Abstract:
Orthostatic intolerance (OI) is characterized by the inability to maintain an upright posture without experiencing severe signs and symptoms, including hypotension, palpitations, light-headedness, pallor, fatigue, weakness, dizziness, impaired concentration, tremulousness, and nausea. The majority of patients with myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) exhibit OI, which is the primary factor restricting daily functional capacity.
During an upright posture, approximately 800 mL of blood is translocated from the intrathoracic venous compartment to the veins of the buttocks, pelvis, and legs. Under normal conditions, compensatory cardiovascular responses to this orthostatic stress include activation of the muscle pump through calf muscle contraction and a neurogenically mediated increase in heart rate and in systemic vascular resistance. The majority of the symptoms of OI are believed to be cardiovascular and related to reduced cerebral blood flow and excessive activation of the sympathetic nervous system.
However, compensatory sympathetic activation is essential for maintaining orthostasis. Many patients have a small left ventricle and associated low cardiac output. In addition, both the renin-aldosterone and antidiuretic hormone systems that regulate circulatory blood volume were downregulated.
Postural stability is necessary for maintaining the static balance critical for performing many daily activities. Recently studies have reported that postural instability or disequilibrium, potentially associated with central vestibular dysfunction, should be considered to be involved in the pathogenesis of OI among patients with ME/CFS. Disequilibrium should be recognized as an important cause of OI in those patients.
Source: Miwa K. Orthostatic intolerance with small heart and/or disequilibrium in patients with myalgic encephalomyelitis/chronic fatigue syndrome: clinical update and paradigm shift. Front Med (Lausanne). 2026 Jul 29;13:1744154. doi: 10.3389/fmed.2026.1744154. PMID: 42591853; PMCID: PMC13463185. https://pmc.ncbi.nlm.nih.gov/articles/PMC13463185/ (Full text)