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.  The main symptoms of CCI consist of severe neck pain,  and neurological abnormalities  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.  The case report by Botelho et al. describes a man with insensibility to pain in the left hemithorax and paresis of the hands.  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).  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.  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.  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 , 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.”  The Henderson study This year, Henderson and colleagues published a 5-year follow-up of 20 EDS patients treated with craniocervical stabilization surgery.  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 , 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. 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%.  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.  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. . In a large review of occipitocervical fusion by Winegar et al. 2010, “surgical adverse events data were recorded for 195 (24%) of 799 cases.” 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.  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.” 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.  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).  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 , that a consultation with one of these surgeons takes 250-300 euro’s  and that the actual fusion surgery costs approximately 70.000 euro’s in Spain and probably more in the United States.  Online fundraisers of patients trying to raise 100.000 euro for CCI/IAA surgery in the hope of recovering from ME/CFS, already exist.  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.”  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.