A significant step towards understanding the enigmatic chronic fatigue syndrome (ME/CFS) has been taken. Published in Nature Communications, a new study delves deeper than any before, offering a multifaceted perspective on this condition that often leaves patients feeling unheard and their symptoms dismissed.
ME/CFS manifests as crippling fatigue, often exacerbated even by minimal exertion. Many patients struggle to find proper diagnosis and care, enduring dismissals that their symptoms are "imagined." This new research, led by Dr. Avindra Nath, Director of the National Institute of Neurological Disorders and Stroke, firmly establishes ME/CFS as a biological reality. The study compared 17 ME/CFS patients with 21 healthy individuals, revealing distinct brain activity, along with immune system and other abnormalities in the patient group.
The research team, comprising over 75 scientists and costing over $8 million, highlights the complexity of studying ME/CFS systematically. Jo Cambridge, an immunologist at University College London (UCL), acknowledges that the paper "brings together the complexity" of the condition, emphasizing the intricate web of factors researchers must account for.
However, the extensive time required for this study underscores the challenges associated with research into ME/CFS. Brian Vastag, a former science journalist affected by ME/CFS who was instrumental in getting the study started and even participated in it himself, emphasizes the need for accelerated progress. "This must be the beginning of building a bigger research program," he emphasizes.
Recruitment presented a significant hurdle initially. Focusing only on patients whose symptoms arose after a viral or bacterial illness, Dr. Nath's team excluded those with pre-existing conditions to avoid skewing results. They meticulously evaluated medical records and interviewed over 200 potential participants before inviting 27 to the National Institutes of Health (NIH) for extensive medical tests.
This meticulous evaluation revealed a concerning reality: several participants received inaccurate diagnoses, even including potentially life-threatening conditions like cancer and pulmonary embolism. These missed diagnoses underscore the inadequate care many ME/CFS patients experience, echoing many patients' lived experiences. "It speaks volumes about the shortcomings of our medical system that they had to participate in a research study to discover what was truly ailing them," states Mike VanElzakker, a neuroscientist at Massachusetts General Hospital.
The NIH participants underwent a comprehensive week-long evaluation encompassing skin and muscle biopsies, spinal taps, and energy expenditure measurements. Despite extensive investigations, researchers found no muscular abnormalities in ME/CFS patients that could solely explain their post-exertional fatigue. Additionally, cognitive and psychiatric assessments revealed no significant differences between the groups.
However, functional magnetic resonance imaging (fMRI) unveiled decreased activity in specific brain regions involved in, among other functions, movement control. Researchers posit that these brain signals function like "stop signs" hindering physical activity, akin to an illness forcing an individual to rest. "When we have a severe flu, we're incapable of getting out of bed," explains Jonathan Edwards, a rheumatologist at UCL. "This signifies a central signaling problem in the brain, not muscular issues," he clarifies.
Nancy Klimas, Director of the Institute for Neuro-Immune Medicine at Nova Southeastern University, emphasizes that the study's key takeaway points towards ME/CFS being "a disease of the brain ... the sustained energy deficit originates from this very organ." However, the reason behind the persistence of this abnormal signaling remains an enigma. While the researchers found no traces of lingering pathogens, such detection can be challenging.
Furthermore, the study identified additional biological discrepancies between the groups, echoing findings from previous research. Notably, ME/CFS patients demonstrated higher heart rates and delayed blood pressure normalization after exertion, indicating abnormalities in the autonomic nervous system. Additionally, their cerebrospinal fluid displayed elevated levels of the protein PD-1 in T cells, suggesting these immune cells were attempting to fight an unidentified threat.
Connecting these dots, Dr. Nath and his colleagues theorize that immune dysfunction might be triggering the brain abnormalities observed. He proposes that medications known as checkpoint inhibitors, which currently aid the immune system in combating cancer, could potentially revitalize exhausted T cells in ME/CFS patients. He expresses hope that a new wave of Long Covid studies might offer further insights into ME/CFS, acknowledging the potential overlap in symptoms, although the extent of their biological connection remains unclear.
While acknowledging the significance of the research, Vastag, whose partner Beth Mazur lost her life to suicide due to ME/CFS in December 2023, ponders whether a different approach may have yielded quicker results. "She lost hope of ever feeling better," he shares. "Prompt action based on these findings is crucial, as the ME/CFS community desperately needs answers and solutions."
