This surgery fuses people’s skulls to their spines to treat a condition overlapping with myalgic encephalomyelitis

For people with cranio-cervical instability (CCI), a debilitating condition linked to connective tissue disorders, this surgery can help reduce symptoms.

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When Dr. Kenneth Liu first saw Unrest, Jen Brea’s 2017 award-winning documentary chronicling her experience living with myalgic encephalomyelitis (ME), he emailed her hoping to help: She reminded him of some of his patients. 

Brea explained that Liu, a vascular neurosurgeon who also treats people with the connective tissue disorder Ehlers-Danlos syndrome (EDS), told her he suspected she had instability in the top (cervical) vertebra — a condition known as cranio-cervical instability (CCI). Then, a friend of Brea’s who has ME suggested she visit Paolo Bolognese, the surgical director of Mount Sinai’s Chiari-EDS Program.

ME is frequently triggered by an infection; Brea believes she developed the disease following a 2011 infection with coxsackie B virus. She also developed postural orthostatic tachycardia syndrome (POTS), an autonomic nervous system disorder that involves low blood flow to the head, causing rapid heartbeat, dizziness, and fainting when people change positions. When her head was in a certain position, she’d abruptly gasp for air; eventually, she’d black out when she stood. Her health deteriorated until she was bedbound for weeks on end. 

Bolognese examined Brea, monitoring her heart, lung, and brain function, and determined that her skull appeared to be “sinking on top of the neck,” compressing not only the arteries supplying the brain with oxygenated blood, but also the vertebrae holding up her skull. In turn, this compressed the brainstem — the part of the brain that controls automatic functions like breathing — putting it to sleep. Brea’s breathing slowed until her oxygenation levels were so out of whack that her brain sent emergency signals to wake her with a panicked gasp.

Bolognese, who estimates that ME impacts roughly one in three of his patients, diagnosed Brea with CCI. “I remember feeling such a profound sense of peace, even if I wasn’t able to get the surgery, just knowing after seven years what was causing it,” Brea said.

About six weeks later, Bolognese performed cranio-cervical fusion, a neurosurgical technique that relieves pressure on the brain. In the procedure, two 2.5-centimeter titanium bars and six screws fuse the top two vertebrae to the skull. It “has been done by many neurosurgeons for decades,” said neurologist Dr. Ilene Ruhoy, who works with Bolognese as the medical director of Mount Sinai’s Chiari-EDS clinic. 

The surgery lifted Brea’s head by 4 millimeters and put her POTS in remission. “I felt like I could finally breathe again, like my blood was getting enough oxygen,” she said. She found it “helped with restoring normal function in all of these areas of my body.”

A growing number of doctors agree that a minority of people with ME are like Brea: Some of their symptoms are caused by CCI linked to connective tissue disorders. Viruses including SARS-CoV-2 have been shown to degrade connective tissue, Ruhoy points out, which could be a big issue for people with Long COVID and those getting multiple SARS-CoV-2 infections.

Over the past two decades, Bolognese estimates he’s performed more than 300 cranio-cervical fusions for people with connective tissue disorders from 50 states and 72 countries. Some doctors say that any patient with multiple complex, interconnected conditions causing debilitating symptoms that doctors struggle to explain should be evaluated for CCI — and that for some of those patients with CCI, surgery may be the only solution.

Still, the procedure remains controversial. Over the years, Bolognese has faced over 20 lawsuits from cranio-cervical fusion patients. All those lawsuits have been dropped or settled, and neurosurgery faces a high rate of legal challenges.

The connective tissue connection

Healthy connective tissue is like a sturdy sheath that holds the spinal column together, including the cranio-cervical junction at the base of the skull that enables your head to rotate. Bolognese compares the loose connective tissue in hypermobility patients to overcooked rib meat: so tender it falls off the bone. 

For these people, an infection like SARS-CoV-2 may trigger mast cells — an immune cell found in connective tissue — to gobble up their connective tissue. Both ME and Long COVID are linked to mast cell activation syndrome (MCAS), in which mast cells become too active. This can, in turn, lead to loose connective tissue. For some, this leads joints to move beyond the usual range of motion, known as hypermobility.

In fact, some research suggests at least half of people with ME have hypermobility. That’s roughly twice the rate of the general adult population. In severe hypermobility cases, it’s associated with connective tissue disorders like EDS. 

In some cases of hypermobility, loose ligaments may cause the top vertebrae in the cervical spine to collapse under the weight of the head, leading to CCI, Ruhoy explained. “It’s like having a bowling ball supported by a stick,” said Dr. Peter Rowe, a pediatric ME specialist who studies connective tissue disorders.

CCI can compress the brain and slow the flow of blood and cerebrospinal fluid, which cushions the brain and spinal cord. It may impact the hypothalamus, the control center for the body’s hormonal system, as well as the autonomic nervous system, which governs breathing and heart rate. 

This exacerbates common ME and Long COVID symptoms such as severe dizziness, fatigue, and cognitive dysfunction. One small study found that 80% of people with ME have abnormalities in their cervical spine. Research suggests many people with ME also have POTS.

Roughly half of Long COVID patients may qualify for an ME diagnosis — and Long COVID doctors are already seeing CCI warning signs in their patients. Ruhoy estimates that at least half of her EDS patients have Long COVID. Dr. David Kaufman, who treats people with ME and related conditions, is actively evaluating roughly 10% of his Long COVID patients for CCI. And Dr. Alba Azola, a rehabilitation specialist at the Johns Hopkins COVID clinic, said about 40% of her Long COVID patients have hypermobility. Three have significant CCI symptoms. 

“COVID is like a nuclear bomb” in the way it hits many organs and causes a “profound immunologic inflammatory response,” said Kaufman, an internal medicine doctor who treats Brea at the Center for Complex Diseases. “There’s too much inflammation, and that also injures the connective tissue.” Some studies have noted an increased rate of autoimmune and autoinflammatory connective tissue diseases, such as lupus and rheumatoid arthritis, after a SARS-CoV-2 infection. 

“COVID is like a nuclear bomb” in the way it hits many organs and causes a “profound immunologic inflammatory response.”

Dr. David Kaufman

A “Rosetta Stone” moment

In the early 2000s, doctors misdiagnosed the dizziness, headaches, weakness, and nausea that Marissa Irwin experienced when she was upright as migraine, thyroid imbalance, heart arrhythmia, and low blood pressure. Prescribed treatments didn’t help.

Then a radiologist mentioned something odd on Irwin’s MRI: Her brain slightly bubbled through the bottom of her skull. He told Irwin not to worry: It appeared within a “normal” range. Unconvinced and desperate for answers, Marissa’s mother rolled her into Bolognese’s clinic in a wheelchair. “She was a black hole. You did not see her. She had no light, no life in her eyes,” he said. 

At the time, Bolognese had recently co-founded the Chiari Institute, a neurosurgery clinic in Long Island treating Chiari malformation type 1 — a congenital condition that often causes CCI. In people with Chiari, the cerebellum appears crammed inside the skull like an uncomfortably small shoe, Bolognese said. While many people don’t even know they have Chiari, some experience disabling symptoms.

He didn’t think Irwin had Chiari, in which MRI images of the brain bubbling into the spinal canal are so apparent “that a medical student could recognize the problem from across the room.” Rather, she was experiencing “something more insidious.” 

At the time, a Chiari diagnosis required the cerebellum to exceed the base of the skull by at least five millimeters. Anything less was considered “normal.” Irwin’s herniation was two to three millimeters; Bolognese was surprised her radiologist even mentioned it. The scans also showed Irwin had CCI.

Stumped by how someone without the Chiari malformation could have CCI, Bolognese attempted a maneuver he used on Chiari patients: He grabbed Irwin’s head in his hands and lifted it off her spine. “All of a sudden, the lights went on and she woke up. She became energetic. She started moving her arms and legs,” he said. But when he let her head go, the symptoms returned. 

Bolognese deduced that Irwin’s CCI was due to lax cervical ligaments, the rubber bands that hold the neck joints together. He recommended making the effects of traction permanent with cranio-cervical fusion. Following the surgery, Irwin — who was later diagnosed with ME — “not only rebounded…she started having a normal life,” he said.

For Bolognese, Irwin’s diagnosis was “a Rosetta Stone moment,” after which he began looking actively for CCI in patients with connective tissue disorders as well as those with the congenital mutation.

A complex diagnosis

There is no standard, recognized criteria for determining which hypermobility patients should have surgery for CCI, but Bolognese insists on a “highly selective” diagnostic process to reduce the risk to patients. People with ME also often try nonsurgical options such as a neck brace and physical therapy before considering the surgery.  

Bolognese has developed an evaluation including an extensive questionnaire and invasive cervical traction, a formal version of the procedure performed on Irwin. It simulates the surgery using a machine: Bolognese screws two clamps on the ends of a metal headband into the sides of a patient’s skull. Using a pulley system to progressively add weight on one end, the clamps on the other end raise their head from their shoulders. “Very often these patients start crying because they never felt so good,” Bolognese said.

For people bedbound with ME, the surgical outcome is “almost literally like rising from the dead,” said Kaufman. Yet, little research proves its effectiveness. Rowe conducted a 2023 study involving 53 people with EDS and CCI. He found that three-quarters of the 32 patients who underwent cranio-cervical fusion self-reported significant improvement in debilitating symptoms more than two years after the procedure. Notably, 25% of patients who underwent surgery said their quality of life remained the same or worsened. 

Some people don’t improve as doctors hope. Even when surgery does address CCI, “it can’t possibly fix everything else that the hypermobility imposes,” explained Rowe. Because loose connective tissue remains, over time the joints below the fusion often fail like dominoes, Bolognese said. 

Even when surgery does address CCI, “it can’t possibly fix everything else that the hypermobility imposes.”

Dr. Peter Rowe

Bolognese likens CCI to diabetes, a chronic disease that often has concurrent conditions. For example, patients often return for a myriad of other spinal issues. One is tethered cord syndrome, a nervous system disorder in which tissue attachments reduce spinal cord mobility. It can be addressed with another surgery. 

Brea had tethered cord surgery a couple of weeks after her craniocervical fusion. “I couldn’t stand up straight. I had even more tension on my cord, because my head had been lifted during surgery,” she explained. Brea found that tethered cord surgery helped relieve symptoms she’d downplayed since childhood, including urinary frequency and numbness in her feet.

“With some of these pathologies, tethered cord in particular, people can have them since they’re children. And because you’ve always been inside your own body, you don’t know what ‘normal’ feels like,” she said.

Unfortunately new tissue attachments can form, a phenomenon called retethering, which can recreate the original symptoms. Other patients say that anecdotally, spinal retethering is a lot more common than neurosurgeons admit — and it can be difficult to address. Further tethered cord release surgeries and therapies like extracorporeal shockwave therapy (which uses high-frequency sound waves to promote tissue repair in people with musculoskeletal disorders linked to neurological diagnoses) don’t work for everyone.

There is an alternative surgery, spinal column shortening, which can reduce the strain on the spinal cord from retethering, but it is extremely difficult and can be financially inaccessible. And it doesn’t always solve related issues some patients face.

Continuing controversy

Cranio-cervical fusion on hypermobility patients “still remains controversial in many neurosurgical circles,” Ruhoy said. Kaufman estimates that Bolognese is one of five U.S. surgeons who perform the procedure; two have stopped performing it on EDS patients due to the risk involved. Hypermobility patients have a higher rate of complications due to their lax connective tissues and poor wound healing, among other challenges.

Doctors have voiced concerns about a lack of quality evidence for the surgery’s efficacy and disagree about diagnostic criteria. Bolognese and others are actively performing studies to provide this evidence. Dr. Lucinda Bateman, who treats patients with connective tissue disorders as the founder and medical director of the Bateman Horne Center, worries the surgery’s risk-reward calculation might not add up, especially for people who aren’t bedbound. Many have incremental improvement, and for some, symptoms worsen.

Bolognese acknowledges it’s a challenge. On the one hand, MRI results may look “normal” to non-specialists. On the other hand, people have very complex symptoms. He has found it challenging to present “in a convincing way, this new sub, sub sub sub discipline, to colleagues.” 

Lawsuits against Bolognese — none of which are ongoing — claimed malpractice and fraud for purportedly not taking “proper” preoperative imaging, not diagnosing tethered cord syndrome in a timely manner, improperly performing craniocervical fusion surgery, inducing a patient to undergo unnecessary tethered cord surgery, and “causing physical, emotional, and financial injuries,” among other allegations. Malpractice lawsuits are common for neurosurgeons, as it is considered a high-risk specialty.

Colleagues have stressed that Bolognese takes risks to help a group of patients with unique challenges. “Bolognese is doing risky surgery in a group that has a high probability of complications,” said Kaufman.

Bolognese has found it challenging to present “in a convincing way, this new sub, sub sub sub discipline, to colleagues.”

The future of CCI

In 2019, Brea connected Bolognese with the Open Medicine Foundation, a nonprofit group supporting people with ME and other complex chronic illnesses. He began speaking at their meetings every other month. At first, some OMF trustees resisted the idea that symptoms could be cured with neurosurgery, Bolognese recalled. Today, “most” accept that a minority of ME patients have CCI, he said, though they agree that surgery “should not be considered as a panacea.” 

With millions of Americans impacted by Long COVID, ME has recently gained recognition. A recent Long COVID study funded by the NIH found that ME is more likely after a SARS-CoV-2 infection. 

Some researchers have already begun tackling these interconnected conditions. Beth Pollack, a biomedical researcher at MIT who focuses on ME, Long COVID, and other complex chronic illnesses, chaired the first-ever NIH webinar discussing connective tissue disorders in ME in January 2024. Connective tissue disorders and spinal conditions are now included as part of the NIH’s 2024 ME/CFS research roadmap, a national research research plan. Pollack is planning several other research projects, pending funding. 

More work is on the horizon. Physician education talks from the CDC-sponsored Project ECHO include a connective tissue and spinal disorders component. The Medical University of South Carolina is building a new EDS multidisciplinary spinal center. And Harvard scientists are studying CCI and using stem cells to regenerate connective tissues. 

“People’s spines are falling apart,” Pollack said. “We need to understand what’s driving the connective tissue and spine damage, so that we can noninvasively predict, prevent and treat patients before they develop these severe conditions.”

Brea, who is currently working on a documentary about her craniocervical fusion surgery, said awareness of ME and related conditions has grown since Unrest came out nearly a decade ago. “With that, some of the old stereotypes are dying,” Brea said. While most doctors still don’t know how to diagnose or treat patients, she added, that will change. “It starts with that awareness among the public and patients that then spills over into the medical system.”

People’s spines are falling apart … We need to understand what’s driving the connective tissue and spine damage so that we can noninvasively predict, prevent and treat patients before they develop these severe conditions.

Beth Pollack

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Colleen de Bellefonds is a freelance science journalist. She lives in Paris with her French husband, dog, and two Franco-American kids; follow her on X at @ColleenCNYC or Bluesky at @ColleenDB.

Editor’s note, April 23, 12 PM Eastern: The headline was adjusted and small changes made in the text to more accurately reflect the relationship between ME and CCI and add context about malpractice lawsuits.

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