This case series describes three young women with moderately severe ME/CFS and one- or two-level cervical canal stenosis. Their narrowest AP cervical canal diameters were between 6 and 8.5 mm. Surgical management was associated with a marked improvement in myelopathic symptoms, resolution of lightheadedness and hemodynamic dysfunction, improvement in activity levels, and improvement in global ME/CFS symptoms. In the absence of evidence from randomized trials, we cannot exclude a coincidental improvement or a placebo response to surgery. However, we consider this less likely given the myelopathic examination findings, the demonstration of spinal cord compression on MRI scans, and the lack of a placebo response to multiple previous interventions that included cognitive behavioral and psychiatric treatment. The prompt post-surgical restoration of more normal function instead suggests that the spinal cord compression had a causal role in symptoms, and emphasizes the importance of a careful search for myelopathic examination findings in those with ME/CFS, especially when individuals with severe impairment are not responding to treatment.

The diagnosis of cervical stenosis in all three patients was delayed for several years. In patient 1, who had cervical spondylosis superimposed on congenital cervical stenosis, an overlooked historical clue to her diagnosis was the history of congenital cervical stenosis in her mother. Patient 1′s deep tendon reflexes were never brisk, and her Hoffman sign was only positive after several years of normal neurological exam findings. The Hoffman sign is present in a variable proportion of those with cervical myelopathy, appearing earlier in myelopathy than the Babinski sign [26]. While it can be detected in healthy individuals, among 16 adults with positive Hoffman signs and no cervical symptoms, 15 (94%) had evidence of cord compression on MRI [27]. It is possible that the Hoffman sign would have been more consistently abnormal in patient 1 if it had been elicited after multiple flexion and extension movements of the neck as described by Dennow and Meadows [28].

The other two patients had consistently pathological neurological examination findings. Both had brisk deep tendon reflexes, one with ankle clonus and the other with a positive Hoffman sign. Both individuals had been evaluated by more than one experienced neurologist, and the reflex findings had been attributed to non-pathological or psychosomatic causes. We speculate that a negative bias toward the ME/CFS label and the presence of co-morbid anxiety may have distracted attention from the neurological findings. Of interest, all 3 patients reported less anxiety in daily life after surgery, and all were able to reduce or eliminate their anti-anxiety medication. A reduction in anxiety following cervical decompression has been reported elsewhere [29].

Our findings are consistent with the observations of Heffez and colleagues in adults with fibromyalgia [30], a condition with a substantial symptom overlap with ME/CFS [31]. Among 270 adults referred to evaluate whether there was a neurological basis for their fibromyalgia symptoms (none of whom had previously been diagnosed with a cervical myelopathy), myelopathic symptoms included neck/back pain (96%), instability of gait (86%), subjective grip weakness (83%), paresthesias (80%), dizziness (71%), and numbness of the hands and feet (69%). Hyper-reflexia was identified in 64%, a positive Romberg sign in 28%, a positive Hoffman sign in 26%, ankle clonus in 25%, and impaired tandem walk in 23%. The AP spinal canal diameter at the level of the C5/6 intervertebral disc measured 10 mm or less in 46% of participants [30]. A subset of this cohort underwent treatment of cervical myelopathy by surgical (N = 40) or non-surgical (N = 31) means [29]. The surgical group was not restricted to those with cervical spine stenosis alone, as an unreported number underwent posterior fossa decompression for Chiari malformation. There were no baseline differences in symptom prevalence at baseline, and neurologic signs were similar between the surgical and non-surgical patients. As expected, the patients in the surgical group had a narrower mid-sagittal spinal canal diameter at C5/6 and C6/7. At the 1-year follow-up, those in the surgical group experienced a significant improvement in all symptoms attributed to fibromyalgia (including fatigue, impaired concentration, and body pain), significantly higher quality of life scores on the SF-36 physical and mental health subscales, and significant improvement in depression and anxiety scores. Holman has also reported intermittent cervical cord compression with flexion and extension MRI studies in 71% of fibromyalgia patients [32]. While referral bias in those studies does not allow an estimate of the prevalence of cervical myelopathy in unselected fibromyalgia patients, these studies confirm that a subset of individuals with fibromyalgia, many of whom also meet criteria for ME/CFS [31], have potentially treatable cervical myelopathy or dynamic cervical cord compression. Our series extends these observations to those whose symptoms are dominated more by profound fatigue, post-exertional worsening of symptoms, and autonomic dysfunction, and less by widespread pain.

Of interest, all three patients in our series had potentially pathological clivo-axial angles. The decision was made to operate on the bulging cervical discs as a first step, as it was the least invasive surgical intervention. After 32–70 months of follow-up there has been no need for further surgery. We are unsure whether the combined presence of abnormal clivo-axial angle and cervical canal stenosis poses a greater risk of neurological symptoms, but this possibility should be kept in mind in future investigations, especially in light of the observation than an abnormal clivo-axial angle is capable of causing deformative stress within the spinal cord [20].

Our paper also draws attention to the potential for neurally mediated syncope and POTS to be associated with cervical myelopathy. Both hemodynamic abnormalities are strongly associated with ME/CFS [1, 33, 34], and treatment of the orthostatic intolerance can lead to improvements in ME/CFS symptoms and function [33]. One limitation of this series is that the standing tests were performed at varying intervals after surgery. Given the positive impact of exercise on improving orthostatic tolerance in those with POTS [35], we cannot be certain that the improvements in heart rate response during standing were related primarily to the cervical decompression or to the advancement of exercise. However, all three patients reported improvements in lightheadedness and tolerance of upright posture with the first week of surgery, suggesting that the improvement in circulatory symptoms preceded and likely enabled the improvement in activity.

The global improvements noted following surgical decompression in these three patients would suggest a neurological basis of many of their ME/CFS symptoms. Recent research has proposed that ME/CFS symptoms might be related to central nervous system inflammation, central sensitivity, or reduced cerebral blood flow [36,37,38]. The mechanism by which cervical cord compression could influence these putative mechanisms of ME/CFS symptom generation is unclear, but other work has shown that application of a longitudinal neural strain using a passive straight leg raise can increase the intensity of fatigue, pain, headaches, cognitive dysfunction, and lightheadedness in those with ME/CFS [39]. These findings would be relevant given the increased biomechanical strain within the cord that can occur with cervical spondylosis [14, 15]. Subclinical autonomic nervous system dysfunction has been described among those with compressive cervical myelopathy [40]. Because autonomic fibers also traverse through the spinal cord, Srihari and colleagues have proposed that autonomic involvement in compressive cervical myelopathy should be expected. They hypothesize that cervical decompression can lead to improvement in symptoms by reducing cord edema, improving venous drainage, and improving cord perfusion [40]. Hoshimaru has hypothesized that improvements in neuropsychological function among patients with cervical spondylotic myelopathy after decompression surgery could be related to improvement in cerebrospinal flow within the spinal canal, which in turn would be expected to lead to improvement in cerebral blood flow [41]. These mechanisms would also be potential contributors to changes in ME/CFS and autonomic symptoms.

This case series emphasizes an overlap in certain symptoms of ME/CFS and myelopathy. The extent of that overlap will require more attention to the systemic symptoms of those with traditional cervical myelopathy (who do not have a diagnosis of ME/CFS), and to the myelopathic symptoms and exam findings of those with ME/CFS. Although cervical stenosis does not appear to be a common abnormality among those with ME/CFS, its prevalence has not been the subject of formal study. We would expect cervical stenosis to be more common among those with more severe forms of the illness. The presence of myelopathic symptoms and signs warrants further radiologic investigation, after which care will need to be taken to define the optimal candidates for surgical decompression. This case series establishes the potential for spondylotic cervical myelopathy to contribute in an important way to symptoms in a subset of those with moderate to severe ME/CFS and orthostatic intolerance. It will be worthwhile to investigate these observations further in larger prospective studies. To evaluate more definitively whether cervical spinal stenosis can cause ME/CFS symptoms will require a randomized trial of surgery in individuals with ME/CFS who are found on further investigation to have cervical spinal stenosis and classical indications for cervical decompression surgery.