The pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is unknown. In this study, we test the hypothesis that hypermobility, signs of intracranial hypertension (IH), and craniocervical obstructions may be overrepresented in patients with ME/CFS and thereby explain many of the symptoms. Our study is a retrospective, cross-sectional study, performed at a specialist clinic for referred patients with severe ME/CFS as defined by the Canada Consensus Criteria. The first 272 patients with ME/CFS were invited to participate, and 229 who provided prompt informed consent were included. Hypermobility was assessed using the Beighton Score. IH was assessed indirectly by the quotient of the optic nerve sheet diameter (ONSD)/eyeball transverse diameter on both sides as measured on magnetic resonance imaging (MRI) of the brain. We also included assessment of cerebellar tonsil position in relation to the McRae line, indicating foramen magnum. Craniocervical obstructions were assessed on MRI of the cervical spine. Allodynia was assessed by quantitative sensory testing (QST) for pain in the 18 areas indicative of fibromyalgia syndrome (FMS). A total of 190 women, mean age 45 years, and 39 males, mean age 44 years, were included. Hypermobility was identified in 115 (50%) participants. MRI of the brain was performed on 205 participants of whom 112 (55%) had an increased ONSD and 171 (83%) had signs of possible IH, including 65 (32%) who had values indicating more severe states of IH. Cerebellar tonsils protruding under the McRae line into the foramen magnum were identified in 115 (56%) of the participants. MRI of the cervical spine was performed on 125 participants of whom 100 (80%) had craniocervical obstructions. Pain at harmless pressure, allodynia, was found in 96% of the participants, and FMS was present in 173 participants or 76%. Compared to a general population, we found a large overrepresentation of hypermobility, signs of IH, and craniocervical obstructions. Our hypothesis was strengthened for future studies on the possible relation between ME/CFS symptoms and hypermobility, IH, and craniocervical obstructions in a portion of patients with ME/CFS. If our findings are confirmed, new diagnostic and therapeutic approaches to this widespread neurological syndrome should be considered.

Hypnosis is a powerful tool in pain therapy. Attempting to elucidate cerebral mechanisms behind hypnotic analgesia, we measured regional cerebral blood flow with positron emission tomography in patients with fibromyalgia, during hypnotically-induced analgesia and resting wakefulness. The patients experienced less pain during hypnosis than at rest. The cerebral blood-flow was bilaterally increased in the orbitofrontal and subcallosial cingulate cortices, the right thalamus, and the left inferior parietal cortex, and was decreased bilaterally in the cingulate cortex. The observed blood-flow pattern supports notions of a multifactorial nature of hypnotic analgesia, with an interplay between cortical and subcortical brain dynamics. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

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BackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease considered to be triggered by viral infections in a majority of cases. Symptoms overlap largely with those of post-acute sequelae of COVID-19/long-COVID implying common pathogenetic mechanisms. SARS-CoV-2 infection is risk factor for sustained latent virus reactivation that may account for the symptoms of post-viral fatigue syndromes. The aim of this study was first to investigate whether patients with ME/CFS and healthy donors (HDs) differed in their antibody response to mild/asymptomatic SARS-CoV-2 infection. Secondly, to analyze whether COVID-19 imposes latent virus reactivation in the cohorts.MethodsAnti-SARS-CoV-2 antibodies were analyzed in plasma and saliva from non-vaccinated ME/CFS (n=95) and HDs (n=110) using soluble multiplex immunoassay. Reactivation of human herpesviruses 1-6 (HSV1, HSV2, VZV, EBV, CMV, HHV6), and human endogenous retrovirus K (HERV-K) was detected by anti-viral antibody fingerprints in saliva.ResultsAt 3-6 months after mild/asymptomatic SARS-CoV-2 infection, virus-specific antibodies in saliva were substantially induced signifying a strong reactivation of latent viruses (EBV, HHV6 and HERV-K) in both cohorts. In patients with ME/CFS, antibody responses were significantly stronger, in particular EBV-encoded nuclear antigen-1 (EBNA1) IgG were elevated in patients with ME/CFS, but not in HDs. EBV-VCA IgG was also elevated at baseline prior to SARS-infection in patients compared to HDs.ConclusionOur results denote an altered and chronically aroused anti-viral profile against latent viruses in ME/CFS. SARS-CoV-2 infection even in its mild/asymptomatic form is a potent trigger for reactivation of latent herpesviruses (EBV, HHV6) and endogenous retroviruses (HERV-K), as detected by antibody fingerprints locally in the oral mucosa (saliva samples). This has not been shown before because the antibody elevation is not detected systemically in the circulation/plasma.

To study the CNS in chronic muscular pain typical of fibromyalgia we compared PET measures of regional cerebral blood flow (rCBF) in eight fibromyalgic patients and controls at rest. Higher rCBF for patients than controls was found bilaterally in the retrosplenial cortex. Lower rCBF for patients than controls were seen in the left frontal, temporal, parietal, and occipital cortices. The higher retroplenial rCBF in patients than controls may reflect increased attention towards sub-noxious somatosensory signaling, and agrees with the notion that fibromyalgic pain reflects secondary hyperalgesia. The brain regions with lower rCBF in fibromyalgic patients than controls participate in the normal cognitive processing of pain, which may be dysfunctional in fibromyalgia.