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The science of craniocervical instability and other spinal issues and their possible connection with ME/CFS - discussion thread

Discussion in 'ME/CFS research news' started by ME/CFS Skeptic, May 23, 2019.

  1. ME/CFS Skeptic

    ME/CFS Skeptic Senior Member (Voting Rights)

    Concerns about craniocervical instability surgery in ME/CFS

    CCI/AAI has little in common with ME/CFS

    Three ME/CFS patients, Jeff, Jennifer, and Matt, have reported improvements of their ME/CFS symptoms following surgical interventions for craniocervical instability (CCI) and atlantoaxial instability (AAI).

    CCI refers to increased mobility and instability of the craniocervical junction, the transition between the spine and the skull. It normally develops as a result of physical trauma such as a car accident, an inflammation disease such as rheumatoid arthritis or a congenital disorder such as Down syndrome. [1] The main symptoms of CCI consist of severe neck pain, [2] and neurological abnormalities [3] that are quite different from the characteristic ME/CFS symptoms. Young et al. for example describe a case of CCI with chronic neck pain, headache, left-sided facial pain, and numbness. Another case example had progressive worsening of neck pain and frequent falls, which were attributed to balance issues. [4] The case report by Botelho et al. describes a man with insensibility to pain in the left hemithorax and paresis of the hands. [5] Kukrejo et al. report on 49 cases that underwent fusion surgery. The most common presenting symptoms were gait instability, motor weakness, numbness, neck pain and dysphagia (difficulties swallowing). [6] More severe forms of cervical cord compression and trauma to the spinal cord or the brainstem do not result in ME/CFS symptoms but in respiratory distress, pain, cranial nerve dysfunction, paresis and paralysis and in rare cases, sudden death. [7]

    AAI refers to excessive movement at the junction between the superior vertebra of the spine. It also gives a symptom complex that is clearly distinct from ME/CFS. Clinical manifestations of AAI include neck pain, paresthesia, weakness and signs of myelopathy on examination. Other symptoms include difficulties with gait, neurogenic bladder and a lack of coordination. [8]

    The EDS connection

    The link between ME/CFS symptoms and CCI/AAI comes from research on patients with hereditary disorders of connective tissue such as Ehlers Danlos Syndromes (EDS). Following the publication of an influential paper on Chiari malformation and cranial settling in EDS patients in 2007 [9], there was an increase of surgeons diagnosing and treating CCI/AAI in patients with EDS.

    It is worth highlighting that this research is still in its infant stages. There are very little scientific publications on CCI/AAI in EDS. According to a 2016 review by Fraser Henderson, an expert, and forerunner in the field, “there is a paucity of neurological literature referencing CCI in this group of disorders”. Opponents of these procedures argue that “radiological diagnosis of pathological instability at the cranio-cervical junction has not been clearly established in the literature for the hypermobility population.” [10]

    The Henderson study

    This year, Henderson and colleagues published a 5-year follow-up of 20 EDS patients treated with craniocervical stabilization surgery. [11] These were however not the average EDS-patients. They were required to have Chiari malformation, a clear indication of craniocervical instability, to suffer severe headache and/or neck pain and to have “demonstrable neurological deficits”. In addition, patients had to have a diagnosis of what is called “cervical medullary syndrome” a constellation of symptoms and signs that are thought to be caused by compression of the brain stem. According to a 2014 consensus statement [12], the clinical findings of cervical medullary syndrome are:

    i) Headaches, suboccipital pain and neck pain,

    ii) Bulbar and related symptoms: altered vision, diplopia, nystagmus, decreased hearing, tinnitus, imbalance, vertigo, dizziness, choking, dysarthria, dysphagia dysautonomia, postural orthostatic tachycardia, pre-syncopal or syncopal episodes disordered sleep architecture, sleep apnea,

    iii) Symptoms of myelopathy: weakness, clumsiness, spasticity, altered sensation, paresthesias, dysesthesia, change in gait, constipation, urinary urgency and frequency.​

    This is once again a symptom complex that is quite different from ME/CFS.

    Although there were complications in some cases, the fusion surgery performed by Henderson et al. generally led to clinical improvement. Consequently, this study has been used as an example of why surgery for CCI/AAI might also work in patients with ME/CFS. The symptoms which improved most however such as vertigo, headaches, imbalance, dysarthria dizziness or frequent daytime urination were far from the characteristic symptoms of ME/CFS while fatigue, muscle pain, and IBS did not show a statistically significant improvement. The reported improvements in the trial were also not spectacular, given that this was a study without a control group. Patients improved from an average score of 53 on the Karnofsky scale to approximately 70. After 5 years there was only a small increase in work resumption: 60% of patients were still unable to work or go to school.[13] Interestingly, the reasons given by the participants for the lack of improvement in work or school status were other medical problems related to EDS such as musculoskeletal pain, fatigue, gastrointestinal issues, POTS, etc. So instead of given us an indication that CCI/IAA surgery might improve EDS-symptoms that resemble those of ME/CFS, this trial showed the exact opposite. Not only is there a lack of scientific evidence for the efficacy of CCI/IAA surgery in patients with ME/CFS, there is also no indication why this surgery would relieve ME/CFS symptoms.

    Complications: occipitocervical fusion is no joke

    While the benefits of CCI/IAA surgery for treating ME/CFS symptoms are unclear, the risks are obvious. This type of surgery, called occipitocervical fusion, is no joke. It reduces the range of motion of patients’ neck by approximately 30%. [11] The operation takes several hours as pedicle screws are inserted in the body to correct and stabilize the position of the cervical spine. Mattie reported that the surgeons put him on anesthesia for 14 hours and that the first days after the surgery were terrible, being in pain and unable to move or sleep. [14] Recovery is slow and estimated to last several months.

    Although the outcome is generally good, the complications of occipitocervical fusion can be serious and should be taken into consideration. [1,15] According to Choi et al. common complications include screw failure, wound infection, dural tear and cerebrospinal fluid leakage. [16]. In a large review of occipitocervical fusion by Winegar et al. 2010, “surgical adverse events data were recorded for 195 (24%) of 799 cases.”[7] Although the outcomes were generally good in the trial on atlantoaxial fixation by Goel et al., one patient died because of a vertebral artery injury incurred during the operation. [17] In the study by Henderson discussed above, two subjects had superficial infections, of which one returned to the operating room for closure of the rib wound dehiscence. Mild to moderate pain at the rib harvest site was common at 2 years, although substantially abating at 5 years. The study reported that "one to four years after the craniocervical fusion, some subjects developed pain over the suboccipital instrumentation (the "screw saddles") due to tissue thinning, and requested hardware removal (8/20 subjects)."

    Jeff experienced a severe infection following his occipitocervical fusion. On the Phoenix Rising forum he reported:

    “Day 21 post-surgery, the swelling rapidly increased, and my incision site became bright red, inflamed, and the redness was spreading. I spiked a fever of 101.6 and went to the E.R. They admitted me for a week, got me on IV antiobiotics with a PICC line.”[18]​

    Jeff needed another surgery to reopen and clean the incision site. Later he would need another revision surgery to replace 3 screws after a physical therapist twisted his neck too far. [19] Jennifer also experienced complications though it is unclear how these relate to the craniocervical fusion. She needed two extra surgeries in the lumbar spine to remove a hematoma that was compressing her spinal cord (a complication from a prior blood patch). [20]

    It costs a lot of money

    Another concern is the high cost. According to Jeff, Jennifer and Mattie there are only a few neurosurgeons in the world that can reliably perform these treatments. On the Phoenix Rising forum, Matt explained that it costs around 1800 euro’s to get an upright MRI-scan [21], that a consultation with one of these surgeons takes 250-300 euro’s [22] and that the actual fusion surgery costs approximately 70.000 euro’s in Spain and probably more in the United States. [23] Online fundraisers of patients trying to raise 100.000 euro for CCI/IAA surgery in the hope of recovering from ME/CFS, already exist. [24]

    Are these surgeons reliable?

    There is a third concern about these surgeries. If only a few neurosurgeons in the world are believed to perform the craniocervical/atlantoaxial fusion surgery in patients with ME/CFS reliably, one might ask what makes them so unique. Do they have unique skill and expertise, or are they more aggressive in pushing the limits of surgery? Most have private practices, meaning they likely experience a financial incentive to perform more surgeries.

    In 2016, multiple media outlets reported that three patients had filled malpractice lawsuits against Paulo Bolognese, the neurosurgeon that performed Jeff’s fusion surgery. The three women claimed Dr. Bolognese either “gave them unnecessary surgeries or botched their treatment to the point they ended up in worse shape than when they first visited him.” According to mersonlaw, Dr. Bolognese had already been suspended by North Shore in 2010 “for allegedly failing to show up on time for a patient who was anesthetized for surgery — and has been sued at least 20 times over his medical care.” [25] I do not have the necessary information to judge these litigations. I do think it’s important that patients are correctly informed about the fact that some former clients think this neurosurgeon has performed unnecessary and inadequate surgeries on them.

    A noticeable disclaimer

    Given the information provided above, I would advise Jeff, Jennifer and Matt to add a noticeable disclaimer to the interesting and courageous blog posts they write about their past surgeries and current recovery process. The disclaimer should inform readers that:

    (1) The clinical picture of CCI is quite different from ME/CFS.

    (2) There is no scientific evidence to suggest that CCI/AAI surgery relieves ME/CFS symptoms.

    (3) CCI/AAI surgery costs tens of thousands of euro’s and has severe complications including screw failure, wound infection, dural tear and cerebrospinal fluid leakage.

    EDIT 1: In the text, I sometimes used the incorrect abbreviation 'ICC' instead of the correct abbreviation for craniocervical instability: CCI. This has now been corrected. Thanks to @BruceInOz for noticing this.

    EDIT 2: One quote of the Henderson study was incomplete. In a previous version of this text the words (the "screw saddles") were left out of the following sentence: "one to four years after the craniocervical fusion, some subjects developed pain over the suboccipital instrumentation (the "screw saddles") due to tissue thinning, and requested hardware removal (8/20 subjects)" This has now been corrected.

    EDIT 3: Mattie has pointed out that thus far, 3 months after his surgery, he has gone from severe to moderate ME and that this doesn't classify as spectacular. The first sentence: "Three ME/CFS patients, Jeff, Jennifer, and Matt, have reported spectacular improvements..." was therefore corrected to remove the word spectacular.

    EDIT 4: I've added the following section "Although the outcome is generally good" to the sentence: "the complications of occipitocervical fusion can be serious and should be taken into consideration."

    EDIT 5: The sentence "Patients with CCI/AAI suffer from symptoms that are clearly distinct from the symptoms of ME/CFS." has been changed into "The clinical picture of CCI is quite different from ME/CFS” as some readers found the original version confusing.
    Last edited by a moderator: Aug 1, 2019
    Annie, J.G, Colleen Steckel and 63 others like this.
  2. ME/CFS Skeptic

    ME/CFS Skeptic Senior Member (Voting Rights)


    [1] Ashafai NS, Visocchi M, Wąsik N. Occipitocervical Fusion: An Updated Review. Acta Neurochir Suppl. 2019;125:247-252.

    [2] Bobinski L, Levivier M, Duff JM. Occipitoaxial spinal interarticular stabilization with vertebral artery preservation for atlantal lateral mass failure. J Neurosurg Spine. 2015 Feb;22(2):134-8.

    [3] O'Brien MF, Casey AT, Crockard A, Pringle J, Stevens JM. Histology of the craniocervical junction in chronic rheumatoid arthritis: a clinicopathologic analysis of 33 operative cases. Spine (Phila Pa 1976). 2002 Oct 15;27(20):2245-54.

    [4] Young RM, Sherman JH, Wind JJ, Litvack Z, O'Brien J. Treatment of craniocervical instability using a posterior-only approach: report of 3 cases. J Neurosurg Spine. 2014 Aug;21(2):239-48.

    [5] Botelho RV, Neto EB, Patriota GC, Daniel JW, Dumont PA, Rotta JM. Basilar invagination: craniocervical instability treated with cervical traction and occipitocervical fixation. Case report. J Neurosurg Spine. 2007 Oct;7(4):444-9.

    [6] Kukreja S, Ambekar S, Sin AH, Nanda A. Occipitocervical Fusion Surgery: Review of Operative Techniques and Results. J Neurol Surg B Skull Base. 2015 Sep;76(5):331-9.

    [7] Winegar CD, Lawrence JP, Friel BC, Fernandez C, Hong J, Maltenfort M, et al. A systematic review of occipital cervical fusion: techniques and outcomes. J Neurosurg Spine. 2010 Jul;13(1):5-16.

    [8] Lacy J, Gillis CC. Atlantoaxial Instability. StatPearls. 2019. Available at: https://www.ncbi.nlm.nih.gov/books/NBK519563/

    [9] Milhorat TH, Bolognese PA, Nishikawa M, McDonnell NB, Francomano CA. Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and chiari malformation type I in patients with hereditary disorders of connective tissue. J Neurosurg Spine. 2007 Dec;7(6):601-9.

    [10] Henderson FC (2016) Cranio-cervical Instability in Patients with Hypermobility Connective Disorders. J Spine 5: 299. doi:10.4172/2165-7939.1000299

    [11] Henderson FC Sr, Francomano CA, Koby M, Tuchman K, Adcock J, Patel S. Cervical medullary syndrome secondary to craniocervical instability and ventral brainstem compression in hereditary hypermobility connective tissue disorders: 5-year follow-up after craniocervical reduction, fusion, and stabilization. Neurosurg Rev. 2019 Jan 9.

    [12] Consensus statement 2nd international SF dynamics symposium, June 24 & 25, 2013. Manhasset, NY, USA. Available at: https://csfinfo.org/files/1613/9665/4797/Final_Booklet_complete.pdf

    [13] Video (minute 24.30) "Five-Year Follow Up of Craniocervical Fusions" - Fraser C. Henderson, MD.


    [14] https://forums.phoenixrising.me/threads/cci-aai-fusion-surgery-scheduled.75221/page-2#post-2184898

    [15] Garrido BJ, Sasso RC. Occipitocervical fusion. Orthop Clin North Am. 2012 Jan;43(1):1-9, vii.

    [16] Choi SH, Lee SG, Park CW, Kim WK, Yoo CJ, Son S. Surgical outcomes and complications after occipito-cervical fusion using the screw-rod system in craniocervical instability. J Korean Neurosurg Soc. 2013 Apr;53(4):223-7.

    [17] Goel A. Is atlantoaxial instability the cause of Chiari malformation? Outcome analysis of 65 patients treated by atlantoaxial fixation. J Neurosurg Spine. 2015 Feb;22(2):116-27.

    [18] https://forums.phoenixrising.me/thr...-a-cause-of-your-cfs.56908/page-4#post-960342

    [19] https://forums.phoenixrising.me/thr...-cause-of-your-cfs.56908/page-52#post-2186102


    [21] https://forums.phoenixrising.me/thr...-cause-of-your-cfs.56908/page-25#post-1018414

    [22] https://forums.phoenixrising.me/thr...-cause-of-your-cfs.56908/page-36#post-1025294

    [23] https://forums.phoenixrising.me/thr...-cause-of-your-cfs.56908/page-36#post-1025317

    [24] https://www.gofundme.com/go-fund-meine-schwester.

    [25] https://mersonlaw.com/media-outlets-cover-merson-law-malpratice-lawsuits/
    Annie, LadyBirb, Naomi10 and 26 others like this.
  3. ME/CFS Skeptic

    ME/CFS Skeptic Senior Member (Voting Rights)

    I would immediately like to add some caveats to the information I posted above:

    A) I am obviously no expert in these complex surgical procedures and it's possible that there are some inaccuracies in the text above. I simply did some research and read some studies. I hope the information I collected will be helpful for patients to interpret the recent ME/CFS recovery stories. I'm concerned about ME/CFS patients who are too ill to read much and desperate to try anything to relieve their suffering. I hope the skeptical view provided above will help them put things into perspective.

    B) My blog post is not intended to question the CCI/AAI diagnosis of Jeff, Jennifer or Matt. The symptoms they experienced do resemble those associated with CCI/AAI I've read in the literature and I have no reason to doubt their diagnosis.

    C) I've argued that there currently is no scientific evidence to suggest or think that CCI/AAI surgery relieves ME/CFS symptoms. That doesn't mean that it doesn't. Scientific understanding always has to start somewhere. I hope the stories of Jeff, Jennifer or Matt will indeed lead to a greater understanding of ME/CFS and related conditions.

    D) I hope that Jeff, Jennifer and Matt will add the disclaimer to their recovery stories. That said, I realize the complex and difficult situation they are in given their abrupt change in health and the many people reading along or asking questions. I admire their courage to speak openly about this and their willingness to help others. I hope that they realize my text was intended to help others as well.
    Annie, Skycloud, zzz and 40 others like this.
  4. Denise

    Denise Senior Member (Voting Rights)

    @Michiel Tack - I don't know much about Jeff's or Matt's stories so I don't know how they characterized their current state but Jen said clearly that she is in remission. (I view remission and recovery as very different.) Would you be willing to edit your post to reflect that?
    hellytheelephant and DokaGirl like this.
  5. Andy

    Andy Committee Member

    Hampshire, UK
    Confusingly, she says this in one of several emails I've received from being on Unrest and MEAction mailing lists. (Her bolding)
    She uses the term remission in the rest of the email, so perhaps she meant to do that in this sentence, but given that it is purposefully in bold text it suggests, to me, not.
    MEMarge, Naomi10, Maggie and 12 others like this.
  6. ME/CFS Skeptic

    ME/CFS Skeptic Senior Member (Voting Rights)

    Hi @Denise. Just to be clear: I didn't write that they claimed to have recovered from ME/CFS. I used the terms "recovery story" or "recovery process" to describe what they wrote in blog pots and on social media. I don't think this is inaccurate. Jenn wrote: "I believe I am on my way to a full recovery." while Jeff wrote "Just like me, Jen Brea has fully recovered from ME after her fusion surgery for CCI/AAI."
  7. Hip

    Hip Senior Member (Voting Rights)

    It's good to enumerate risks, costs and uncertainties involved in such surgery as you have done.

    A couple of points though:
    That's true, the range of motion is usually substantially reduced. But Jeff said here:

    I am not sure if we can say that at this point.

    Jeff said that out of 20 or so ME/CFS patients who were tested for CCI/AAI by MRIs sent to these CCI/AAI expert surgeons, over 90% tested positive, at least in the judgement of those surgeons. Just how many of those 20 were also positive on the neck traction test (a positive result is if symptoms reduce under traction), I am not sure. I am not sure how many have taken the traction test.

    We would have to go through the symptoms of all these 20 patients to see if they had any unusual additional symptoms (as Jeff and Jen did, with the transient inability to breathe when their head was in certain positions, I am thinking possibly due to breathing muscle nerve pinching), or whether their symptoms were just standard ME/CFS.

    Some of these 20 patients are detailed in these two threads:

    20 patients now found positive for CCI / AAI, there must be many more...
    Tracking CCI / AAI MRI & Treatment outcomes
  8. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

    London, UK
    I think you are right to call these recovery stories both for the reasons you give and because in both everyday and medical usage we use these terms in all sorts of slightly different ways in different contexts. In the context 'recovery story' recovery need not imply permanent and complete cessation of an underlying disease.
  9. roller*

    roller* Senior Member (Voting Rights)

    would patients with such a background like jen (with thyroid disease) and jeff (with eds/virus ?) have ever been permitted to a MECFS stanford study (or ron davies) or fluge/mella ... ?`
    Dechi and DokaGirl like this.
  10. Denise

    Denise Senior Member (Voting Rights)


    Thanks for clarifying.
    I guess I have a problem with the term recovery - in large part because many patients with ME have better and worse periods and some even have significant improvement for a while (days-years).
    Others have mentioned the concerns about Bell's 25 yr follow-up and how patients say they are recovered but when further questions are asked their activity levels aren't those of a well person.
    Recovery to me would be like a broken bone that has healed, a tumor that has been excised with clear margins....
    Maggie, JaneL, Simone and 4 others like this.
  11. Trish

    Trish Moderator Staff Member

  12. Milo

    Milo Senior Member (Voting Rights)

    Actually, recovery is not the right term to use for your example of cancer. It only takes one cell to escape, and circulate in the blood stream to form a metastasis. Oncologists are instead using the ‘5 years disease free’ measure to take this into account. After 5 years, the chance of cancer coming back is significantly lower.
    KathyD, Ellie_Finesse, JaneL and 6 others like this.
  13. Denise

    Denise Senior Member (Voting Rights)

    Thanks for making me aware. I appreciate it.
    JaneL, DokaGirl and Trish like this.
  14. Grigor

    Grigor Senior Member (Voting Rights)

    Very grateful for the information you provided!!
  15. JES

    JES Senior Member (Voting Rights)

    Actually one of the first patients that Fluge/Mella studied had cancer and ME/CFS, which is why she received rituximab. This patient had an unexpected remission in her ME/CFS following rituximab treatment for her cancer, which started the whole hypothesis that rituximab would work for ME/CFS. So I don't see why Jen's thyroid cancer is in an way related to her ME/CFS diagnosis. And high viral titers like in Jeff's case are reported by hundreds of ME/CFS patients, they don't mean there is an active viral infection so he isn't disqualified from having an ME/CFS diagnosis because of that.
  16. Stewart

    Stewart Senior Member (Voting Rights)

    Thanks for taking the time to put this together and share it @Michiel Tack. I don't agree with your statement that cervical meduallary syndrome is "a symptom complex that is quite different from ME/CFS" - from what I've read there seems to be a substantial overlap between the two definitions - but not withstanding that, this is a clearly set-out and cogently argued set of comments and observations.
    MSEsperanza, JaneL, Simone and 3 others like this.
  17. Binkie4

    Binkie4 Senior Member (Voting Rights)

    Just thinking and there may be an obvious answer that escapes me.

    Presumably the 3 surgeons who are reported to be most competent at this surgery-Gilete, Henderson and a third- have considerable experience at operating on patients with this condition, maybe hundreds of patients each.( Do we know how many they have each operated on?) That is how they became experts.

    But so far as we know only 4 patients with ME have been operated on, Jeff, Jen, Mattie and a fourth who is still recovering in hospital. So if their other patients did not have ME, what is the difference between the ME subgroup and the rest? Why did the rest not develop ME?

    I’m thinking of David Systrom, pulmonologist at Brigham, whose specialty was exercise intolerance. He found that a large proportion of his patients had ME which has led him into researching ME.

    Are the neurosurgeons doing 0-2 spinal fusions finding that large numbers of these patients have ME? If not, why not?

    Am I missing something obvious?
  18. Sean

    Sean Senior Member (Voting Rights)

    I thought that cancer recovery/cure was defined as the time point after treatment when the risk to that individual of that specific cancer returning fell to the baseline population risk for anybody getting that cancer.
  19. DokaGirl

    DokaGirl Senior Member (Voting Rights)

    Thank you very much @Michiel Tack for your very detailed info. Quite eye-opening.

    I am NOT trying to convince anyone that CCI and AAI are the same as ME.

    Although I am enthused about these 3 people's recoveries, and the very tentative link to Chiari malformation, and brain stem issues, noted in the CCC, it's a BIG step from ME to this diagnosis and treatment.

    Much, much further research is needed.

    In the past I researched and cautiously underwent treatment based on another pwME's positive reviews, and ended up being permanently harmed.

    Treatment outcomes may vary.

    I think there are some overlap in symptoms between CCI/AAI and ME, but several differences.

    There is overlap with ME and other diseases, e.g. hypothyroidism re extreme fatigue, as I experienced it before my hypothyroid diagnosis some 40 years ago.

    I have learned that the body can only react so many ways.

    Misdiagnoses, as we've seen are numerous.

    I am including the link to the CCC Overview here re the discussion of symptoms - pages 2 to 9 (page 9 under "X-ray &/or MRI of Brains and Spinal Cord" advises to look for minor stenosis among a list of other things:


    A few symptoms of note missing from the list for CCI and AAI but involved in ME are PEM, flu-like feelings, swollen and/or painful lymph glands, and low grade fevers.

    Thank you very much again for all your work on this!
  20. wingate

    wingate Established Member (Voting Rights)

    Thank you for the summary, @Michiel Tack. I think you make a lot of great points.

    Although @Hip notes, via Jeff's observations, the high rate of positive finding for "CCI/AAI" among pwME evaluated, I don't think much can be taken from these results. What is the validity and reliability of the test? What would the findings be among healthy controls? Are the people who have been tested representative of the pwME population?

    I also do not understand how traction would be a good test of symptom relief. Isn't the patient immobile during the procedure? And are they upright or lying down? Wouldn't some sort of exercise or exertion be required or at least helpful to determine whether symptoms were resolved? Can anyone say more about this?

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