Primary Lateral Sclerosis - Unicorn, Dragon or Other Mythological Beast?

Lauren Elman, M.D., associate professor of neurology at the Hospital of the University of Pennsylvania and Penn Medicine, discusses her research with primary lateral sclerosis (PLS), a rare motor neuron disease often mistaken for ALS. #PrimaryLateralSclerosis #JohnsHopkins www.hopkinsmedicine.org/neuro...
CHAPTERS:
2:15 PLS History
6:48 Natural History of PLS
14:31 Clinical Care in PLS
15:37 What’s needed to conduct PLS clinical trials?
18:06 Neuropathology of PLS
27:23 Consensus Diagnostic Criteria
35:32 Neurobiology of PLS
38:19 Genetics of PLS
39:03 Are ALS and PLS part of a spectrum of disease?
40:22 Biomarkers in PLS
43:34 Neuroimaging in PLS
47:24 Measuring PLS Progression
54:16 Clinical Trial Targets - Symptomatic
55:31 Clinical Trial Targets - Disease Modifying
1:03:20 Conclusion

[@salvadorhirth1641]

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]

Hi, I have PLS and this hypothesis is new to me at least for this disease. I will investigate.

[@salvadorhirth1641]

@@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 ")

[@salvadorhirth1641]

@@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.

[@soulcandy5758]

Do you know what is the primary difference between pls and als, it is very important for me, Thanks

[@crist388]

@@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.

[@rachelbranning484]

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.

[@johngallagher3732]

Hahaha Fawk off

[@Trigger-xw9gq]

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.