Thank you, pegleg, . . . indeed Parkinson's and Amyotrophic Lateral Sclerosis have many similar symptoms; both affect the motor nervous 'system' . . . but the 'dopamine' rather than 'glutamate' neurons are affected in Parkinson's. Advances in medical or biological science may help heal both disorders.

Thelma is one of my favorites, I only wish they would post more!

One of neurology's biggest problem is insufficient precision, . . . is the data sufficiently precise the conclusion validly follows therefrom? Such is the problem I think in the case of the question of whether females are at greater risk if they develop the disorder, even though they are believed to have a significantly lower risk incurring Amyotrophic Lateral Sclerosis. :Sigh:

There appear to be at least fourteen cases who have used the pacer and exceeded 'ten years alive' post-symptom onset . . . so far, . . . many remain candidates thereto . . . the expected number is seventeen (10% of patients are expected to reach ten years).

update
 

One of the standards for including a case in statistical calculations is completeness of the needed case. I counted forty-seven cases (from data patients provided on the web) this weekend who are either on a trach or passed away and left complete data for the basics . . . twelve bulbars and thirty-five limb onset . . . thirty-five is approximately two pilot samples (. . . 2x16 patients or 32 patients . . .). Of these thirty-five, two _probably_ are limb onset and another may not have correctly specified their onset date. Whether thirty-five or thirty-three, the median survival is seventy or seventy-four months, respectively. Regarding the possibly inadequately specified onset date, the patient is in the weaker half of the sample and correction, if appropriate, would move them well into the stronger half of the sample and therefore would only strengthen the median for the set. The bulbar median is under review will be further discussed in this thread (there are at least 56 but only twelve pacing and without missing completion data - hence we do not yet have a pilot sample):

http://neurotalk.psychcentral.com/thread224801.html

In principle, pacing patients should be more valuable in clinical studies because the researchers could collect dEMG data from them:

Identification of unexpected respiratory abnormalities in patients with amyotrophic lateral sclerosis through electromyographic analysis using intramuscular electrodes implanted for therapeutic diaphragmatic pacing

http://www.americanjournalofsurgery....598-4/fulltext

In the aforereferenced paper Dr. Onders provides more insight into patients of the original study.

Evaluations including all cases will likely show lower results because they always include all the least successful cases and remain in wait for completion data from those who continue advancing. Early studies are more likely to include patients who are later in the disease process because the treatment was not available to them before they were eligible. As time goes on, patients in the vicinity of a new implant site will be increasingly likely to receive timely implant.

Dehydration . . .
 

Dehydration:

https://en.wikipedia.org/wiki/Dehydration

How might the highlights be made in the case for ALS patients?

early posts re: pacer, astrocytes
 

Electrical device allows paralyzed man to breathe
http://web.archive.org/web/200503061...ML/000662.html

Acetylcholine neurons - the ones that contact the mucle
http://web.archive.org/web/200311031...ML/002172.html

Its hard to believe I am approaching my sixteenth 'anniversary' since formally engaging the ALS 'battle.' I was indirectly involved years before because the research area where I work can help many individuals, including those with ALS. According to the rules, six to seven years are required to validate a new molecule for treatment in a particular disease but numerous "Big Pharma" types have publically advised aspiring scientists they will need at least ten to fifteen years: if they are lucky. At present, as the DiPALS study evidences, the pacer is not yet ready for a Phase III study but how far away are we? Thankfully patients may obtain the pacer via the HUD/HDE but what about the guidance physicians and patients need on perfecting the timing or elucidating the therapeutic value seen in the report of Dr. Onders in last year's American Journal of Surgery? Bad medicine can save time but good medicine can save lives! The question whether there is a case against the pacer is of course an important one; I often review the cases I have discovered to appraise whether the weakest cases can be selected, and construed as a pilot study - are there inferences validly drawn therefrom working against the treatment? The ordinary media can make the task more difficult by failing to be careful in its choice of words. We still need to work on the question of 'it seems to work in many cases but why?'

Indeed, why do people get ALS to begin with?

At present, I am not sure whether those who would pursue a case against the pacer deserve 'a turn at bat' and I will develop this thought later but I wanted to point out the significance of Dr. Onder's paper as a showing of a de-facto biomarker, or even better than a biomarker. The ability to read the diaphragm's EMG signals live and continuously for long periods of time ought to make efficacy studies less expensive and faster to achieve preliminary insight as to prospective molecule's value. Patients may find they could enter studies based on the extent of the involvement of their diaphragm muscles and whether they are using the pacer as satisfying entry criteria . . . such can be a little better than the 'recently 'diagnosed'' standard; I shall also try to explain why such ought to be so.

I wish to restate an important point, . . . pacing ALS patients ought to be valuable in medical research studies even if they are not freshly diagnosed. Where their diaphragm remains unaffected or the impact has begun but the impact is not extensive, researchers ought to find ALS patient candidacy for studies valuable even if the study is not directed at the ALS patient because the data obtainable from dEMG may show evidence valuable in their immediate research interest or valuable to ALS researchers if the dEMG data shows some affect on the ALS disease processes.

Experts Hack for Lyme Disease Solutions in Boston and Berkeley
 

Experts Hack for Lyme Disease Solutions in Boston and Berkeley

https://www.morningstar.com/news/pr-...-berkeley.html


Lyme disease is often portrayed as 'falsing' the symptoms of ALS and those who try to determine whether they have Lyme disease are often frustrated the tests for Lyme are not very reliable.

see also:

Hacking Lyme Disease
https://www.massbio.org/news/blog/ha...disease-122003

I thought this event already happened . . . :

Lyme Innovation: Three Day Hackathon Jun 17-19, 2016
http://lymeinnovation.org/upcoming-events/

Although it probably will not stay there, for the first time the set of patients I am following achieved sufficient days to exceed the 'maximum' life expectancy . . . the data set has deficiencies such as inadequent date specifications and patients who have not been heard from in a long time. I detected several of these long lost cases recently; although most did not change the data much, some did. I am currently reviewing the data set from the point of view of 'false positive' . . . the chance these results are 'false positive' is? . . . I expect it to be small, I am hoping it will be smaller than one would likely guess.

Discovered Charley remains with us:

http://iydlify.blogspot.com/

due to post dated April 23. Was implanted in 2009.

gastronomy tube . . .
 

I remember a paper referring to a study in Scotland regarding the gastronomy tube and very high death rate of 25% and then remembered the Scottish games, wherein one event involves individuals tossing around telephone poles. The higher death rate might well be linked to larger size of Scottish people, though the report might not have indicated same. Never the less, as I would suggest, not only should ALS patients tone down the jogging, avoid, too, the caber toss until an ALS cure is found and you have full recovered.

Caber Toss
Scottish Heavy Athletics - Caber Toss

old news story . . . note comment at end of story
 

Diaphragm Pacing May Be Harmful in ALS

Diaphragm Pacing May Be Harmful in ALS | Medpage Today

Brief update on 'whole' set of cases . . . about 160 . . .
 

At least 100 cases reached more than the upper level life expectancy; forty-seven continue to be approaching but many of these are without a contact in quite a long time. Seventy-four have been discovered to have passed away. Many cases remain without complete data for complete analysis. At least 67% or two-thirds of the patients whom I have found providing data on the web have exceeded the upper level life expectancy where only about 20% were expected to do so . . . thus much bias must be found in order to challenge the efficacy 'claim' this set is representing. The more recent cases seem to be doing better . . . possibly because patients obtain their implant nearer the optimal point in the disease's course. We should remind ourselves the symptoms may belong to more than one actual disease and plausibly the pacer doesn't help with every one of them. Further research is needed to find 'fault-lines' to help us ascertain the basis for benefit and, if there are case types the treatment will not benefit then how to detect them, especially if there are cases where the treatment might cause harm.

Sorry to have been away for a while; unexpected circumstances. Priority one is updates. . . .

Operative Range of Diaphragm
 

Given your FVC, how 'healthy' must your diaphragm be in order to be pacer-eligible?

Operative Range


This is quick edition of table I continue to be working on.

Note: the diaphragm may be in any condition from 100% to 0%, fully to unresponsive to simulation in the 85% - 45% FVC range authorized for consideration of pacer implant.

Barriers of the bureaucracies . . . news soon . . . .

New Chart . . .
 

{not to scale}

Hypothetical Benefit

Patients need data tsunami . . .
 

Note Figure 1 of

Noah Lechtzin, MD MHS

Respiratory Effects of Amyotrophic Lateral Sclerosis: Problems and Solutions

http://www.aamr.org.ar/secciones/kin...tos_respir.pdf

shows about five to ten data points per patient in Figure 1, but dEMG technology is the most promising method of today:

Onders, et alia's Figure 1 of:

Identification of unexpected respiratory abnormalities in patients with amyotrophic lateral sclerosis through electromyographic analysis using intramuscular electrodes implanted for therapeutic diaphragmatic pacing

http://www.americanjournalofsurgery....598-4/fulltext

promises megabytes . . . and may well produce medical science basis as good as or maybe even better than biomarkers. :Wheel:

New hypothetical benefits spreadsheet shows diaphragm ranging data; the pacer may enable advancement in the scientific understanding of respiratory muscles, allowing more general deployment of the treatment in medical research - Barbara Brenner advocated unsuccessfully for. When clinical trial protocol is established, getting live change to be made thereto is very difficult, if not impossible because of potential legal repercussions due to non-perfected assessments of risks to patients and sponsoring organization(s). There may be some chance of permitting the involvement of some of these type of patients in every new clinical study but advocacy is likely needed. Essentially such was where Barbara Brenner's (BBZinger) efforts were going. "Per protocol" keeps risks in the 'channel,' violating protocol can disrupt the legitimacy of the clinical trial. Such risk can be very difficult to assess.

The orange highlight is added because I discovered, in 'my' downloaded version of the DiPALS trial report patient FVC needed to be 75% or less in order to be admitted to the trial. Thus twenty-five percent of the eligible patients per the FDA protocol were not allowed to enter the trial. The twenty-five percent excluded tended to be the strongest candidates. Of course this would have an considerable negative impact on the summary statistics for the trial.

Hypothetical Benefit

Resistance may continue to be experienced by pacing patients in participating in trials but there is likely no scientific legitimacy thereto because such patients would likely help the clinical trail obtain early indication of trial's sought after result, especially if the impact of ALS on the respiration muscles is studied to the point of perfecting such knowledge.

I have not received news from any patient regarding use of creatine and pulmonary pacing . . . creatine has not been helpful to ALS patients but might be helpful to pacing ALS patients.

A new MAUDE report involving non-ALS patient who used the device for more than two years appears in the FDA MAUDE database as received Jul 19 bu FDA.

VICE on HBO: Angelina Fanous' Debrief on Living with ALS
 

VICE on HBO: Angelina Fanous' Debrief on Living with ALS

VICE on HBO: Angelina Fanous' Debrief on Living with ALS - YouTube

re: life expectancy guesses . . . :
 

Life expectancy is often misunderstood and similarly often incorrectly represented. The 'official' quote once was 1-3 years for bulbar onset and 3-5 years for limb onset, now they more often say 2-5 years without mentioning onset. Numerous studies, however, have shown typical patients have less than a fifty-fifty chance of making three years from symptom onset, even in limb onset ALS. When they mention the life expectancy numbers they are almost always talking about averaged survivals from DISEASE ONSET to death: not diagnosis. Because some patients live quite a long time they tend to draw such average up much more than those with 'fast regression' draw the average down. Since they are around longer they are more likely to be detected surveys and therefore included in new calculations, too. The mid-point of limb onset tends to be about eight months longer than the mid-point for bulbar onset yet neither produces reliable predictions (medians not means). Most scholars consider remaining life expectancy nearly impossible to predict. There are positive and negative co-factors but exceptions are found to be numerous. Patients are wise to live each day as though it would be their last. Perhaps unsurprisingly, patients who are theologically active often appear to live longer. The difficulty of predicting life expectancy is one of the most problematic components of clinical study design.

re: Welcoming Jim
 

I removed Mr. McFarland from the bulbarians table because, as you can see from their more recent video, his voice remains strong but obvious signs of ALS remain . . . hence he belongs in the limb onset group:

JIM MCFARLAND needs "YOUR" help to WIN his ALS battle! | Medical Expenses - YouCaring

I have nearly completed the update of the data from patient web disclosures and the case favoring the pacer continues to strengthen; given the findable cases efforts to make even a preliminary case against the pacer will likely only produce very weak and vulnerable case . . . one of the biggest difficulties I am working on at the moment is many patients have not indicated their onset date and the result makes their status a problem of weighing estimation algorithms. In many cases patients can be determined to have a favorable status based on the rest of the available information they apparently provided where they appear very successful but when cases are close calls the issue is quite difficult to decide. There are about 57 of about 180 cases where onset date is not indicated. Although there are many remarks looking for a +16 month improvement there are many cases closer to a +6 month improvement. Dr. Onders apparently gave a speech in Athens recently (December, 2015):

ALS Worldwide In Athens, Greece: Recording
ALS Worldwide In Athens, Greece: Recording | ALS Worldwide

where he reported more than 1500 implants are completed; the previous report of this kind was given in Canada, where he reported in October of 2014 over 700 implants were completed. Of course many more cases were prognosed than underwent implantation. I hope to have some kind of outline of a summary statement posted here by Monday, August 22, 2016. Thank you for your patience.

Quick note . . . :
 

Original claim of 16 month improvement in average survival increased to 19.7 months and then 20.9 months, has reached 22 months (apparently reported yesterday) and I expect further improvement will develop as patients reach the operating room closer and closer to the temporally optimal 'window' for pacer implant. Since 'average' in ALS is almost always significantly higher than median, most patients will experience weaker than average benefit but substantial plurality ought to exceed same and the average, in my opinion, will likely continue to increase. It remains too early to tell how typical patients will benefit and some might not have, however, the Bulbarian's table shows at least six month improvement may be possible for most patients. Patients suffering fast regression or whose onset is near the lower motor neurons of the pulmonary system may not benefit much from the treatment. I will elaborate on this issue in future posts. The course of regression remains so difficult to predict most continue to maintain such is impossible to do:o.

Two quick points . . . :

At present, of the 175 patients who have disclosed pacing data via the web, 102 have exceeded three year life expectancy, more than 58%, whereas ordinarily less than 50% would be expected to do so. There are 67 cases who did not include their onset date.

At present, of 100 patients who have disclosed pacing data via the web, where their data is sufficiently complete, 45 have exceeded five years . . . 55 have not done so but of these 11 may still do so. The expected number of patients exceeding five years is about 20% . . . far less than 45%.

brief computer moment . . . :
 

There are an estimated 100,000,000,000 neurons in the human connectome; a synapse is a connection from one of them to another, therefore:

99,999,999,999:99,999,999,998 might identify a synapse were there only one synapse possible per pair of synapses. But there could be more than one. Since there are a few quadrillion synapses, storage holding a number like 9,999,999,999,999,999 ought to be able to able to be enumerative of them.

99,999,999,999:99,999,999,998;9,999,999,999,999,99 9 ought to be sufficient to store an identification for each synapse (fifty-one digits) - with the hope of whether one could reliably enumerate a specific neuron's synapses. Such might not be possible, however the following elaboration relies thereon:

Fifty-one digits is sufficient to identify each of the quadrillion synapses and a list containing all the synapses would be fifty-one quadrillion bytes long. We will only need to place one digit in one byte at this time. In order for representation of each synapse to be stored as implied above, we will need about 1,001 terabyte hard drives. They are in the neighborhood of $30 per terabyte these days - so such a storage device would cost about $50,000.

unusual error: '. . . 99 9 ought . . .' the space between the nines is presented apparently by the BBS software running the sight; I tried to edit out the space and found it does not appear in the text I submitted.

'. . . possible per pair of synapses . . .' should read ' . . . possible per pair of neurons . . . ' in post of 8/30/2016 above.

new Hypothetical benefit shows brief pace and survival summary
 

Of course, the numbers shown in this thread's August 30 post are much higher than the number of neurons with involvement in the motor system, estimated as 100,000,000 - controlling about 640 muscles; here is a name list:

List of all the muscles - Functions of the Human Body Systems

Of these, the diaphragm counts as two.

further on the SiTran DiPALS study . . . :
 

One might say there were four groups in the study, with the best candidate group _excluded_ from the study before randomization - theoretically leaving about three groups. We can hypothesize about these remainders by contemplating where the remaining candidates, the ones who opted out before randomization but qualified for the study, fit into the three groups . . . they might have been the best of the candidates . . . or the worst of the candidates. If we add to these candidates the three - one who could not be implanted due some technical difficulty, one who opted out at six months and one who opted out at one year . . . collectively these patients constituted about one-half of a group. They could have been of the best candidate group or of the worst candidate group . . . or distributed among the entire group.

They may have been the BEST of the REMAINING candidates:
As such, could they have opted out because they felt the study was not for the best candidates because the top twenty-five percent (75%-85% FVC range) where disqualified from the study?

They may have been the WORST of the REMAINING candidates:
As such, they would likely have drawn the averages down . . . but by how much?

The report says the FVC average was just above 65% and implies there were no slow regressor/long term survivors in the implanted group but those selected seemed to produce a near-normal distribution of those who qualified.

There were 759 candidates to the study but at the study's closure there may not have been sufficient candidates remaining to fill the final openings as the disqualification rate was much higher than 50%, whereas the FDA HUD/HDE gave an expectation at least 50% would qualify.

. . . more soon . . .

Coma man wakes after 19 years
 

Could one synapse be all it takes:

Terry Wallis, Mountain View, Arkansas:

Coma man wakes after 19 years
Coma man wakes after 19 years | Daily Mail Online

Rom Houben, Belgium:

'I screamed, but there was nothing to hear': Man trapped in 23-year 'coma' reveals horror of being unable to tell doctors he was conscious
Rom Houben: Patient trapped in a 23-year 'coma' was conscious all along | Daily Mail Online

Time's Top Ten Coma Cases:
Complete List - Top 1 Comas - TIME

quick note . . . :
 

I thought I should mention the status of my review of the data I have found on the internet provided by patients who have shared their experiences regarding their use of the pacer. I have found about 180 such patients, only three are believed to have been in the DiPALS study. Based on data supplied by these various patients, the case for the pacer is STRONGER today than at any previous time. Plausibly, the MEDIUM for well timed administration of the pacer may bring patient survival to beyond six years - quite an improvement over the previous achievements. In Bulbar onset though, the MEDIUM might only barely exceed three years. New cases would need to be discovered and such cases would have to be weak cases in order to draw-down the MEDIUM projection appearing to be reasonable interpretations of the current date.

As near as I can tell, the DiPALS group did not report change they detected in the FVS subsequent to implant, whether improved diaphragm movement developed, whether diaphragm thickness improvement developed or whether patients reported any improvement in their sleep.

Its possible none for the DiPALS group met many of the implanted patients because the study was multi-center . . . its theoretically possible no doctor met more than a dozen ALS patients and thus it is reasonable to believe they would not go out on a limb in this case. Therefore, with such limited patient interaction, the Doctors are unlikely to form a strong opinion on the practice - they would need to much larger to occasion - they would want to see many clearly favorable cases].

In short, there is

I just realized the previous post was poorly written, I will re-write and re-post it.

In the electronic edition of the DiPALS report it should be noted they may not have reached their goal of 108 patients even with 759 candidates. After excluding the best 25% of the candidates and relying on the FDA's estimate of about 70% of cases likely to have an eligibility window, a yield of about 400 cases ought to have resulted, yet they were well short of this yield and had less than 100 cases remaining after seventy-four candidates were found.

reposted "amended" quick note
 

I thought I should mention the status of my review of the data I have found on the internet provided by patients who have shared their experiences regarding their use of the pacer. I have found about 180 such patients, only three are believed to have been in the DiPALS study. Based on data supplied by the patients, the case for the pacer is STRONGER today than at any previous time. Plausibly, the _MEDIAN_ for well timed implantation of the pacer may bring patient survival to beyond six years - quite an improvement over the previous achievements. In Bulbar onset though, the _MEDIAN_ might only reach about three years.

As near as I can tell, the DiPALS group did not report change they detected in the FVC subsequent to implant, whether improved diaphragm movement developed, whether diaphragm thickness improvement developed or whether patients reported any improvement in their sleep - as the Onders group reported.

Its possible none of the DiPALS group's doctors met many of the implanted patients because the study was 'multi-center' . . . its theoretically possible no doctor met more than a dozen ALS patients who were implanted and thus it is reasonable to believe they would not go out on a limb in this case - most wouldn't based on such little evidence. Therefore, with few patient interactions, doctors are unlikely to form a strong opinion - they would need larger number of cases - they would want to see many clearly favorable ones.

Further, organizations newly implanting patients are likely to find a larger proportion of cases arriving late in the operating room because patients are more likely to make a timely arrival when the surgery was available in their locality at the time the opportunity window began to open. Such is apparently evident in the series of papers published by the Orders group reflecting steady improvement in apparent efficacy in the later cases.

I should also point out DiPALS challenged the FDA HUD/HDE designation but not the lead research team (Onders, et alia). The HUD/HDE did not contain an efficacy claim. Onders, et alia, have reported evidence of efficacy seen in reduction of FVC slope, thickening of diaphragm muscles, improved movement thereof and improved sleep. What are the credentials of the reporters who commented on the DiPALS report? Do they have an in-industry reputation?

So the statistics suggesting we should expect 300 to 600 fALS diagnoses per year. Vitamin E was discovered to be associated with a decrease incidence of ALS in a study of the American Cancer Society's Cancer Prevention Study II; the study involved nearly one million patients, but further studies found after ALS onset, vitamin E was ineffective. This 2005 report reflects the observations:

Vitamin E intake and risk of amyotrophic lateral sclerosis.
Vitamin E intake and risk of amyotrophic lateral sclerosis. - PubMed - NCBI

Eleven years have passed, we are 3,000 to 7,000 fALS diagnoses later - has a study conducted to test the observation on fALS candidates (who are about 50% likely to develop an ALS diagnosis) to determine whether such patients achieved temporal shift of their ALS symptoms by way of ensuring their pre-symptomatic use of vitamin E favorably shifted their ALS diagnosis or maintained the disease(s) dormancy?

If one were to remove the most successful candidates of the NIV group (to achieve balanced groups because five of the DPS group were not implanted and two of the DPS group left, one at six months and the other at one year) the DPS plus NIV group would clearly prevail . . . although with weaker than expected statistics . . . see figure 2, were they would be about tied at eighteen months and ahead at twenty four months.