has lost her ability to suck through a straw ( that occurred suddenly at about 4.8 months) which limits most nutritional methods to spoon feeding using a tiny demitasse spoon ( she can barely open her mouth or chew, she masticates using her tongue) only pureed food or baby food. She drools all the time. She can no longer use her arms and hands at all and has constant pain in her arms and hands. This is a person who was fully functional 2 years ago.... I don't call that a slow progression. She has only a very limited ability to hold a stylus and type a few letters and the eye gazer has not yet been something that works for her so very shortly we expect to lose all ability to communicate. Without a feeding tube she will not survive much longer ( her choice of course). I am frustrated because I keep reading that PLS progresses slowly "often over decades" and thats all thats ever discussed, it doesn't always progress slowly and I wish there was more discussion on that.
Concerning the etiology of PLS, are there studies of the possible role of the expansion of trinucleotide repeats in PLS?
Sometimes an inadvertent methylation of a cytosine in a CAG triplet, followed by spontaneous deamination of said cytosine, may transform it in thymine, producing then a stop codon ( TAG instead of the original CAG that codes for glutamine ).
Perhaps the inadvertent formation of stop codons could produce smaller peptides that could mimic nuclear localization signal peptides that would allow the intrusion of neuron nuclei. Ribosomal slippage events inside mitocondrial DNA should also be investigated as a possible source of instructions to produce peptides which, in the event of reaching the cell cytoplasm, might account for neuronal degeneration.
Hi, I have PLS and this hypothesis is new to me at least for this disease. I will investigate.
@@jrqasar3110 In my first comment, I made a mistake because I was thinking about another diesese ( in Huntigton's there are intrusions in neurons nuclei, whereas in ALS and PLS, proteins that should remain in the neurons nuclei are exported to the cytoplasm, so instead of saying " ... that could mimic nuclear localization signal peptides that would allow the intrusion of neuron nuclei ", I correct it to " that could mimic nuclear export signal peptides that would allow the intrusion of neurons cytoplasm with Ataxin -2 ")
@@jrqasar3110 I suspect that, if the quantity of both DNA topoisomerases and DNA glycosylases could be increased in patients that carry expanded CAG repeats in both the Huntingtin and in the Ataxin genes, those diseases could be slowed down. Interleukins should be investigated as means to expand those enzymes.
Do you know what is the primary difference between pls and als, it is very important for me, Thanks
@@soulcandy5758PLS has primarily upper motor neuron signs on exam, such as spasticity and hyperreflexia. ALS has both upper and lower (muscle wasting, fasciculations, hyporeflexia) motor neuron signs. Essentially they’re different based on physical exam findings, but the most typical cases of either diagnosis have notably different prognoses and the expectations for progression. You should speak with your doctor if you are suspecting this in yourself or someone else, or have more specific questions for you.
Great presentation. It’s unfortunate that the other male physicians kept interrupting you, and almost became hostile. We need more respect for women in medicine.
There was no “interrupting” nor hostility, there was merely genuine, legitimate, respectful comments & questions, and she was not bothered one bit, she even said that she appreciated the discussion! This is how scientific discourse works, but it sounds like what you want is a special protection from any inquiry whatsoever just because she’s a female! Typical oversensitive, man-hating modern-day feminist - the idea that we can make both sexes equal by focusing solely on the issues of one of them.