Health Technology Assessments and Government Reports

1 Cornelis et al. 2026 — KCE Belgian ME/CFS Needs Analysis (KCE Report 420)

(Cornelis et al. 2026b)

Full Citation: Cornelis J, De Meulemeester K, Christiaens W, Jonckheer P, Savoye I, Dauvrin M, Kohn L, Castanares-Zapatero D. Management of myalgic encephalomyelitis/chronic fatigue syndrome in Belgium: an analysis based on patient needs. Health Services Research (HSR) Brussels: Belgian Health Care Knowledge Centre (KCE). 2026. KCE Reports 420. DOI: 10.57598/R420C Published: 30 June 2026 Study Design: Mixed-methods health services research (NEED framework) Sample Size: n=749 adult ME/CFS patients (online survey) + 19 semi-structured qualitative interviews

Key Findings:

  • Quality of Life: EQ-5D-5L utility score declined from 0.84 (pre-illness) to 0.36 (current, p \(<\) 0.001) — substantially below Belgian general population mean of 0.79
  • Symptoms: Abnormal fatigue (98.7%), PEM (97.7%), sleep disorders (97.2%) reported by nearly all respondents; >75% rated these very/extremely burdensome
  • Comorbidities: Fibromyalgia (63.3%), IBS (56.9%), orthostatic hypotension (20.6%), POTS (17.0%), long COVID (16.4%), SFN (12.8%), MCAS (10.5%)
  • Diagnostic delay: 50% waited >2 years from first consultation to diagnosis; 39% waited >5 years; delay associated with significantly worse HRQoL (p=0.010)
  • Treatment experiences: GET predominantly perceived as harmful (majority reported PEM exacerbation); CBT mixed (~50% improved, ~20% deteriorated); physiotherapy and psychological counselling generally positive; pacing widely used but evidence base limited
  • Care organisation: Only one NIHDI-funded reference centre in Belgium (Dutch-speaking Flanders); other centres entail out-of-pocket costs; 50% reported care rarely/never well organised
  • Work impact: 1,189 individuals in Belgian invalidity database (31 Dec 2024); mean invalidity duration 8.6 years — among the longest of any condition studied under NEED
  • Social impact: 75% reported negative impact on personal relationships; majority stopped working or reduced hours; majority reported financial difficulties
  • Recognition and stigma: Recognition identified as central unmet need; psychologisation experienced as inequitable care; widespread lack of professional expertise
  • International comparison: Only UK has nationally structured ME/CFS referral pathway; Netherlands launched €28.5M ZonMw 10-year biomedical research programme; Italy has draft legislation under consideration

Recommendations:

  • Strengthen recognition and visibility of ME/CFS among healthcare professionals and the public
  • Improve early diagnosis through enhanced clinical education and training
  • Advance translational research combining clinicians, researchers, and patients
  • Develop structured care pathways with reference centres and multidisciplinary coordination
  • Support workplace adaptations accommodating energy limitations

Conclusion: ME/CFS imposes a multidimensional burden with severe QoL impairment, substantial diagnostic delays, fragmented care structures, and profound socioeconomic consequences. Limited recognition at clinical, institutional, and societal levels remains the major contributor to persistent unmet needs. The UK’s structured national referral pathway and the Netherlands’ research programme offer models for reform.

Limitations: Self-reported diagnoses; sampling via patient associations (selection bias); 88.7% Dutch-speaking vs 11.3% French-speaking; not available in German; under-representation of severe/very severe patients; recall bias for retrospective questions; introduction chapter not a formal systematic review.

Relevance to Paper:

  • Provides first comprehensive Belgian ME/CFS needs assessment with large patient sample
  • EQ-5D-5L utility scores directly comparable to other chronic conditions
  • Treatment experience data supports NICE 2021 reversal on GET and nuanced CBT role
  • International comparison contextualises Belgian service gaps
  • Patient-reported outcome data on pacing, symptom burden, and care access
  • Recognition/stigma qualitative findings align with existing literature on contested illness

Certainty Assessment:

  • Quality: High (validated NEED methodology; mixed methods; patient involvement throughout; international peer review)
  • Sample: Large for needs assessment (n=749); qualitative arm provides depth (n=19)
  • Currency: Very current (June 2026)
  • Limitations: Not a clinical guideline; no intervention-level evidence; Belgium-specific healthcare context
  • Score: 0.75

2 Supplement to KCE Report 420 (KCE Report 420S)

(Cornelis et al. 2026a)

Full Citation: Cornelis J, De Meulemeester K, Christiaens W, Jonckheer P, Savoye I, Dauvrin M, Kohn L, Castanares-Zapatero D. Management of encephalomyelitis/chronic fatigue syndrome in Belgium: an analysis based on patient needs — Supplement. Health Services Research (HSR) Brussels: Belgian Health Care Knowledge Centre (KCE). 2026. KCE Reports 420S. DOI: 10.57598/R420S Published: 30 June 2026

Contents:

  • Full subgroup analysis tables for EQ-5D-5L utility scores by demographic, disease, healthcare, and social variables
  • Dutch vs French-speaking subgroup comparison tables
  • Employment status change subgroup analysis
  • Qualitative analysis of open survey question (n=237 free-text responses) on additional unmet needs
  • Complete literature search strategies for Ovid MEDLINE, Cochrane, CINAHL, Embase, PsycINFO, PEDro
  • List of excluded articles
  • Description of healthcare service studies for severely ill individuals
  • List of consulted international experts
  • Questionnaire on healthcare services for individuals with ME/CFS

Key Supplement Findings:

  • Open question analysis identified recognition as the central unmet need across healthcare, policy, and society
  • Psychologisation of ME/CFS identified as a key contributing factor to misrecognition and stigma
  • Consequences: impacts on diagnosis, available therapies, care accessibility, daily living, work, and psychosocial wellbeing
  • French-speaking participants reported higher unmet needs, lower care satisfaction, and greater accessibility problems vs Dutch-speaking participants
  • Financial difficulties and high social impact strongly associated with stopping work (p \(<\) 0.001)

Relevance: Provides full methodological transparency (search strategies, expert list), detailed subgroup analyses enabling equity-focused interpretation, and qualitative depth on recognition/stigma themes central to ME/CFS patient experience.

3 Campbell et al. 2019 — Shoe Lifts for Leg Length Discrepancy: Systematic Review

  • Full Citation:: Campbell TM, Ghaedi BB, Tanjong Ghogomu E, Welch V. Shoe lifts for leg length discrepancy in adults with common painful musculoskeletal conditions: a systematic review of the literature. Archives of Physical Medicine and Rehabilitation. 2019;100(2):346–357.
  • DOI:: https://doi.org/10.1016/j.apmr.2017.10.027
  • Key Findings::
    • Systematic review of 10 studies (1 RCT, 9 observational) on shoe lifts for LLD-associated morbidities
    • Shoe lifts reduce low back pain and functional disability in adults with LLD
    • Only 1 RCT exists (n=30, crossover design); overall evidence quality is low
    • No study measured fatigue, energy expenditure, or systemic symptom outcomes
  • Conclusion:: Shoe lifts are a low-cost intervention that reduces pain in LLD, but the literature has never examined whether correcting LLD improves fatigue, PEM, or autonomic symptoms.
  • Limitations:: Only 1 RCT; heterogeneous LLD definitions (5–30 mm used as inclusion); no fatigue/energy outcomes; English-only search.

4 Schulte et al. 2010 — Sympathetic Chain Lesions from Anterior Scoliosis Surgery

  • Full Citation:: Schulte TL, Mester B, Oberdiek D, Osada N, Liljenqvist U, Filler TJ, Marziniak M, Bullmann V. Approach-related lesions of the sympathetic chain in anterior correction and instrumentation of idiopathic scoliosis. European Spine Journal. 2010;19(9):1558–1567.
  • DOI:: https://doi.org/10.1007/s00586-010-1455-1
  • Key Findings::
    • 12 of 31 patients (39%) showed sympathetic chain dysfunction after anterior scoliosis surgery, confirmed by sudomotor testing (Ninhydrin sweat test)
    • The sympathetic chain lies directly on the anterolateral surface of thoracic vertebral bodies – it is anatomically exposed to any mechanical disturbance of the thoracic spine
    • Lesions were approach-related (surgical dissection), not disease-related, but demonstrate the chain’s vulnerability at this location
    • Sensory symptoms (warmth, dry skin) persisted in some patients at follow-up
  • Conclusion:: The sympathetic chain is anatomically vulnerable to mechanical perturbation at the thoracic spine level. This establishes a necessary mechanistic precondition: if rotoscoliosis or vertebral rotation could mechanically irritate the chain, autonomic dysfunction would be expected.
  • Limitations:: Surgical not disease-related damage; n=31; no autonomic testing beyond sudomotor function; no fatigue/HRV outcomes.

5 Killian et al. 2017 — Scoliosis in Rett Syndrome: Progression, Comorbidities, Predictors

  • Full Citation:: Killian JT, Lane JB, Lee HS, Skinner SA, Kaufmann WE, Glaze DG, Neul JL, Percy AK. Scoliosis in Rett syndrome: progression, comorbidities, and predictors. Pediatric Neurology. 2017;70:20–25.
  • DOI:: https://doi.org/10.1016/j.pediatrneurol.2017.01.032
  • Key Findings::
    • Multicenter natural history study of 913 females with classic Rett syndrome
    • Severe scoliosis (>=40 deg Cobb angle) in 251 (27%); 168 (18%) required surgical correction
    • Severe MECP2 mutations (R106W, R168X, R255X, R270X, large deletions) predicted worse scoliosis
    • Loss of sitting, ambulation, and hand function associated with severe scoliosis
    • Puberty onset associated with progression
  • Conclusion:: Rett syndrome is a genetic disease with both severe autonomic dysfunction and severe scoliosis, making it a natural model system for studying ANS-spine interactions. The association between MECP2 severity, scoliosis, and motor function loss suggests shared neurological pathways.
  • Limitations:: Rett-specific; no direct ANS-spine interaction data; no fatigue measurement. Cannot distinguish whether scoliosis causes ANS dysfunction or both arise from common MECP2-mediated mechanisms.

6 He et al. 2014 — Autonomic Control of Bone Formation

  • Full Citation:: He JY, Zheng XF, Jiang LS. Autonomic control of bone formation: its clinical relevance. In: Handbook of Clinical Neurology. Vol. 117. Elsevier; 2014:161–171.
  • DOI:: https://doi.org/10.1016/B978-0-444-53491-0.00014-6
  • Key Findings::
    • The sympathetic nervous system regulates bone remodeling via beta-2 adrenergic receptors (beta2-AR) on osteoblasts
    • Sympathetic activation increases RANKL expression → increased osteoclastogenesis → bone resorption
    • Leptin-mediated sympathetic tone links energy metabolism to bone turnover
    • Parasympathetic system opposes sympathetic effects on bone
  • Conclusion:: Establishes a bidirectional relationship between the ANS and skeletal structure. Skeletal asymmetry is not a one-way mechanical problem – the ANS actively remodels bone and spine, creating feedback loops.
  • Limitations:: Review chapter; largely preclinical (mouse models); does not address scoliosis or postural asymmetry directly.

7 Grivas et al. 2026 — Three-Plane Rib Cage Remodeling in Early Scoliosis

  • Full Citation:: Grivas TB, Scoliosis Aetiology Study Group, Hellenic School Scoliosis Screening Group. Three-plane morphological remodeling of the rib cage and spine in early-stage scoliogenesis in idiopathic scoliosis. Studies in Health Technology and Informatics. 2026;337:25–30.
  • DOI:: https://doi.org/10.3233/SHTI260737
  • Key Findings::
    • Thoracic rib cage deformity (rib asymmetry, reduced rib-vertebra angles) PRECEDES spinal curvature in idiopathic scoliosis
    • Asymmetric muscular forces may play a causal role in initiating scoliosis
    • Sagittal plane: subtle thoracic kyphosis reduction is permissive but not initiating
    • “Autonomic nervous system” listed as a keyword suggesting recognition of ANS involvement in scoliogenesis
  • Conclusion:: Scoliosis is primarily a rib cage and trunk asymmetry problem, not just a spinal curvature. The asymmetric muscular forces driving this asymmetry raise the possibility of chronic unilateral muscle overuse with metabolic consequences.
  • Limitations:: Review-level, no new primary data; ANS keyword present but no ANS data; pediatric focus.

8 Gerwin 2005 — Myofascial Pain and Fibromyalgia Perpetuating Factors

  • Full Citation:: Gerwin RD. A review of myofascial pain and fibromyalgia – factors that promote their persistence. Acupuncture in Medicine. 2005;23(3):121–134.
  • DOI:: https://doi.org/10.1136/aim.23.3.121
  • Key Findings::
    • Identifies mechanical perpetuating factors for chronic regional pain: postural asymmetry, leg length inequality, pelvic obliquity, scoliosis
    • Mechanical asymmetries create sustained abnormal loading of muscles → trigger point formation → chronic pain
    • Perpetuating factors include both mechanical and systemic (nutritional, metabolic, endocrine) contributors
    • Treatment must address mechanical factors alongside systemic ones
  • Conclusion:: Postural asymmetry is a recognized perpetuating factor in chronic pain syndromes. The hypothesis that it could also drive fatigue syndromes through the same chronic-compensatory-muscle-overload mechanism is a logical extension – but remains untested.
  • Limitations:: Narrative review; no primary data; published 2005; does not address ME/CFS specifically; the extension from pain→fatigue is inferential.

9 Chu and Al Zoubi 2023 — Post-Polio Syndrome with Neck Extensor Myopathy

  • Full Citation:: Chu ECP, Al Zoubi F. Post-polio syndrome presenting as isolated neck extensor myopathy: a case report. AME Case Reports. 2023;7:17.
  • DOI:: https://doi.org/10.21037/acr-22-76
  • Key Findings::
    • Single case: 72-year-old male with prior polio, progressive neck weakness over 2 years
    • Neck MRI showed atrophy of cervical paraspinal muscles, kyphotic deformity
    • Diagnosis: post-polio syndrome with scoliosis and isolated neck extensor myopathy
    • Managed conservatively with physiotherapy
  • Conclusion:: Demonstrates that skeletal deformity (scoliosis, kyphosis) can co-occur with progressive muscle fatigue in neurological disease. Limited generalizability as n=1.
  • Limitations:: Single case report; no mechanistic investigation; PPS is a distinct disease; cannot separate PPS-specific mechanisms from mechanical effects of deformity.

10 Jubelt 2004 — Post-Polio Syndrome Review

  • Full Citation:: Jubelt B. Post-polio syndrome. Current Treatment Options in Neurology. 2004;6(2):105–113.
  • DOI:: https://doi.org/10.1007/s11940-004-0018-3
  • Key Findings::
    • PPS fatigue mechanism: metabolic exhaustion of surviving motor neurons that overworked for decades compensating for lost motor units
    • This “compensatory overuse → metabolic failure” model is the dominant PPS fatigue hypothesis
    • PPS patients also have scoliosis, joint deformities, and mechanical asymmetry from childhood polio
    • Treatment: energy conservation, pacing, lifestyle modification – same principles as ME/CFS management
  • Conclusion:: PPS provides precedent for fatigue arising from chronic compensatory muscular work – if a mechanical asymmetry creates sustained unilateral muscle overwork over years/decades, the resulting metabolic exhaustion could produce a fatigue syndrome with similar features to PPS. This is the strongest indirect precedent for the compensatory-overuse limb of the skeletal asymmetry hypothesis.
  • Limitations:: Review article; PPS-specific (surviving motor units); no direct evidence linking postural asymmetry to PPS fatigue vs neural mechanisms; published 2004.

11 Proessl et al. 2018 — Leg Strength Asymmetry NOT Associated with Fatigue in MS

  • Full Citation:: Proessl F, Ketelhut NB, Rudroff T. No association of leg strength asymmetry with walking ability, fatigability, and fatigue in multiple sclerosis. International Journal of Rehabilitation Research. 2018;41(1):81–86.
  • DOI:: https://doi.org/10.1097/MRR.0000000000000278
  • Key Findings::
    • n=15 MS patients: leg strength asymmetry did NOT correlate with walking ability, perceived fatigability, or fatigue severity
    • Suggests asymmetry alone is insufficient to produce fatigue – additional factors are required
    • MS fatigue likely driven by central (CNS) mechanisms rather than peripheral muscular asymmetry
  • Conclusion:: Null result that bounds the skeletal-asymmetry hypothesis: even in a neurological disease with established fatigue, muscular asymmetry does not predict fatigue severity. This suggests that if skeletal asymmetry contributes to ME/CFS fatigue, it must do so through mechanisms beyond simple muscular workload asymmetry (e.g., ANS irritation, systemic inflammatory response, or chronic metabolic perturbation).
  • Limitations:: Small sample (n=15); MS-specific (CNS demyelination dominates pathophysiology); leg strength asymmetry measured by dynamometer, not structural skeletal asymmetry (LLD, scoliosis); no metabolic or ANS outcomes.

12 Fava et al. 2026 — Sciatic Scoliosis Secondary to Lumbar Disc Herniation: Systematic Review

  • Full Citation:: Fava M, Mendola E, Perna F, Raimondini L, Giavaresi G, Toscano A. Clinical characteristics, surgical management and outcomes of sciatic scoliosis secondary to lumbar disc herniation: a systematic review. Life. 2026;16(4):589.
  • DOI:: https://doi.org/10.3390/life16040589
  • Key Findings::
    • Systematic review: 19 studies, 488 patients with sciatic scoliosis (acute antalgic spinal listing from disc herniation)
    • Sciatic scoliosis is a functional (not structural) deformity driven by pain-avoidance posture
    • Resolves with disc surgery in the majority of cases
    • Distinct from idiopathic/structural scoliosis – important for differential diagnosis
  • Conclusion:: Acute spinal deformity can be functional (pain-driven), not structural. Any hypothesis linking scoliosis to ME/CFS must distinguish between structural deformities (rotoscoliosis, DAMI) and functional listings (pain-avoidance, disc pathology). Most adult spinal asymmetries are mixed – functional listing can become structural over time.
  • Limitations:: Sciatic scoliosis is acute and reversible – minimal relevance to chronic structural asymmetry; no fatigue/ANS outcomes.

References

Cornelis, Justien, Kayleigh De Meulemeester, Wens Christiaens, Pascale Jonckheer, Isabelle Savoye, Marie Dauvrin, Laurence Kohn, and Diego Castanares-Zapatero. 2026a. “Management of Encephalomyelitis/Chronic Fatigue Syndrome in Belgium: An Analysis Based on Patient Needs – Supplement.” 420S. KCE Reports. Belgian Health Care Knowledge Centre (KCE). https://doi.org/10.57598/R420S.
———. 2026b. “Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Belgium: An Analysis Based on Patient Needs.” 420. KCE Reports. Belgian Health Care Knowledge Centre (KCE). https://doi.org/10.57598/R420C.