In the beginning

I was healthy, never needing to see a doctor. Never would I have guessed or known anything about ms changing my life overnight, or what MS ever was.   I was 49, active, going out on camps into the wilderness areas with my partner. A drive to the ocean and camping the coast in remote areas was so much fun with Wil,  Going to Hot August Nights, camping, and going thru every isle of three separate Super walmarts to stock up on items not found in the small town we live in was part of the fun, along with walking the isles of the antiques and flea market vendor's, then going thru ever isles of cars displayed at every hotel.

Searching for the best spot to eat, we always made that  into a adventure. Geo caching came later, with even more spots found in remote locations on our travel paths, giving us different views of areas, and camping spots.

MS hit me hard in 2010, and keeps progressing.

It was late December, I took a Fall while walking to the customer service booth, to get cigarette for A customer.  A puddle of water was being hidden by another employee. He Watched me fall, but corp policy is not to say anything.. I fell hard. But needing a job, went back to my station as a cashier, scanning products as fast as possible.
A manager, took me to the side to file company papers, as a incident report, as he did not want to loose bonus for no accidents that quarter, since it was December 18th.

Within three months, I was holding onto the counter for support, my vision going double, gait was off, my wrist hurt, and then my hands froze up, dropping groceries.

  I never did see the video of my fall, that triggered MS, that they said  laid dormant in me.  I will spare the details of a broken workers comp system USA has, but lawyers are terrible, and cases drag on, without medical care.

The local bandage hospital we have in town initially splint up both wrist, gave me some strong pain killers, but noticed my leg dragging before leaving.  Referred me to a neurologist, as they had none, and I must see the company Dr.

Dr Quack, I call him yelled terribly at his patients. You had to see a company Dr, not one you chose. The best thing he told me, is "You have something going on, but they (the company) will not let me run any test to prove one way or the other"

My hands were clammy, doughy to the touch. Right side pain went to left side and crossed back. He told me, impossible, as the right brain doesn't talk with left brain. But something was not right.

Clonidine, a inexpensive blood pressure medicine was used off label. This unclenched my hands. He had me go off, titrated up and down, with results of hands clenching up, and being doughy.
But that worked.  I did not know it is a old drug used for MS off label.  a inexpensive drugs used for pain and inflammation.

A local Neurologist was seen. Another quack, as said I was fine, faking symptoms.  Even measuring electrical flow in my wrist, to say no issue, with warming or cooling wrist to obtain his results.  Not sure how you can fake symptoms physically seen, and what was going on.  Just knew body pain, wrist plain, and not being right.

A local GP was finally seen. Took six months to get the insurance company to approve a MRI.  In the meantime that year I was sent to a pain management Dr.  From opioid, up to Morphine was used. Initial diagnosed CRPS, "Chronic Regional Pain Syndrome", as they needed a diagnosis for pain med.  The local pharmacists asked me if I was picking up for someone on their deathbed, as the amount of morphine given.

 The local hospital used again.  MRI came back, read by the only person who reads every one's. No MS in big bold print. The Local country Dr  said they did not go far enough. Sent me to a Neurologist out of our little town.

  He looked at the film, yes before CDs, each film would be looked at.  Four were told to keep in order, and he scheduled blood test and a spinal tap in his office immediately.

These came back with ontological bands, the rest ruling everything out.

Treatment started with Copaxone.
Pain Dr weaned me off opioid and Morphine.  Cymbalta and Lyrica   were used in combination to treat Pain in Multiple Sclerosis.  The electrical zaps, Gabapentin and Nortriptyline.
 More about that in another blog though.

Guess this is a good starting point for my blog in hope to help others.

Thanks for reading.

For more go to my blog everchangingms.blogspot.com

Thanks for reading
 Joe

Botox, OnabotulinumtoxinA

I would never think a procedure would be in your mind, as one to look forward to.

But Botox, or  OnabotulinumtoxinA t is used o treat dystethia, or muscle stiffness, muscle cramps, spascisity, walking problems, movement problems.  
A treatment which people with Multiple Sclerosis get.

Botox can be used to treat many symptoms associated with multiple sclerosis. Patients who have spasticity affecting their arms or legs may be good candidates for botulinum toxin injections to relieve painful spasms and improve mobility.

I have had botox treatments since being diagnosed  of multiple sclerosis. I had maxed out  baclofen  early on. My Neurologist, was a old timer, with no computers. He worked as a stand alone neurologist, with a staff of two office gals, one who did your appointmens, in her hand written book.  She had your paper file for Dr to go thru, ready for him.. The other gal had a real old computer, she could obtain the necessary forms on, and Bill the insurance. I am sure another gal took down info for billing outside of his clinic.

He used the old time scrypt, decypherable by him and a few Drs I talked with. Looked like scribble marks, but so does shorthand.  Dots of injection sites, other records were transcribed, like the sleep study.  EMG, was always followed up on how fast nerves responded. Record keeping in each patients file, as Dr would do before electronics came out.

A fax machine was used to fax prescriptions, but the new pharmaceutical companies did not like.  The neurologist would fill my Gabbapentin and Provigil.  I found a way around this by sending in original prescriptions for mail order to them, as faxes kept getting lost, or the insurance company would say, we've tried to contact your Dr multiple times, with no response. This happened by the insurance computer calling at 2am, not saying what was needed from the dr. It became a a problem for his staff, their limited time, and hours listening to messages, and hours I spent trying to find where the problem was. It was the insurance companies computer not recognizing the Drs Faxes.

There were a couple other part time gals, who ran the emg machine, sleep study, and other test.I

Botox works by blocking the release of acetylcholine from nerve endings. Acetylcholine is a neurotransmitter required by muscles for muscular contraction. By eliminating the ability of a muscle to contract, it relaxes, thereby decreasing spasticity and tone.

Spasticity is a condition in which muscles exhibit almost constant contracture or activity, leading to loss of range of motion, decreased function, and even pain.

Spasticity occurs after an area of the brain or spinal cord has been injured, leading to weakness and increased tone.

When an arm or leg which is affected by spasticity is moved by an examiner, there is involuntary resistance to that movement.

Often, this spasticity is made worse when the speed (or velocity) of the movement increases.

Spasticity is often seen after a stroke, traumatic brain or spinal cord injury, or in cases of multiple sclerosis.

In some cases, spasticity can be associated with development of involuntary tremors.

The blockade of acetylcholine does not occur immediately. Most patients do not begin to see the effect of a botulinum toxin injection for a few days, and it may take a few weeks for the maximum benefit to become apparent.

This neurologists was quite informed on latest developments, what was working, and what did not.  He could do a spinal tap right in his operating room, and send labs out, have results quickly.

This he did with my botox injections every three months, as that's all the insurance would pay for is every three months. My botox lasted 62-64 days, I would record in my book I brought in.  Botox day was describing muscles inside the leg, or outside ones. This would include stiff muscles in the neck, Charlie horses.
Or how the toes were curling in our out.
He knew where to inject the botox, the debth, and feel the muscle spasms.

Three weeks later was the follow up, where he would ask me what was in my book note book of questions, comments, and research. I had done.  A question answer period, sometimes a booster shot for botox, but lots of questions answered, and items to try to help.

Botox has a Black Box  warning.
From their site"

https://m.youtube.com/watch?v=4x9yRjrN0iQ

IMPORTANT SAFETY INFORMATION

BOTOX® may cause serious side effects that can be life threatening. Get medical help right away if you have any of these problems any time (hours to weeks) after injection of BOTOX®:

Problems swallowing, speaking, or breathing, due to weakening of associated muscles, can be severe and result in loss of life. You are at the highest risk if these problems are pre-existing before injection. Swallowing problems may last for several months

Spread of toxin effects. The effect of botulinum toxin may affect areas away from the injection site and cause serious symptoms including: loss of strength and all-over muscle weakness, double vision, blurred vision and drooping eyelids, hoarseness or change or loss of voice, trouble saying words clearly, loss of bladder control, trouble breathing, and trouble swallowing

The black box warning continues an can be read at botox.com

BOTOX® may cause loss of strength or general muscle weakness, vision problems, or dizziness within hours to weeks of taking BOTOX®

The dose of BOTOX® is not the same as, or comparable to, another botulinum toxin product. .

Other side effects of BOTOX® include: dry mouth, discomfort or pain at the injection site, tiredness, headache, neck pain, eye problems: double vision, blurred vision, decreased eyesight, drooping eyelids, swelling of your eyelids, dry eyes; and drooping eyebrows.

For more information refer to the Medication Guide or talk with your doctor.

My Neurologist went on a "medical leave" just before botox was to be injected. This left me with the last injection being August 2019. My calves were tight, hard as rock before I was able to see a new Botox Neurologist. His First opening being late February 2020

The University Hospital used a EMG guidance computer to assist the neurologists and his student. A special chair to sit it that allowed easy access to multitudes of muscle names the Neurologist rolled off as he injected The multitude of sites.  The machine had sound, I could not see the graph. I just knew he was injecting the proper muscles and depth, from having them from old neurologist.   Both calls were hard as rock, some pulling on toes, or the top and bottom of the foot. This causes a lift problem with the foot.

My neck muscles had spasmed extensively. These muscles control the arms, which had signs where muscles were pulling you could see the indent near the elbow. Muscle names rolled off the Drs mouth as injections went deep into the muscle. I recognized the trapeze muscle, controlled by the neck, but had no idea of the names, or how deep these other muscles were. These were all injected into the neck location, on both sides.  The Doctor was more complete with more botox used into all the problem areas.

I will see him back in three months, keeping track in my book, of side effects, 

helpful and hopeful for great results.

I hear it helps for migranes and more.

Have you had Botox? And your story?  Chime in!
Cheers
JoeY

Multiple Sclerosis DNA

                                       Photo of gene from wikipedia.org


Multiple Sclerosis blog of DNA Technical reading.

I did a 23and me home testing.
If you did a health dna, this will show up under celiac diseases.
It may take some reading, and researching, but this will show up.
The HLA-DRB/DQA gene

There are links to folllow, but for less confusion, just Google the gene.
there are many variants I show below, having a complete DNA done of me. Everybody may be different, but hope this helps science.

https://ghr.nlm.nih.gov/gene/HLA-DQB1#conditions
https://ghr.nlm.nih.gov/gene/HLA-DQB1#conditions

Look up on Google this gene, and look under auto immune disorders

HLA-DQB1 gene

major histocompatibility complex, class II, DQ beta 1

Normal variations of the HLA-DQB1 gene have been associated with several additional disorders. Most of these disorders have an autoimmune basis, which means they occur when the immune system malfunctions and attacks the body's own tissues and organs. Autoimmune disorders that have been associated with HLA-DQB1 include multiple sclerosis, pemphigus, and type 1 diabetes (described below).

Multiple sclerosis is a chronic disorder of the brain and spinal cord (central nervous system) that causes muscle weakness, poor coordination, numbness, and a variety of other health problems. Several variations of HLA-DQB1 appear to increase the risk of developing this disorder. One of these variations, HLA-DQB1*06:02, is the same version of the gene that increases the risk of narcolepsy.

Some evidence suggests that the HLA-DQB1 gene may also play a role in several forms of pemphigus, a condition that causes severe blistering of the skin and mucous membranes (such as the moist lining of the mouth).

It is unclear how different versions of the HLA-DQB1 gene influence the risk of developing autoimmune disorders. These disorders typically result from a combination of multiple environmental and genetic factors. Changes in other HLA and non-HLA genes, some of which remain unknown, also likely contribute to the risk of developing these complex conditions.

23and me

We detected a variant linked to the HLA-DQ8 haplotype.doing

                                                    Photo from wikipidia.org

https://en.m.wikipedia.org/wiki/HLA-DQB1

https://en.m.wikipedia.org/wiki/HLA-DQB1

Multiple sclerosisEdit

Certain HLA-DQB1 alleles are also linked to a modest increased risk of multiple sclerosis.^[11][12]

See scientific details
I am not a doctor, or scientist, just researching, trying to understand the aspects of Multiple Sclerosis is having on me, and the commonalities this disease has of raging they my body.

Further investigation shows these SNP I have.

SNP : rs12487066

SNP : rs312993

SNP : rs3135388

SNP : rs6897932

SNP : rs7326018



Technical Report for these genes from DNA done 12/2019

SNP : rs12487066

Gen o Región : 3q13.11

UserSNP usedGenotypeAdjusted Odds Ratio*lrs12487066CT0.97

Multiple sclerosis has a clinically significant heritable component. It was conducted a genome-wide association study to identify alleles associated with the risk of multiple sclerosis.

It was used DNA microarray technology to identify common DNA sequence variants in 931 family trios (consisting of an affected child and both parents) and tested them for association. For replication, we genotyped another 609 family trios, 2322 case subjects, and 789 control subjects and used genotyping data from two external control data sets. A joint analysis of data from 12,360 subjects was performed to estimate the overall significance and effect size of associations between alleles and the risk of multiple sclerosis.

A transmission disequilibrium test of 334,923 SNPs in 931 family trios revealed 49 SNPs having an association with multiple sclerosis (P<1x10(-4)); of these SNPs, 38 were selected for the second-stage analysis. A comparison between the 931 case subjects from the family trios and 2431 control subjects identified an additional non-overlapping 32 SNPs (P<0.001). An additional 40 SNPs with less stringent P values (<0.01) were also selected, for a total of 110 SNPs for the second-stage analysis. Of these SNPs, two within the interleukin-2 receptor alpha gene (IL2RA) were strongly associated with multiple sclerosis (P=2.96x10(-8)), as were a non-synonymous SNP in the interleukin-7 receptor alpha gene (IL7RA) (P=2.94x10(-7)) and multiple SNPs in the HLA-DRA locus (P=8.94x10(-81)).

Bibliography

International Multiple Sclerosis Genetics Consortium. Risk alleles for multiple sclerosis identified by a genome-wide study. N Engl J Med. 2007 Aug 30;357(9):851-62.

SNP : rs3129934

Gen o Región : C6orf10

UserSNP usedGenotypeAdjusted Odds Ratio*rs3129934CT0.97

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with an important genetic component and strongest association driven by the HLA genes.

It was performed a pooling-based genome-wide association study in which Comabella et al. described eight SNPs validated in Spanish Caucasian cohort and US Caucasian cohorts. The most significant association was obtained for SNP rs3129934, which neighbors the HLA-DRB/DQA loci. Said SNP is associated with an increased risk for multiple sclerosis. The OR was 3.0 (CI: 1.8-5.0; P = 1.4×10(-5)).

Another studied polymorphism was rs7326018 which is one of the eight SNPs associated with increased risk for multiple sclerosis. Its OR was 1.8 (CI: 1.1-2.9, p = 0.0228).

Bibliography

Comabella M, Craig DW, Carmiña-Tato M, Morcillo C, Lopez C, Navarro A, et al. Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms. PLoS One. 2008;3(10):1–9.

SNP : rs3135388

Gen o Región : 6p21.32

UserSNP usedGenotypeAdjusted Odds Ratio*rs3135388GA1.81

Multiple sclerosis has a clinically significant heritable component. It was conducted a genome-wide association study to identify alleles associated with the risk of multiple sclerosis.

It was used DNA microarray technology to identify common DNA sequence variants in 931 family trios (consisting of an affected child and both parents) and tested them for association. For replication, we genotyped another 609 family trios, 2322 case subjects, and 789 control subjects and used genotyping data from two external control data sets. A joint analysis of data from 12,360 subjects was performed to estimate the overall significance and effect size of associations between alleles and the risk of multiple sclerosis.

A transmission disequilibrium test of 334,923 SNPs in 931 family trios revealed 49 SNPs having an association with multiple sclerosis (P<1x10(-4)); of these SNPs, 38 were selected for the second-stage analysis. A comparison between the 931 case subjects from the family trios and 2431 control subjects identified an additional non-overlapping 32 SNPs (P<0.001). An additional 40 SNPs with less stringent P values (<0.01) were also selected, for a total of 110 SNPs for the second-stage analysis. Of these SNPs, two within the interleukin-2 receptor alpha gene (IL2RA) were strongly associated with multiple sclerosis (P=2.96x10(-8)), as were a non-synonymous SNP in the interleukin-7 receptor alpha gene (IL7RA) (P=2.94x10(-7)) and multiple SNPs in the HLA-DRA locus (P=8.94x10(-81)).

Bibliography

International Multiple Sclerosis Genetics Consortium. Risk alleles for multiple sclerosis identified by a genome-wide study. N Engl J Med. 2007 Aug 30;357(9):851-62.

Gregory SG, Schmidt S, Seth P, Oksenberg JR, Hart J, Prokop A, et al. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet. 2007;39(9):1083–91.

SNP : rs6897932

Gen o Región : IL7R

UserSNP usedGenotypeAdjusted Odds Ratio*rs6897932CC1.06

Multiple sclerosis is a demyelinating neurodegenerative disease with a strong genetic component.

Previous genetic risk studies have failed to identify consistently linked regions or genes outside of the major histocompatibility complex on chromosome 6p. There is a study in which was described the allelic association of a polymorphism in the gene encoding the interleukin 7 receptor alpha chain (IL7R) as a significant risk factor for multiple sclerosis in four independent family-based or case-control data sets (overall P = 2.9x10(-7)). Further, the likely causal SNP, rs6897932, located within the alternatively spliced exon 6 of IL7R, has a functional effect on gene expression. The SNP influences the amount of soluble and membrane-bound isoforms of the protein by putatively disrupting an exonic splicing silencer.

This gene encodes a protein called alpha-IL7R. This protein plays an important role in how two growth factors (IL-7 and TSLP) affect specialization and maintenance of various immune cells.

IL7R-alpha protein can take two different forms. One way is anchored in the membranes of immune cells, while the other form is released by the cells into the bloodstream. The relative amounts of the two forms can affect the signalling amount mediated by IL-7 and TSLP, and therefore change their action on the immune system. Rs6897932 allele (C) increases the amount of free IL7R-alpha.

Since multiple sclerosis could be seen in autoimmune diseases, it makes sense that a SNP in a protein involved in the immune system would be associated with the disease. Furthermore, it has been observed that IL-7 signaling is altered in such patients.

Changes in IL-7 signaling could lead to the development of multiple sclerosis in several ways: through spontaneous reactions in immune cells and decreasing the ability to defend them, favouring chronic infections.

Bibliography

Gregory SG, Schmidt S, Seth P, Oksenberg JR, Hart J, Prokop A, et al. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet. 2007;39(9):1083–91.

Lundmark F, Duvefelt K, Iacobaeus E, Kockum I, Wallström E, Khademi M, et al. Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. Nat Genet. 2007 Sep;39(9):1108-13.

International Multiple Sclerosis Genetics Consortium. Risk alleles for multiple sclerosis identified by a genome-wide study. N Engl J Med. 2007 Aug 30;357(9):851-62.

SNP : rs7326018

Gen o Región : 13q31.3

UserSNP usedGenotypeAdjusted Odds Ratio*rs7326018TT2.09

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with an important genetic component and strongest association driven by the HLA genes.

It was performed a pooling-based genome-wide association study in which Comabella et al. described eight SNPs validated in Spanish Caucasian cohort and US Caucasian cohorts. The most significant association was obtained for SNP rs3129934, which neighbors the HLA-DRB/DQA loci. Said SNP is associated with an increased risk for multiple sclerosis. The OR was 3.0 (CI: 1.8-5.0; P =1.4×10(-5)).

The rs7326018 polymorphism is one of the eight SNPs associated with increased risk for multiple sclerosis. Its OR was 1.8 (CI: 1.1-2.9, P = 0.0228)

I hope this Technical report will be useful, and would love feedback from scientist, Drs, or you, exploring genes related to Multiple Sclerosis, and if others are coming up, or I will add to this page when other genes from DNA are found.

Cheers
JoeY