The Honourable Deb Matthews
Ministry of Health and Long-Term Care
Government of Ontario
80 Grovener Street, 10th Floor
Tel: (416) 327-4300
Fax: (416) 326-1571
Email: email@example.com I am writing to you about a severe lapse in care for the large population of Ontarians suffering from Myalgic Encephalomyelitis and ask that you take steps to ensure the health and proper care of these individuals.
People with ME/CFS represent a very vulnerable population with unique needs when it comes to institutionalized care such as hospitalization, rehab, respite and Long Term Care. For Canadian healthcare to be truly universal, it must include appropriate services for it's entire population - including patients with ME/CFS.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is a neuro-immune illness that affects cognitive and physical functioning. It was found to affect 1.4% of Canadians in a 2010 CCHS study, including almost 400,000 people in Ontario. Twenty-five percent of the diagnosed are estimated to be severely affected, being bed-ridden with little to no functioning. This population has been shown in studies to have the lowest functioning of any chronic illness, comparable to end-stage AIDS or end-stage renal failure. There is no known cause or cure, though autopsy findings report dorsal root ganglionitis - a type of inflammation of the spinal cord - confirming it's status as a neuro-immune illness. Some people improve with time while others are bed-bound for decades. It is estimated that 4% of those with severe ME/CFS have any type of recovery.
To die of this illness is atypical; however, to hover in an in-between state where one experiences a 'living death' for years or decades is not.
Despite the ravages of this illness, it is one of the least funded in terms of research dollars, receiving slightly more funding per year in the US than Hayfever.
In memory of Emily Collingridge who died March 18, 2012 I ask that a dedicated care unit for people with ME/CFS be created in a Toronto Hospital so this group has a safe, healing place to go when they need Long Term Care, hospitalization or respite for themselves or their caregivers. Emily was not the only person with ME/CFS to die or relapse from standard hospital care, but I really want her to be the last.
I have been hospitalized and/or been in LTC care facilities in Ontario for over two years in my thirties. I had to leave the hospital via ambulance without being discharged to avoid imminent death. Hospital and LTC experiences almost killed me and led to severe relapses that I have yet to recover from.
In 2005, I was paralyzed, unable to speak, mostly unable to open my eyes and spent my day concentrating on getting liquified food poured into my mouth by my mother. I was admitted to Scarborough General Hospital in 2005 on the recommendation of my ME/CFS specialist, Dr Bested. I did quite well there, as I was in the ‘Acute Care for the Elderly/Neurology’ unit - a pretty low-key place with lots of care. Folks averaging 90 years of age recovering from strokes were my main companions, along with RNs and RPNs. Amazingly, no PSWs were allowed to work on the unit. (PSWs are health care aides that can get their designation with a 6-week course and an IQ of about 85, and they are taking over a lot of the hands-on patient care in Ontario hospitals.) Eventually, I relearned to walk at SGH, and my rehab was progressing very slowly, but steadily. Then, government guidelines dictated that I be moved to a Rehab Hospital, as I could not stay any longer at an acute-care facility. Unknown to me at the time, this transfer was to be my undoing, erasing all the gains I had made at the acute care facility. I had a very difficult time getting accepted to rehab because there were days on record where I was too ill to participate in physical therapy (even though I was making improvements), which was not acceptable for someone deemed as a psychiatric patient with no medical illness, thanks to a crackerjack psychiatrist who ‘diagnosed’ me a few months out of medical school. The previous 5 diagnoses of ‘Post Viral Fatigue Syndrome’ and/or ‘Myalgic Encephalomyelitis/Chronic Fatigue Syndrome’ (all under the rubric of WHOs ICD-10 G93.3) somehow fell by the wayside, largely because my neurologist Dr Gardner-Maher stated that ‘people with that can walk’, which of course, is not necessarily true.
Finally, I was accepted to transfer to Bridgepoint Health. My preconceived ideas of what Rehab Hospital was all about caused me to feel like I’d just won the Lotto Super7. When I got there, I had my first major relapse within 2 weeks due to overexertion in Physical Therapy. My doctor (the Chief of Staff) maintained that ME/CFS probably didn’t exist as an illness as he’d never seen a case (note: as of 2006, it is illegal to hold this opinion in Ontario as a doctor). I relapsed severely a few months later from hospital chemical exposure from the cleansers they used August 1, 2005 for spring cleaning. To show the house-cleaning ethos at Bridgepoint, I introduce Joe, the cleaner on the unit who’d come to work at 7AM singing opera at the top of his lungs. He used to spray about 50-100 squirts of ‘pink stuff’ onto everything in the room to clean it. One day, a woman was there to clean instead of Joe; I noticed that she sprayed 3 squirts of ‘pink stuff’ into a large bucket-full of water and used that to clean the entire room. I asked why she did it like that and told her about Joe’s method. She got very nervous about this information and promptly left. So, I’m not too surprised that 5 kids super-cleaning my room with God-knows-what left me paralyzed, unable to feed myself, brush my teeth, wash my face or speak. I rallied a bit for a few months, unable to walk my usual 24 meters per day, but able to stand at times, transfer and be taken for showers on the commode. But, for all intents and purposes I’ve never walked since. Dr Malkin maintained that I didn’t walk because I ‘didn’t want to’ and the patient care manager told me I’d have to force myself to do my own feeding and tooth-brushing because the ‘PSWs were not intelligent enough to understand why [I] needed help with those tasks’. They had her whipped was the real truth. So, even though I was paying for my stay at this point, my mother had to come in every lunch and dinner to feed me and do my personal care. Finally when the manager was on vacation, my friends went to her replacement to discuss the issue; she put her foot down, making the PSWs give me the care I needed from that point forward.
Then, I got the privilege of being the youngest person ever, at age 34, to be transferred to the 6th floor: the purgatory for people awaiting nursing home placement. One woman was screaming ‘mama!’ 24/7, patients would wander into my room to either take my things, ask me to marry them or try to force feed me cheese. Staff on 6E dubbed the unit the ‘Zoo’. It was routine for PSWs to treat these elderly patients as non-entities: they would come into our room at night to party, talk on cell phones and sometimes even physically or mentally abuse those residents who would be unable to report them. I became chronically sleep deprived. One day, I recognized PSW Cavell from the night shift (her gossiping had kept me awake until 7 AM). I asked her why she didn’t let us sleep at night. Her reply, “Life’s a killer, baby. Oh you’re so pretty, it’s so sad. Nobody cares about these people [sweeping hand gesture], they’re all just going to nursing homes.” So, from this honest, narcissistic sociopath I had my answer. I complained to management, who told me she’d talk to the head night nurse Suzanne, which didn’t do a lick of good as Suzanna was one of the worst offenders. I continued to deteriorate and by November 2006, I felt I was dissolving into the ether. I left the hospital in an ambulance without being discharged to save my life. I have still not recovered from the relapse this hospitalization caused even though it’s been 6 years. I relapsed again upon my short LTC stay in 2008, experiencing transient paralysis and losing my ability to talk for several months. Even though I had clearly stated my needs to them, they did the opposite of what I had asked, thinking they could ‘cure’ me.
Hospital and LTC experiences have almost killed me and led to severe relapses that I have yet to recover from: becoming paralyzed again, unable to sit up, walk, or stand are the very severe consequences I suffered from my time in the institutions of Ontario’s Health Care System. At this point, I would likely choose the possibility of death instead of going through the tortures of hospitalization again, and that shows there is something very wrong with the current system.
This is indeed the situation that Lynn Gilderdale found herself in prior to her death at age 32 in 2005. She was bedridden and routinely hospitalized every winter for the infections she always caught. Before her last winter approached, she realized that she could not tolerate another hospital admission. Knowing that her infections were fatal without treatment, she nevertheless decided that she had to stay at home. She died of a morphine overdose prior to having to deal with the next bout of winter infection.
There are many hospital horror stories in regards to ME/CFS patients. Thirty-year-old Emily Collingridge was another ME/CFS patient who told me she relapsed severely after a previous hospital visit. I recently discovered that Emily died this past Sunday, March 18, 2012 in hospital. For me this was a call to action: too many ME/CFS patients die or relapse from not having appropriate hospital care that accommodates their very unique needs. Too many refuse hospitalization for this reason, and end up dying or relapsing at home because they can’t tolerate getting the care they need in a hospital setting. Conversely, others go to hospital and end up dying or relapsing from the care they receive. I believe the four previous publicized ME/CFS deaths in UK were due to starvation, malnutrition and/or dehydration as these patients were unable to chew or swallow. Lois Owens died weighing a mere 50-60 lbs because she could not take in nutrition, and apparently avoided hospital admittance for reasons known only to her family. Sophia Mirza died at age 32; she also could not take in nourishment and refused to go into hospital again because of her previous experiences which led her to relapse and never recover. Her death certificate was the first in the UK to state ME as a cause of death; the indirect cause was acute renal failure due to dehydration. A hospital visit done right could have given these young women the option of the nourishment they needed through inserting a gastric or naso-gastric tube.
People with ME/CFS often cannot tolerate sensory stimuli including touch, sound, smell and visual input as it gives them neurological overload. The need a very quiet, low-lit place just to keep whatever functioning they have. They need to avoid the regular hospital cleaning agents as patients usually also have Environmental Sensitivities and can lose functioning if a nurse haphazardly sprays some seemingly innocuous thing like Febreeze or Lysol. The genetics of their methylation is different and they simply cannot manage in a toxic environment without relapse. They suffer from insomnia and have a greater need for sleep than any other illness population; if they don't sleep, global functioning decreases and severe relapse can follow. People with severe ME/CFS are also in such a weakened state, which compounded with extreme sensory over-load, produces a situation where they often can't bear to have visitors even sit with them. Consequently, having social and health care workers with anxiety, post-traumatic stress disorder or flighty behaviours service their needs is not appropriate. ME/CFS patients who are bedridden may only have a limited amount of times their body can be moved before relapsing; the can't be serviced by someone who rolls them over, puts on a diaper, rolls them back, then realizes they forgot to put the soaker under neath, consequently needing to roll them back agin, etc. They need workers who possess a strong skill-set and who are grounded, responsible and experienced to provide their services so they don't relapse. They need doctors to believe they have an organic illness.
To relate the unique difficulty that people with severe ME/CFS have, I point to the case of Emily Collingridge. Even when she was in horrendous pain and needed morphine, often she would have to choose to forgo it's administration by her mother when she was too sensitive to tolerate having her mum enter the room. Even this seemingly passive act could sometimes cause intolerable neurological overload to the point of having to refuse medication that was desperately needed, and Emily would have to remain with pain so severe it caused her to hallucinate.
I have had similar instances in hospital where a PSW asked if I was in pain. I was indeed, but I shook my head 'no' because I knew if I indicated 'yes' the nurse doused in perfume would come in talking about American Idol (and why wasn't I interested?), asking questions about the pain and insist on taking vitals which was way more commotion than my brain could tolerate without further relapse. I wasn’t able to talk anyways, but she didn’t ‘get’ that and would keep asking the questions louder and more forcibly as if I were deaf instead of having sensory-input issues coupled with the most severe weakness you could imagine.
People with ME/CFS are extremely sensitive and must be cared for with these sensitivities in mind or they will relapse. Cleansers that they can tolerate must be used for room-cleaning, like industrial strength colloidal silver that is used at the Hospital for Sick Children. Staff in the unit where ME/CFS patients reside must use scent-free products, as is the practice in all public establishments in Halifax, Nova Scotia. The unit needs to be quiet: no pianos, televisions, radios, clowns jingling bells, strangers bursting in to play the violin, etc., as some patients are so sound-sensitive, they cannot tolerate even the sound of others breathing. Visitors must be quiet and their numbers must be limited (upon my admission to the Scarborough Hospital, General Division there were nineteen people in my 4-bed ward, even though there was a generous 2-visitor per person policy with a very visible notice up). The lights must be totally out at 9PM so that proper sleep is ensured; lights in the hallway must be dimmed by 80% if the patient chooses to have their door open at night. Efforts must be made to accommodate those who have a reversed sleep-schedule. Staff cannot yell and act boisterously on the floor, or play tricks on patients for their own amusement. Air purification units must be present for their ‘white noise’ and there ability to keep air clean; Aller-Air Air Medic is a great choice and is made in Montreal. The diet must be able to accommodate the many and varied sensitivities of people with ME/CFS, and as a default should start with being gluten-free, dairy-free, excitotoxin-free and free of artificial colours and preservatives. Some people with ME/CFS cannot tolerate being spoken to without relapsing; others cannot read or speak; this does not mean they are ‘out of it’ and automatically give up the right to direct their own care; it means they need specially-trained RNs or RPNs to administer it. They really need private rooms, and to have the option of signing a waiver to have the door closed at night and to refuse hourly night-time checks and vitals measurements so that they can sleep. Ideally, PSWs would not be allowed to work on the unit, and specially trained RPNs and RNs should administer care.
Myself, I have been taken off the CCAC’s LTC care list for one of the homes I applied for - the Arthur Meighan Manor - as they said they could not care for my needs once I stated them. I have not informed the other LTC home of my needs in fear that they would do the same. LTC facilities for those with ME/CFS need to be much more than just ‘live body storage’ as is unfortunately often the case. They also do not have enough staff to cater to someone with ME/CFS, who may need bed-baths done right because they can’t endure the shower (even in a trolly), or because it may take them several hours to get some watered down liquid chicken into their system. I have no home. I have applied for Assisted Living, though am not well enough to live on my own with attendant care (again, I will not tell CILT that, and hope I eventually improve), and am unsure as to when they can provide me a unit anyways. As you can see, I have fallen through the cracks to a place where I am worse off from Ontario’s Health Care services, faced with the very real problem of where to house my body so that it can actually heal; my elderly mother can’t do it indefinitely.
I hope I have adequately argued the need for a small dedicated care unit in a Toronto hospital for ME/CFS patients needing hospitalization (for whatever reason), rehab, LTC and respite. An eight-patient unit staffed by one nurse, with access to PT/OT services in one Toronto hospital would be a great start, and would not cost that much. By consolidating the patient group into one area instead of having it scattered throughout the GTA, and by creating a healthy environment, we will have better patient outcomes which means saving provincial monies in the long term.
I am willing to collaborate with your team to the best of my abilities to create such a unit in Toronto to make Healthcare in Ontario inclusive of this very vulnerable patient population.
Please respond to the above letter in general, and to the following three issues, specifically, in writing:
- when you will undertake the vital initiative to provided a dedicated care unit for people with ME/CFS in need of hospitalization, LTC, rehab and respite
- when you will mandate a scent-free/chemical-free policy to be adopted by all health care institutions in Ontario
Thank you for making Canada’s healthcare universal by being inclusive of the nearly 400,000 Ontarians living with ME/CFS.
- what are people with ME/CFS supposed to do in the meantime if they need LTC or hospitalization to get their care needs met if hospitals and LTC centres are refusing to meet these needs?
In Emily's memory, I petition the Health Minister of Canada to provide a unit dedicated to the care of those with ME/CFS that need hospitalization, respite and LTC in Toronto, Canada's largest city. Please join me by copying and pasting this letter (or parts thereof) and sending it to the addressee below, as well as to politicians in your own area of residency to help create healthy institutional care for people with ME/CFS.PLEASE CLICK HERE TO SIGN March 22, 2012
The Honourable Leona Aglukkaq, P.C., M.P.
Brooke Claxton Building, Tunney's Pasture
Postal Locator: 0906C
Ottawa, Ontario K1A 0K9
Dear Honorable Aglukkaq, PC, MP, Minister of Health - Canada
I am writing to you about a severe lapse in care for the large population of Ontarians suffering from Myalgic Encephalomyelitis and ask that you take steps to ensure the health and proper care of these individuals.
This letter is prompted by the recent death of 30-year old Emily Collingridge who died in hospital in the UK with severe ME. Ms Collingridge severely relapsed due to her previous hospital admission and never recovered. General hospital practices led to her death and to the deaths of Lois Owens, 27; Lynn Gilderdale, 32; Sophia Mirza, 32, and countless others with this illness, either directly or indirectly. It is time that at least one hospital in Toronto have a unit for the dedicated care of ME/CFS patients and their special needs so that this does not happen here.
Here is a quote from Indigo Jo blogger Matthew Smith to give an idea about the unique issues people with ME/CFS face regarding hospitalisation:
Emily suffered a severe relapse after the book was published, prompted by an unavoidable hospital admission, and correspondence from her family has said that she had endured very extreme pain and other symptoms since, although they decline to go into some of the details. However, one depressing aspect of her recent experience is that she has refused to be readmitted to hospital because, on previous occasions, “the hospital weren’t able/willing to meet her need for a quiet and dark care environment which had a devastating impact on her body”.
Severe ME (and sometimes, less severe ME) often heightens the senses of the sufferer, so that any touch can be experienced as pain and much (or sometimes any) noise and light can also be very painful. Emily Collingridge noted that, during a previous admission during a previous crisis, she could hear the doctor whispering to her parents that her heart might give up, and he did not believe she could hear them. Hospital wards, as anyone who has ever visited an inpatient in one, let alone had to be in one, will know, are not particularly restful places, even at night, something I remember from visiting my sister in one a few years ago; she had not been able to sleep properly because of the constant noise and activity on the ward at night. What this must be like for a patient who really needs quiet and other stimulation reduced or eliminated does not bear thinking about.
It really begs the question of why London, [or Toronto, Canada] a wealthy city of some 7 million people, cannot provide a facility like this: a suite in a hospital where staff are trained to deal with patients with sensitivities to noise, light and chemicals; such patients include ME sufferers but also those with Multiple Chemical Sensitivities (MCS) and, perhaps, autism (obviously, in conjunction with whatever else they are in for), and where they receive minimal disturbance, an environment suitable for their sensory needs, and where they are not exposed to harsh-smelling chemicals such as certain cleaning agents. Needless to say, they need to be staffed by people who understand (and accept) these conditions and are sensitive to the patients’ needs. I’ve never had experience of running charity appeals, but there needs to be an appeal to raise funds for such a unit so that patients like Emily can feel safe in an institution which is there to heal their sickness (or ease its symptoms and complications, if they can’t deal with the illness itself) rather than make their suffering even worse.
I have been hospitalized and/or been in LTC care facilities in Ontario for over two years in my thirties. I had to leave the hospital via ambulance without being discharged to avoid imminent death. Hospital and LTC experiences almost killed me and led to severe relapses that I have yet to recover from: becoming paralyzed again, unable to sit up, walk, or stand are the very severe consequences I suffered from my time in the institutions of Ontario’s Health Care System. At this point, I would choose the possibility of death instead of going through the tortures of hospitalization again, and that shows there is something very wrong with the current system.This is indeed the situation that Lynn Gilderdale found herself in prior to her death at age 32 in 2005. She was bedridden and routinely hospitalized every winter for the infections she always caught. Before her last winter approached, she realized that she could not tolerate another hospital admission. Knowing that her infections were fatal without treatment, she nevertheless decided that she had to stay at home. She died of a morphine overdose prior to having to deal with the next bout of winter infection.
People with ME/CFS are extremely sensitive and must be cared for with these sensitivities in mind or they will relapse. Cleansers that they can tolerate must be used for room-cleaning, like industrial strength colloidal silver that is used at the Hospital for Sick Children. Staff in the unit where ME/CFS patients reside must use scent-free products, as is the practice in all public establishments in the entire province of Nova Scotia. The unit needs to be quiet: no pianos, televisions, radios, clowns jingling bells, strangers bursting in to play the violin, etc., as some patients are so sound-sensitive, they cannot tolerate even the sound of others breathing. Visitors must be quiet and their numbers must be limited (upon my admission to the Scarborough Hospital, General Division there were nineteen people in my 4-bed ward, even though there was a generous 2-visitor per person policy with a very visible notice up). The lights must be totally out at 9PM so that proper sleep is ensured; lights in the hallway must be dimmed by 80% if the patient chooses to have their door open at night. Staff cannot yell and act boisterously on the floor, or play tricks on patients for their own amusement. Air purification units must be present for their ‘white noise’ and there ability to keep air clean; Aller-Air Air Medic is a great choice and is made in Montreal. The diet must be able to accommodate the many and varied sensitivities of people with ME/CFS, and as a default should start with being gluten-free, dairy-free, excitotoxin-free and free of artificial colours and preservatives. Some people with ME/CFS cannot tolerate being spoken to without relapsing; others cannot read or speak; this does not mean they are ‘out of it’ and automatically give up the right to direct their own care; it means they need specially-trained RNs or RPNs to administer it. They really need private rooms, and to have the option of signing a waiver to have the door closed at night and refuse hourly night-time checks and vitals measurements so that they can sleep. Ideally, PSWs would not be allowed to work on the unit, and specially trained RPNs and RNs should administer care.
Myself, I have been taken off the CCAC’s LTC care list for one of the homes I applied for - the Arthur Meighan Manor - as they said they could not care for my needs once I stated them. I have not informed the other LTC home of my needs in fear that they would do the same. LTC facilities for those with ME/CFS need to be much more than just ‘live body storage’ as is unfortunately the case. I have no home. I have applied for Assisted Living, though am not well enough to live on my own with attendant care (again, I will not tell CILT that, and hope I eventually improve), and am unsure as to when they can provide me a unit anyways. As you can see, I have fallen through the cracks to a place where I am worse off from Ontario’s Health Care services, faced with the very real problem of where to house my body so that it can actually heal; my elderly mother can’t do it indefinitely. I hope I have adequately argued the need for a small hospital unit/long-term respite centre for this extremely vulnerable population. Even an eight-patient unit staffed by one nurse in one Toronto hospital would be a great start, and would not cost that much; actually it would save provincial monies in the long run as healthier people are more productive people.
I am willing to collaborate with your team to the best of my abilities to create such a unit in Toronto. The Women’s College Hospital may be one option to house such a unit, as they already have an Environmental Clinic with many of my suggestions already implemented.
Please let me know in writing when you will undertake this vital initiative. Also, please let me know what myself and others in this situation are to do in the meantime, a) to ensure that the places that are supposed to help us don’t end up harming us, and b) to ensure we have a place to live.
Very sad news for the ME community: Emily Rose Collingridge died on March 18, 2012 after a lengthy hospital stay at the age of 30. No other details have been released. Emily was a strong advocate and wanted her experience to help ease that of others with severe ME, leading her to author the book Severe ME/CFS: A Guide to Living
. I include an excerpt from our last correspondence via her connection to the outside world - her Blackberry- to show in her own words what a shining star she truly was, and a bit of what she's had to endure during her illness. May Emily be at peace, and may all the awareness she has worked so hard to create continue to grow. My deepest sympathies to her family."Like you I'm sure, I am so pleased to think that my experience of severe ME will lead to others having a somewhat better time - and that's why I choose to make as much effort as is humanly possible in relation to awareness raising and the provision of information (though often it's very far from good for my physical health, it is good for my mental health - apart from when the frustration of campaigns etc not achieving change leads me to feel despondent over the situation for people with ME despite knowing that small progress does occur and, though we want and deserve much more, I realise that any improvements are nonetheless important and a crucial step towards achieving real positive change) . I know the fact that others also have done so before, or in addition to me, has definitely been of great benefit for me.
Your experiences have been incredibly similar to mine! As you probably know, I also improved to the point of being able to walk a little in the house with a walker before relapsing as a consequence of a hospital stay. Not only has my ME at its worst, as with you, made it seem to me and those around me that I must be dying, complications of my illness have actually brought me very close to death in reality - I could so easily not be alive today and I would die now if it were not for the very powerful cocktail of drugs I'm prescribed and take daily via my tummy - I have a feeding tube through my abdomen, injection and syringe driver, the way in which we protect me from sensory, physic and intellectual stimulation and the IV infusions have from time to time in hospital. As I think I said in my appeal ME is truly a hideous, ugly, monstrous disease."
Here is an obituary for Emily Collingridge written by activist Matthew Smith that provides some back-story into Emily's experience of ME/CFS and some valuable links to her work:
Ottawa 2011 Conference Reports Pt V: the Brain Studies
by CORT on MARCH 16, 2012via Phoenix Rising
IACFS/ME Ottawa 2011 Conference Reports
Many researchers think the problems in the brain or central nervous system probably play a key role in ME/CFS. Some of the most interesting research in the past couple of years has focused on the brain and the Ottawa conference was no exception.
At the conference we saw research findings begin to focus on specific areas of the brain, a spinal fluid study suggesting a brain injury is leaking proteins into the spinal fluid, a nasal study demonstrating more whacky autonomic nervous system results and a paper suggest that for some patients, it may all be in the nose……
The Seat of Fatigue in the Brain Identified?
Andrew Miller, Jones, Drake, Tian, Unger. Decreased basal ganglia activation in CFS subjects is associated with fatigue
The basal ganglia and related areas in the brain were news for a while. Several studies in the early 2000s appeared to be pointing an arrow straight at these areas, but, as happens so often in CFS, positive study results don’t necessarily mean more funding…and the studies stopped; but Andrew Miller, the Director of the Mind/Body Program at Emory University, in association with several CDC researchers has revived interest in this area.
The study - In this study, the CFS patients showed reduced activity of two parts of the basal ganglia, the caudate and the globus pallidis. The fact that basal ganglia activity and fatigue levels were correlated in the ME/CFS patients but were not in the healthy controls highly suggested that the basal ganglia plays a role in producing fatigue in ME/CFS (as it appears to do in Parkinson’s disease, MS and other disorders.)
The basal ganglia in the deep brain may be the seat of fatigue production in ME/CFS and other disorders
Focus on the Basal Ganglia – Sitting in the interior of the brain, the basal ganglia consists of six interconnected nuclei (including the amygdala) that provide a link with the limbic system and the hypothalamus.
A Deep Brain Focus – Several factors suggest that deep brain organs like the basal ganglia could play a role in CFS. These organs seem to excel in affecting both emotions and physical activity, both of which (at least in my case) have taken a hit in this disorder. The basal ganglia are hit hard in a number of highly fatiguing disorders (Parkinson’s disease, MS, stroke and AIDS). Dopamine activity in the basal ganglia plays an important role in mood, motivation, sleep/wake (arousal), cognition and motor activity. Study evidence suggests problems with dopamine metabolism may play an important role in ‘central pain/fatigue’ states such as Fibromyalgia.
Poor Planning? – Does just the thought of doing something overwhelm you sometimes? Basal ganglia problems could be a reason for that. Almost ten years ago two CFS researchers, Chaudhuri and Behan, proposed that the reduced self-motivation and increased fatigue seen in all central fatigue disorders (CFS, Parkinson’s, MS, etc.) is at least partly due to poor functioning in the basal ganglia; specifically its inability to effectively process the cues needed to do tasks. (This hearkens back to studies suggesting that problems with ‘motor planning,’ i.e. the planning needed to engage in movement, may make movement more effortful in ME/CFS. Apparently the brain conceptualizes movement before it occurs. …Both models touch on the idea that the ME/CFS brain has particular difficulty in ‘planning,’ which does have some intuitive appeal…)
Several small magnetic resonance spectroscopy (MRS) studies have found increased choline peaks in the basal ganglia of CFS patients, possibly due to membrane damage, perhaps due to infection (See Choline on the Brain?).
Miller proposed several reasons why the basal ganglia seem to be less effective in people with ME/CFS.
Increased pro-inflammatory cytokine activity. Pro-inflammatory cytokines have long been associated with fatigue. The cytokine/fatigue association was blown open when it was found that the administration of interferon alpha – a cytokine used to combat hepatitis – produced profound fatigue and flu-like states in many patients. Researchers later discovered that IFN-a also produces reduced glucose uptake (e.g. reduced activity) in yes, the basal ganglia.
Infection (and the ‘Good’ Fatigue) – Fatigue is believed to be an adaptive response initiated by the brain to slow the body down, assisting healing and inhibiting the spread of the pathogen. In a discussion during a break Miller related that he felt viruses played a key role in ME/CFS. He talked about a system that was on alert – and for a good reason. Miller sees ME/CFS from an evolutionary or ecological perspective. When, he asks, might having fatigue be better than having a high energy level? When the body needs to conserve its resources in order to heal itself, and having co-workers and friends visit would spread a pathogen to them.
Infection Whacks Basal Ganglia Functioning – During the Q&A session, Dr. Miller noted that toxins associated with some bacteria (endotoxins) also have been shown to reduce basal ganglia functioning. These toxins apparently promote inflammation and pro-inflammatory cytokine production, and thereby produce fatigue and altered moods.
Interestingly, in some individuals these cytokines can cause ‘increased arousal’ – perhaps a more common state in ME/CFS than depression. (Dr. Baraniuk thinks the research community has been way off base with its focus on depression in ME/CFS….the much more common state, he believes, is ‘increased arousal’ caused by too much sensory information flooding the brain.)
Gene Silencing – Dr. Miller wasn’t sure, though, that whatever started the problem is still there, and he talked about an alternative culprit to pathogens. He said that when the body is attacked by a virus, or in the midst of some other traumatic event, the immune system revs up to fight off a possible attack. During the revving up process, things can go wrong, and he thinks a level of controls called ‘epigenetics’ may have gone awry in people with CFS. Studies have shown that immune activation can trigger the methylation process to turn genes on or off – permanently – causing what is called ‘epigenetic changes’.
(If you feel really different after coming down with CFS – if this theory is right – then it’s possible that you really are, genetically, somewhat different; that is, the genes you are born with are not acting in the same way.) In the case of CFS, he suggested that a methylation process triggered during infection could have altered the functioning of a main immune regulator, the glucocorticoid system.
He’s not the first to suggest this. Just last year, CDC researcher Falkenburg found evidence of increased methylation of a serotonin transporter in CFS (Neuromolecular Medicine, 2011 (13) 66-76) At the Ottawa conference, Falkenburg unsuccessfully looked for evidence that methylation had turned down the activity of genes that produce perforin in natural killer cells. Both Falkenburg and Miller are looking for physiological changes triggered by that initial infection (or whatever it was) which altered the playing field for people with ME/CFS.
Epigenetic processes result in size differences in genetically identical mice
Pressing the Reset Button - Some work is going into reversing these harmful epigenetic changes. Miller stated anti-methylation drugs have changed cowering lab rodents with epigenetic changes into exuberant, active ones and he related the story of a chemotherapy patient with documented epigenetic changes whose depression scores went way down when given an anti-methylation drug. He said it was like pressing a ‘reset button’. (‘Chemofog’ and similar CFS symptoms are common outcomes of cancer treatment.) Could people with CFS be displaying epigenetic changes caused by immune activation? Only time will tell.
Immune Modulation - Given his focus on the immune system, it wasn’t surprising that Dr. Miller is intrigued by the use of immune modulating drugs, not just to combat overt infection, but to affect ‘neuropsychiatric’ symptoms such as pain, fatigue and sleep. He noted that ‘cytokine antagonists’ (e.g. Enbrel, etc.) are helping to explain the contributions cytokines make to depression and pain (and fatigue). With some physicians now using them successfully to reduce pain in cancer patients, the role of immunomodulators and immune suppressants appears to be opening up. (A recent Miller paper argued for the use of more immune drugs to suppress pain in cancer.)
Direct immune modulation is becoming more and more an option for the right kind of CFS patients. Immune modulation can have serious consequences, but a pattern seems to building. Ampligen, of course, is an immunomodulator, and rituximab, a B-cell depressant, had excellent (if transitory) results in some patients. Dr. Klimas and other ME/CFS specialists appear to be exploring these powerful drugs for selected patients.
Dr. Miller had many intriguing ideas, but unfortunately his time with the CDC and CFS is over and he’s moving on.
The Mysterious CDC Insula Study
Interaction of Self- and Illness-related Cognitive Processing in the Right Anterior Insula of the CFS patients: an fMRI study. Jones, Rajendra, Drake, Miller, Unger, Tian, Pagnoni
“Something is happening here
But (we) don’t know what it is
Do (we), Mister Jones?”
Bob Dylan “Ballad of a Thin Man”
Andrew Miller, an accomplished psychoneuroimmunologist who presented his own fMRI brain study, stated that he didn’t have a clue what this study was about.
Dr. Jones is surely close to ending his long stint on the CDC’s CFS research team and they have been giving him room to roam. Dr. Jones’ first interoception paper in 2005 paper laid out his idea that abnormal behavior in several regions of the brain (insula, anterior/posterior cingulate, orbitofrontal cortex) might be associated with autonomic nervous system problems and increased symptoms.
He theorized that, depending on which part of the brain is affected, people with ME/CFS might respond well to pharmacological drugs, biofeedback, meditation or CBT. (Before his departure, Dr. Reeves stated a study was underway at the CDC that would match therapies to brain scan results; i.e. pharmacological drugs would be used to treat one type of brain dysfunction, meditation, another, etc.)
The insula is a hot topic in the neuro-endocrine-immune disorder field. Insula problems have been found in a number of ‘central sensitization’ disorders such as FM, IBS, TMJ and now the insula is showing up in ME/CFS.
Focus on the Insula
Could over-activation of the insula cause problems with stimuli and pain in CFS?
The insula is a fascinating organ in the brain that in some ways seems almost made to order for ‘central sensitization’ disorders. Got problems with bright lights, sharp noises or painful body sensations? It’s the insula that determines how bright the lights are or how painful your body sensations are. Got concentration problems? One recent paper suggests that the high levels of insula activity found in FM may actually impair their working memory as the insula ‘steals’ resources from other parts of the brain. (Several studies indicate that inability of CFS brains to turn off their attention to things like background noise is an energy drain as well. )
Exercise and Emotions – Interestingly, the insula is activated by two factors problematic for CFS patients – exercise and negative emotional experiences – and it regulates two systems at the core of ME/CFS symptoms – the autonomic nervous and immune systems. The insula helps control blood pressure and blood flows during and after exercise, affects gastric motility (IBS symptoms?) and even speech and coordination – all of which tend to falter after exercise in CFS.
(Might one ME/CFS study (Bogaerts et al. 2007), that showed a propensity for reduced CO2 levels when ME/CFS patients imagined negative experiences, also point to the insula as the cause? It suggested poor autonomic nervous system functioning (blood flows, blood pressure) in response to a negative emotional hit.)
In his study, Jones asked people with CFS a series of questions related to illness and ‘self’. The CFS patients had the same level of insula activity to questions asked about illness which were not related to the self, but an increased insula response to questions about illness related to themselves. The healthy controls did not exhibit increased activation in response to these questions.
Jones concluded that one of two things could explain the increased insula activity in people with CFS: physiological problems that underlie their symptoms, or aberrant interoceptive processes that cause fatigue and other symptoms to be experiences more strongly than usual.
We’ll learn more about the first Jones interoception study when the full paper comes out, but the conclusions – ME/CFS is caused either by physiological aberrations or by problems with interoception – didn’t on the face of it appear to add much to the field.
Assessment of regional cerebral blood flow in CFS using arterial spin labeling MRI; Dyke, Weiduschat, Mao, Pillemer, Murrough, Natelson, Mathew, Shungu
Are anterior cingulate problems in ME/CFS causing problems with heart rate, blood flows, pain and decision making?
Dr. Shungu, the lead researcher in this study, has published two studies finding increased lactate levels in the brains of ME/CFS patients. A byproduct of anaerobic energy production, the increased levels of lactate in the brain suggested that some sort of reduced oxygen usage in the brain might be present, caused by reduced blood flows, mitochondrial dysfunction, high rates of oxidative stress, or all of the above.
In this study, he took a long look at the most prominent theory: that reduced blood flows in the brain are causing high rates of oxidative stress, which punch out the mitochondria causing high levels of lactate. The low blood flow theory works in so many ways; we know that blood volume is low in ME/CFS; plus, there is evidence of blood pooling in the lower parts of the body, which would reduce blood flows in the brain; plus, postural tachycardia syndrome (POTS) is synonymous with reduced blood flows to the brain. It sounds like it’s gotta be happening.
Unfortunately, Dr. Shungu, using a new technique, didn’t find evidence of substantially reduced blood flows in the brain! Lower blood flows were found in CFS patients but they were only 4% smaller, and instead of being broadly spread across the brain, they were quite localized. Shungu expected a bigger decrease and a greater area of the brain with low blood flows.
Read more about Dr. Shungu’s study with Dr. Natelson and his finding of decreased glutathione levels in the brains of ME/CFS patients in Kim McCleary’s interview – http://www.research1st.com/2011/10/07/brainiacs/
Focus on the Anterior Cingulate (ACC) - The place low blood flows were found, the anterior cingulate, however, was interesting. This is not the first time this part of the brain has popped up in ME/CFS research; it, like the basal ganglia, seems almost made to order for this disorder in some important ways.
Forming a kind of “collar” in the back lower part of the brain, the ACC regulates autonomic nervous system activity (heart rate, blood flows, etc.), pain sensitivity, ‘premotor’ (movement) control and what are called ‘rational cognitive functions’ such as decision making and reward anticipation. (For my part, difficulty making decisions should rank as one of the top cognitive problems in ME/CFS. It’s just pitiful sometimes… Of course, the movement problems for a formerly athletic person are also bizarre.)
Connections, Connections – Divided into two parts, a cognitive (rear – dorsal) and an emotional (front – ventral), the ACC is strongly connected with several areas of interest in ME/CFS such as the insula and the amygdala; the ACC has shown up in studies before. Schmaling (2003) found a marked ACC activation both in fatigued multiple sclerosis and in CFS patients. The ACC’s involvement in motor learning/planning and ‘attentional tasks’ suggests, as do the basal ganglia findings, that the planning process for movement may be impaired in ME/CFS. Interestingly, hepatitis treatment with interferon alpha also results in ACC activation. (A recent Miller paper suggested that the same processes occurring in IFN-a induced fatigue may be occurring in ME/CFS. Tying the fatigue processes in hepatitis C treatment and ME/CFS together would be a huge boost for the legitimization of ME/CFS.)
(Personal aside – long term planning has not been my strong suit after CFS. During a transfer factor treatment that temporarily boosted me out of my CFS-like state, however, I began thinking about and making plans for the future. It was like a circuit got reconnected….Once the bloom faded, I was back in my day to day grind. On a gut level, my guess is that all sorts of planning processes in the brain have taken a hit.)
Another study (Yamamoto, 2004) found reduced numbers of serotonin transporters in the front part of the ACC in CFS. A ‘feel good’ neurotransmitter that contributes to feelings of wellness and health, reduced levels of serotonin transmitters in the ACC could play a role in the pain and basically crappy feelings found in CFS. Falkenburg at the CDC recently found evidence of reduced transcription of serotonin in people with CFS.
CDC - Using brain scans, including magnetic resonance imaging (MRI) and positron emission tomography (PET), Emory scientists have found that IFN-alpha affects two parts of the brain, the basal ganglia and the dorsal anterior cingulate cortex (dACC). The basal ganglia play an important role in the regulation of motor activity and motivation as well as symptoms of fatigue. Indeed, IFN-alpha effects on the basal ganglia were linked with symptoms of fatigue. Ongoing studies at CDC are currently evaluating whether similar changes in the basal ganglia occur in patients with CFS. The dACC is a brain region associated with arousal and alarm, and changes in this brain region have been found in connection to anxiety.
Baraniuk Proteome Studies Suggest Brain Injury
Spinal fluid study suggests a brain injury may be present in ME/CFS
Dr. Baranuik of Georgetown University had to unexpectedly leave the conference early but he was clearly happy about the results of his second proteome study. He presented more abstracts than any other individual and expects many papers to result.
Spinal fluid proteome analyses are pretty hot right now…The Schuster/Natelson study differentiating CFS patients from Lyme disease and healthy controls definitely got Dr. Natelson excited – something you don’t see very often. Baraniuk presented posters, not talks at the Conference – so our information is pretty scanty but things should get interesting soon…..
Distinct Clustering of Cerebropsinal Fluid Peptides and other Ion Peaks in Clusters of CFS and Healthy Subjects. J. Baraniuk, O Adewuyi, C Di Poto et. al.
Distinct Cerebrospinal Fluid Proteomic Patters in Clusters of CFS and Healthy Subjects
One study found evidence of four distinct subsets suggesting that ‘four distinctive pathophysiological mechanisms’ are present in the CFS population. Some of the significance factors (:=p<0.00001) were enormous, suggesting a very wide differentiation indeed. In his first brain proteome paper about five years ago Baraniuk presented evidence of a single proteomic signature in CFS and FM. Now, with his much larger and more complex study using better technology, he’s finding distinct subsets..
In most of these subsets he’s finding ME/CFS patients have higher levels of proteins in their spinal fluid. Where does he think these proteins are coming from? A brain injury that’s releasing proteins into the cerebrospinal fluid.
’Exercise’ Test Reveals System Under Disarray
Blunted Nasal and Systemic Sympathetic Reflexes in Chronic Fatigue Syndrome. J Baraniuk, U. Le, K. Petrie et al.
Dr. Baraniuk, like many other researchers, has been fascinated by the role the autonomic nervous system plays in this disorder. Got a perennial case of sniffles, a clogged up nose or nasal drip? Dr. Baraniuk believes this may be caused by autonomic problems and he finds this kind of non-allergenic rhinitis in about 75% of people with ME/CFS.
In this study he had the participants clamp down hard on a hand grip while sticking what looked like a large horn into their nasal passages to measure nasal volume…..Since clamping down hard on the handgrip should stimulate the sympathetic nervous system to narrow the blood vessels in the nose (reducing nasal volume), increasing heart rate and blood pressure.
He found that all those things happened with the healthy controls but remained flat in the CFS group. One group had immediate increases in SNS measures which then decayed or even negative over time suggesting that their systems quickly pooped out quickly demonstrating in Dr. Baraniuk’s words “dysfunctional ‘on-demand’ sympathetic” activity.
Another Possible (and Treatable) Cause of ‘CFS’
Chronic Rhinosinuitis as an overlooked Chronic Fatigue Exclusionary condition
Chester believes some cases of CFS are due to treatable sinus infections
Dr. Alexander Chester is another Georgetown professor who has noticed sinus problems in people with ME/CFS. In his poster presentation Dr. Chester noted that not only is fatigue common in chronic rhinosinusitis (CRS) but that one study showed that ‘vitality scores’ in CRS patients were lower than in patients with congestive heart failure, chronic obstructive pulmonary disorder or chronic back pain.
Two studies, one which suggested surgery was more effective for severely fatigued (than less fatigued) people with CRS and one which found patients with FM and CRS responded better to surgery than patients with just CRS, suggested this approach might be effective for some with pain and fatigue producing disorders.
Chronic sinusitis or inflammation of the sinuses usually caused by a chronic viral or bacterial infection and Dr. Chester noted that it usually begins with an upper respiratory infection – much like ME/CFS does. It can cause stuffiness, head pains, headaches, post-nasal drip and fatigue. Cat Scans often do not pick up abnormalities in patients who later improve after surgery and there are no blood tests for it.
Ampligen Study Sparks Hopes for FDA Approval of First Drug for CFS
by CORT on MARCH 18, 2012via Phoenix Rising
Short-take: Hemispherx provides added proof of Ampligens efficacy in ME/CFS and allays safety fears but is it enough?
Hemispherx has published a major study on the effects of Ampligen (Rintatolimod) on CFS. This study constitutes Hemispherx’s response to the problems the FDA cited in its refusal to approve Ampligen for CFS in Dec 2009.
A Big Blow – In what journalist (and Hemispherx critic) Adam Feuerstein called a ‘staggering blow’, in Dec. 2009, the FDA told Hemipherx that it could not approve Ampligen’s use in ME/CFS until the following issues have been settled. Hemispherx needed to:
The FDA asked a lot for a small company when it asked for an expensive 300 person study and Hemipherx stock prices plunged 43% on the news. A strong skeptic, journalist Adam Feuerstein noted that Hemispherx has unsuccessfully attempted to prove the drug works in a ‘dizzying’ array of diseases (hepatitis B and C, smallpox, HIV, ebola, avian flu , swine flu- HINI) and predicted the drug would never be approved. (Shortly after the XMRV Science paper, in an ill-fated move, Hemipherx embarked on studies attempting to prove Ampligen efficacy in treating XMRV infected patients.) Feuerstein suggested the company might not be able to financially meet the FDA’s demands but Hemispherx has persevered.
- Show credible evidence of Ampligen’s efficacy using expanded studies that are at least six months long
- Show that Ampligen is safe; ie that it does not cause autoimmune disorders or heart problems (prolonged qt intervals)
- Produce studies in which patients are on more than one dose regimen
- Produce studies in which at least 300 patients are on doses intended for the market
- Follow the FDA’s ‘recommendation’ that rodent studies be done to examine carcinogenicity
- Provide additional on quality control issues
- Fix Inspection issues at one of Ampligen’s facilities
It wasn’t easy…..Hemispherx had to apply for two extensions on its drug application but now in a study featuring some of the most well-known CFS providers (Dr. Peterson, Dr. Bateman, Dr. Lapp) they’ve provided the FDA with their best response to its concerns. This placebo- controlled, double-blinded, crossover study may be a make or break moment for Ampligen.
Tough Test – Hemispherx had a tough test. The ME/CFS patients taking Ampligen had to become physically stronger; specifically they had to walk significantly longer on a cardiopulmonary exercise test than those who were taking saline solution. (Hemispherx originally used Karnovsky (functional self-assessments) as the end-point for their studies but Karnovsky score increases (50-55), while helpful, were not particularly significant).
Hemispherx looked at past exercise tolerance studies to determine how much improvement the FDA has needed to approve drugs that purport to improve exercise tolerance and found that the magic number was “6.5″. They felt if they could show that people on Ampligen walked 6.5% longer than the people on the saline solution Ampligen should – according to the past history of FDA decisions – have a good chance of getting approved.
A Sick Group – with Karnovsky scores from 40-60 this group was pretty ill. The median Karnovsky score for the group was 50 which translates out to ” requires considerable assistance for daily care”. (Hemispherx called the study members ‘severely debilitated’). Most were middle-aged women (67-77%) (average age 43 years) who had been ill for about 9 years. Given the quality of the doctors participating in the study there was no question about whether they had CFS or not.
This was a big study over 200 people starting the study and with 194 patients completing it.
The Test – the participants were asked to walk until they could walk no more on a treadmill which tilted up and got harder to walk on the longer they walked.
Check Them Off – Ampligen increased exercise tolerance, reduced medication usage, improved most well-being scores and was safe.
- Exercise Tolerance – At the end of 40 weeks, the patients on Ampligen were able to stay on the treadmill about 108 seconds longer while the patients not on Ampligen were able to stay on the treadmill about 27 seconds longer. This translated to an 16.6% increase in exercise tolerance – far surpassing their goal of at least 6.5%. In fact, according to the study, the 16.6% increase makes Ampligen the best exercise intolerance reducer yet tested by the FDA. (The next best result was posted by Tracleer for pulmonary hypertension (10.6%) and then Remodulin (8.0%).)
- Safety Issues -Few serious side effects were seen in this study and with earlier data suggesting that Ampligen may, in fact, have positive effects on the heart, hopefully the FDA’s fears have been allayed.
- Decrease In Other Drug Use – Hemispherx was eager to show that taking Ampligen enabled patients to reduce their use of other drugs. Interestingly, most patients in both the saline and Ampligen arms of the study reduced their medication usage but patients on Ampligen reduced their drug use more than those on the placebo. (Some of the drugs that were reduced when Ampligen was being used may have contributed to the heart issues the FDA was concerned about.)
- Well-being Scores – Ampligen treated patients increased their Karnovsky scores from a median of 50-55 (requires considerable assistance for daily living to requires less assistance for daily living), their vitality score doubled and their activity score went up somewhat (but was ‘significant’). Interestingly their SF-36 scores, a common measure in CFS studies to measure perceptions of general health, did not budge at all.
Conclusion – In this latest study Hemispherx complied with several of the FDA’s requests. It provided proof of efficacy in a larger study and provided more data on safety issues. The FDA, however, rejected Hemispherx’s claims of Ampligens efficacy in two studies that had similar findings. A third study should help but while Hemispherx did fund a larger study (@ 200 people) it wasn’t able to met the FDA’s requests for a 300 person study or to examine the effects of multiple dose ranges or do rodent studies.
Will this be enough for the FDA? Disorders which have no drugs available tend to get a break with them but Ampligen’s road with the FDAhas been a long one and only time will tell.
Is Ampligen the cure for ME/CFS? Not according to this study but it does appear to have passed several FDA criteria for approval. While the results weren’t stunning we know that some people do very well on Ampligen and if the FDA approves this drug determining who it works for will be important and could ultimately help to subset this disorder. Hemispherx believes the work its doing with a biotech firm called Chronix (see below) will allow it to pinpoint individuals who will benefit from the drug.
Other Hemispherx News
In March 2011 Hemispherx announced that it and Chronix had joined forces to produce a diagnostic test for ME/CFS using advanced DNA sequencing techniques. Howard Urnovitz, Chronix CEO suggested a revolution in understanding ME/CFS was in store stating
“”We capture what is happening to the DNA very early in and throughout the disease process, in real time, and patient by patient,” Howard Urnovitz, CEO and CSO of Chronix Biomedical, said in a statement today. “That’s how our approach differs from other tests that focus on static genomic data or protein biomarkers.”
The companies applied for a patent for a blood test for ME/CFS and stated their new technology would also reap dividends in determining which types of CFS patients responded to Ampligen.
Ampligen Study Take II: A Correction
by CORT on MARCH 18, 2012
The recent blog [above] on Hemispherx’s Ampligen study has been amended to take account of the fact that the study involved an analysis of data from a 1998-2004 study. The blog in its original state suggested that this was a new study done in response to the FDA’s 2009 concerns. That was not true. Hemispherx may have done a re-analysis of old data in an attempt to comply with some of the FDA’s concerns but it did not, at least in this paper, embark on a new study with new patients. My apologies for any misconceptions.
Most people who have ME/CFS also have genetic mutations in their genes involved in methylation, namely MTRR, MTR and perhaps MTHFR. For these people, just going by lab diagnostics for B12 is useless at best, and misleading at worst. Their B12 needs are extremely high.
Vol. 128 No. 12, December 1993
Neurologic Degeneration Associated With Nitrous Oxide Anesthesia in Patients With Vitamin B12 Deficiency
Teresa S. Flippo, MD; Walter D. Holder, Jr, MD
Arch Surg. 1993;128(12):1391-1395.
Vitamin B12 [cobalamin] is an integral component of two biochemical reactions in man: the conversion of L-methylmalonylcoenzyme A into succinyl coenzyme A and the formation of methionine by methylation of homocysteine. The transmethylation reactionis essential to DNA synthesis and to the maintenance of the myelin sheath by the methylation of myelin basic protein. Active vitamin B12 contains cobalt in its reduced form (Co+). Nitrous oxide produces irreversible oxidation to the Co++ and Co+++ forms that renders vitamin B12 inactive. Five cases (four from the literature and one new case) are presented in which patients unsuspected of having vitamin B12 deficiency developed subacute combined degeneration of the spinal cord following nitrous oxide anesthesia. Patients with vitamin B12 deficiency are exceedingly sensitive to neurologic deterioration following nitrous oxide anesthesia. If unrecognized, the neurologic deterioration becomes irreversible and may result in death.
(Arch Surg. 1993;128:1391-1395)