Tag: progression of illness

Significant aggravation of pre-existing myalgic encephalomyelitis/chronic fatigue syndrome following proton beam therapy for sphenoid wing meningioma: case report

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem disorder characterized by profound fatigue, post-exertional malaise (PEM), immune dysregulation, and mitochondrial dysfunction. While radiation exposure has been linked to fatigue syndromes with overlapping pathophysiology, no previous reports have described the effects of therapeutic radiation, including proton beam radiotherapy (PBRT), in patients with ME/CFS.

Case presentation: We report the case of a 46-year-old woman with a pre-existing, clinically confirmed diagnosis of ME/CFS (Bell score 60, ECOG 1), who underwent postoperative PBRT (50.4 Gy in 28 fractions) for a recurrent left sphenoid wing meningioma (CNS WHO grade 1). The tumor had been surgically resected but showed residual disease with early postoperative progression and close proximity to the left optic nerve, prompting the indication for adjuvant radiotherapy. The patient initially tolerated treatment well, with only mild acute worsening of pre-existing fatigue and transient corticosteroid-responsive symptoms. However, within weeks of completing radiotherapy, she developed progressive and severe worsening of fatigue, myalgia, vertigo, and hypersensitivity to sensory stimuli as well as cognitive decline. Over several months, she became completely bedridden (Bell score 0, ECOG 4) with persistent ME/CFS aggravation unresponsive to supportive measures persisting until the last known contact 20 months after radiation. Follow-up imaging showed stable postoperative findings without tumor progression or new structural brain lesions.

Discussion: This case illustrates a profound and irreversible deterioration of ME/CFS following PBRT, suggesting that radiation-induced mitochondrial dysfunction, oxidative stress, and chronic inflammatory activation may critically worsen pre-existing metabolic fragility. Despite the theoretical advantages of proton radiotherapy in reducing normal tissue exposure, its protective effects may be insufficient in patients with baseline mitochondrial malfunction.

Conclusion: This is, to our knowledge, the first reported case of severe and sustained ME/CFS exacerbation after radiotherapy. The case emphasizes the urgent need for risk stratification, tailored consent processes, and research in the field of radiotherapy tolerance in ME/CFS patients, as conventional expectations regarding side effects may not predict outcomes in this vulnerable population.

Source: Fischer C, Seidlitz A, Krause M. Significant aggravation of pre-existing myalgic encephalomyelitis/chronic fatigue syndrome following proton beam therapy for sphenoid wing meningioma: case report. Strahlenther Onkol. 2026 Jun 11. doi: 10.1007/s00066-026-02553-w. Epub ahead of print. PMID: 42277311. https://link.springer.com/article/10.1007/s00066-026-02553-w (Full text)

How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS

Abstract:

We propose a framework for understanding and interpreting the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) that considers wider determinants of health and long-term temporal variation in pathophysiological features and disease phenotype throughout the natural history of the disease. As in other chronic diseases, ME/CFS evolves through different stages, from asymptomatic predisposition, progressing to a prodromal stage, and then to symptomatic disease. Disease incidence depends on genetic makeup and environment factors, the exposure to singular or repeated insults, and the nature of the host response. In people who develop ME/CFS, normal homeostatic processes in response to adverse insults may be replaced by aberrant responses leading to dysfunctional states.

Thus, the predominantly neuro-immune manifestations, underlined by a hyper-metabolic state, that characterize early disease, may be followed by various processes leading to multi-systemic abnormalities and related symptoms. This abnormal state and the effects of a range of mediators such as products of oxidative and nitrosamine stress, may lead to progressive cell and metabolic dysfunction culminating in a hypometabolic state with low energy production.

These processes do not seem to happen uniformly; although a spiraling of progressive inter-related and self-sustaining abnormalities may ensue, reversion to states of milder abnormalities is possible if the host is able to restate responses to improve homeostatic equilibrium. With time variation in disease presentation, no single ME/CFS case description, set of diagnostic criteria, or molecular feature is currently representative of all patients at different disease stages. While acknowledging its limitations due to the incomplete research evidence, we suggest the proposed framework may support future research design and health care interventions for people with ME/CFS.

Source: Nacul L, O’Boyle S, Palla L, et al. How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS. Front Neurol. 2020;11:826. Published 2020 Aug 11. doi:10.3389/fneur.2020.00826 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431524/ (Full text)

Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome

Abstract:

Natural killer (NK) cell activity was measured blindly in vitro with blood specimens from 50 healthy individuals and 20 patients with clinically defined chronic fatigue immune dysfunction syndrome (CFIDS) who met the criteria established by the Centers for Disease Control and Prevention (Atlanta).

In accordance with a group scoring system of 1-10 points, with 10 being the most severe clinical status, the patient population was stratified into three clinical groups: A (> 7 points), B (5-7 points), and C (< 5 points). NK cell activity was assessed by the number of lytic units (LU), which for the 50 healthy controls varied between 20 and 250 (50%, 20-50 LU; 32%, 51-100 LU; 6%, 101-130 LU; and 12%, > 150 LU).

In none of the 20 patients with CFIDS was the NK cell activity > 100 LU. For group C, the 10 patients stratified as having the least severe clinical condition, the measure was 61.0 +/- 21.7 LU; for group B (more severe, n = 7), it was 18.3 +/- 7.3 LU; and for group A (most severe, n = 3), it was 8.0 +/- 5.3 LU.

These data suggest a correlation between low levels of NK cell activity and severity of CFIDS, which, if it is confirmed by additional studies of larger groups, might be useful for subgrouping patients and monitoring therapy and/or the progression of CFIDS.

 

Source: Ojo-Amaize EA, Conley EJ, Peter JB. Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S157-9. http://www.ncbi.nlm.nih.gov/pubmed/8148445