How infection can damage the cervical spine

How could post-infectious ME result from pathologies like CCI or cervical stenosis? There are precedents. Here are three examples from elsewhere in the medical literature of how infection can damage the cervical spine and cause brainstem compression

My last two pieces explored the possible relationship between brainstem compression and dysautonomia, and how compression, stretch, or deformation of nerve tissue can cause ischemia (low blood flow) to the brain and spinal cord. This ischemia in turn results in a host of downstream metabolic consequences like low oxygen, a switch to anaerobic metabolism, increased lactate, and inflammation. I hypothesized that these metabolic consequences could actually constitute (be one in the same as) post-exertional malaise (PEM). And that my dysautonomia and PEM were a product of the three spinal pathologies for which I had surgery: craniocervical instability (CCI), atlantoaxial instability (AAI), and tethered cord syndrome.

Next, I was going to write about how the symptoms of “brain fog,” cognitive dysfunction, and cognitive PEM fit into this model. I’m gonna give you a spoiler. I think these symptoms could all be caused by intracranial hypertension, that is, elevated pressure in the skull. Just as tethered cord syndrome can result in reduced blood flow to the spine, intracranial hypertension can cause reduced blood flow to the brain and all its downstream metabolic effects (low oxygen, a switch to anaerobic metabolism, increased lactate, and inflammation). This is actually what happens in early traumatic brain injury (TBI), when swelling of the brain results in reduced blood flow, and may be why the pathophysiology of TBI and the pathophysiology of Myalgic Encephalomyelitis (ME) share a lot in common.

In fact, a growing number of clinicians think intracranial hypertension may be an important part of the pathophysiology of both chronic fatigue syndrome and fibromyalgia (that research summarized here). This elevated intracranial pressure can have many causes, among them Chiari malformation, craniocervical instability, atlantoaxial instability, severe cervical stenosis, and vascular stenosis (of the jugular veins or transverse sinuses).

That is not what I’m going to talk about today, though, because that topic is really, really complicated. It’s literally a fluid system, of brain, blood, and cerebrospinal fluid, that can have very different dynamics depending on the pathology. I’ll go deep on it one day, when I learn more, but at least now you know what my hunch is.

What I want to revisit in this piece is the role of infection in all this. I have previously described how genetic risks, like Ehlers-Danlos Syndrome, and many environmental risks, like viral infection, bacterial infection, mold exposure and fluroquinolone antibiotics, but also sex hormones, can alter connective tissue integrity and potentially contribute to CCI/AAI.

The idea that the pathology of post-infectious ME (the pathology being the damage caused by the infection) could be one of several varieties of damage to the cervical spine is, I admit, a bit difficult to wrap one’s head around. This is especially true if you are wondering how very small things might relate to gross anatomy. How, for example, could factors as tiny as bacteria and viruses reshape our body’s structure? Of the risk factors mentioned above, however, infection is actually the one risk factor of cervical damage that has the most support in the medical literature. Here are three known models of post-infectious cervical pathology.

Tuberculosis can cause craniocervcial instability (CCI)

First, tuberculosis infection can cause craniocervical instability. It is not CCI of the type I had: mine was a product of ligament laxity. Rather, tuberculosis can cause CCI by triggering an inflammatory process that erodes bone. The result can be brainstem compression and myelopathy. Treatment involves administering antibiotics for the infection itself and providing conservative immobilization (i.e., a cervical collar), but many cases require posterior fusion, the same surgery I had.

Brucellosis can cause cervical spondylitis and stenosis

Florence Nightingale, as we all know, is a touchstone for people with ME. She contracted Brucellosis, a bacterial infection, while serving as a nurse in the Crimean War and never recovered. She had many symptoms we would recognize today as symptoms of ME. Her birthday, May 12th, is the international awareness day for ME, along with fibromyalgia, chronic Lyme disease, Gulf War illness, mold illness, multiple chemical sensitivity, and post-sepsis syndrome.

“In 1854, from the age thirty-five to sixty-years, Florence Nightingale was reported as suffering from chest pains, headaches, rapid muscle fatigue, persistent upper back pain, and being unable to concentrate if more than one person was present.”

In a group of people with ME currently investigating the role of structural or mechanical diagnoses in their condition, cervical stenosis, a narrowing of the cervical vertebral canal, is cropping up as the third most common diagnosis. If severe enough, stenosis can impinge spinal fluid flow and compress the spinal cord. A recent case series by Peter Rowe of three ME patients with cervical stenosis found significant improvement or remission of symptoms following surgery.

In turns out Brucellosis infection can cause spondylitis, an inflammation of the vertebrae that can lead to spinal stenosis. A multi-center study of 593 brucellosis patients found that 9.7% (58) developed spondylitis as a complication of their brucellosis. Of these, seven patients had spondylitis of the cervical spine, five of them with neurological involvement, namely compression of the medulla (brainstem) or roots.

In short: brucellosis can cause brainstem compression.

We can never know what Florence Nightingale actually had or why she never recovered from her brucellosis infection. Some historians have speculated it was due to hysteria or some kind of psychological disorder. Maybe the brucellosis just damaged her cervical spine. At least, I like that hypothesis better.

Upper respiratory infections can cause atlantoaxial instability (AAI)

The last example is a rare condition called Grisel’s Syndrome. First documented in the 1830s, it is a form of non-traumatic atlantoaxial instability that generally occurs after an upper respiratory infection. It can also develop following post-operative inflammation in susceptible individuals. (Could this be what happened to me after my thyroid surgery?) Children are thought to be more susceptible because their atlantoaxial joint, specifically the transverse ligament, is naturally more lax. Children with Down Syndrome are also more susceptible. I wonder if people with connective tissue disorders like Ehlers-Danlos Syndrome or Marfan Syndrome are as well. Its most obvious sign is torticollis, a stiff, turned neck.

Treatments include addressing the infection, administering anti-inflammatories, immobilization the neck (e.g., via a cervical collar), and…bedrest. “Early treatment is crucial to prevent long-term sequelae.” If Grisel’s syndrome is detected and treated early, surgical fusion can usually be avoided.

The closest analogy to my form of cervical pathology, CCI/AAI, is Grisel’s syndrome. I can’t help but wonder if at the time of my viral onset, had I addressed the inflammation (in my case due primarily to mast cell activation syndrome); taken antivirals much earlier (every time I had an HSV-1 outbreak, I would have a stiff neck and pain in the back of my skull); aggressively rested; and protected my neck, might have I avoided the long-term sequelae that came in full force 18 months later, the cluster of symptoms that we call ME?

The best evidence, albeit scant and indirect, of a possible connection between ME and the kind of post-infectious cervical damage we see in Tuberculosis, Brucellosis, and Grisel’s Syndrome comes from the pre-1984 ME outbreaks themselves. These case reports mention symptoms that have been largely forgotten by contemporary definitions of the disease. They provide clues as to the kind of damage some ME patients may have suffered as a result of their infections.

Radiculopathy is the medical term for a “pinched nerve.” Radiculopathies usually originate in the spine, at the nerve root, but can cause symptoms in distant parts of the body which the compressed nerve enervates. The parts of the body where symptoms might appear depend on which levels of the spine are affected.

A study conducted between 1948 and 1952 of 21 patients who had become ill during the 1934 Los Angeles County Hospital Outbreak found via electromyogram evidence of radiculopathy. In other words, patients who failed to recover following the LA outbreak had signs of nerve compression. Ulnar neuritis was mentioned in several outbreaks. However, ulnar neuritis is frequently confused with lower cervical (C8-T1) radiculopathy, which has similar symptoms. Ramsay reported that 61% of his patients had numbness or abnormal sensation, which could also be due to radiculopathy. This all suggests that whatever might be happening in the brain or brainstem, some patients may have problems in lower levels of their spine, possibly as a result of mechanical compression of the spinal cord and/or the nerves that branch from it.

If tubercular craniocervical instability, Brucellosis spondylitis, Grisel’s syndrome and their resulting brainstem/spinal compression prove to be apt models for our post-infectious disease, ME, it implies several possibilities:

1. This disease is heterogenous in at least two ways: the same infection may cause different types of damage in different people; different infections may cause the same type of damage in different people.
2. Effective prevention and treatment requires accurately identifying all the possible varieties of damage and understanding the disease processes that can generate them.
3. Myalgic Encephalomyelitis was a remarkably prescient name for this disease in many ways. However, the problem may not be within the nerve tissue itself but rather in the structures that surround it. If true, that would be very good news.
4. This disease model/hypothesis is imminently testable. However, to properly test it, we cannot treat all patients who meet ME criteria as the same.

70% of 70 ME patients on Twitter who have gotten imaging and pursued diagnosis with a neurosurgeon reported that they did in fact receive a diagnosis of one or more mechanical or structural craniocervical junction or spinal conditions. On my Facebook page, 79% of 184 respondents reported the same. 75.8% of 66 patients on Phoenix Rising who pursued testing reported they have been diagnosed with Chiari, CCI, AAI, or cervical stenosis.

These online polls likely overestimate the true proportion of our patient population who have these conditions. After all, people with neck pain or coat hanger pain; or who have pressure in their head or pain behind their eyes; who experience numbness, tingling, or weakness; or who notice their symptoms get worse when they lay down; or whose symptoms get worse when they are standing; or who have a history of trauma or surgery are all more likely to pursue diagnosis in the first place. Still, they suggest that a subset of our community are dealing with these issues.

As we continue along this path of inquiry and with the news of a possible clinical trial for craniocervical fusion surgery in Europe, the three above examples help illustrate a very important fact: Craniocervical fusions are not a cure for ME. They are a treatment for people with ME who have craniocervical instabilty. Chiari decompression is not a cure for ME. It is a treatment for people with ME who have Chiari I malformations. Decompressive laminectomies are not a cure for ME. They are one of several possible treatments for people with ME who have cervical stenosis. Stenting the transverse sinuses is not a cure for ME. It is one of several possible treatments for people with ME who have intracranial hypertension and tranverse sinus stenosis. Blood patches are not a cure for ME. They are a treatment for people with ME who have chronic idiopathic cerebrospinal fluid leaks.

What percentage of our patient population these diagnoses capture we do not yet know. I believe it is likely to be a significant subset. It will not, however, be all of us.

These conversations require nuance, specificity and a lot of care. Our task is to find the people who have these spinal complications and to document their prevalence, range of possible causes, and the effects of treatment so that everyone who needs it can have access to diagnosis and the highest possible standard of care. Then, with a clearer focus, we can turn to hunting down the pathology (structural, mechanical, molecular or otherwise) of all the other cases that the above diagnoses cannot explain.

I’m sure there are many other examples of post-infectious cervical pathologies in the medical literature. See if you can find some more!

Read more posts in my CCI + tethered cord series.

Read this disclaimer. Crucially, surgery carries risks and it’s important to remember that in medicine, the same exact symptoms can have multiple, different causes. We have no idea how prevalent CCI is in our community and there’s been no research into its relationship with ME. We do know that it is more common among patients with EDS.