ME (Ramsay) and ME-International Case Criteria (ME-ICC): two distinct clinical entities

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. The review of the differences and similarities in the different case definitions for myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) by Lim and Son [1] deserves appreciation. Based on their analysis the authors acknowledge the “distinct view of ME and CFS” [2] and recognize four categories of case definitions: ME, ME/CFS, CFS [3] and Systemic Exertion Intolerance Disorder (SEID) [4]. Indeed these labels reflect very different case definitions [5]. According to Lim and Son [1] the first category comprises two ‘ME’ case definitions: ME (Ramsay) [6] and ME according to the International Case Criteria (ME-ICC) [7]. However as can be deduced from Table 2 [1], ME [6] and ME-ICC [7] are two distinct clinical entities [8]. ME (Ramsay) [6] is a neuromuscular disease. The discriminative symptom of ME is muscle fatiguability/ prolonged muscle weakness following trivial exertion. Ramsay states [9]: “[I]n my opinion a diagnosis should not be made without it”. Muscle fatigability is accompanied by “neurological disturbance, especially of cognitive, autonomic and sensory functions” [6]. So, in essence the case definition of ME (Ramsay) [6] is very simple [10] and requires two (types of ) symptoms: muscle fatigability/post-exertional muscle weakness and specific neurological symptoms. “Other characteristics include [..] a prolonged relapsing course and variation in intensity of symptoms within and between episodes, tending to chronicity.” [6]. In contrast, the ME-ICC case definition [7] is much more complex. The diagnosis ME-ICC requires postexertional neuro-immune exhaustion (mandatory symptom), at least three symptoms related to neurological impairments; at least three symptoms related to immune, gastro-intestinal, and genitourinary impairments; and at least one symptom related to energy production or transportation impairments [7]. The case criteria of ME [6] and ME-ICC [7] define two very different patient groups. Muscle fatigability/longlasting post-exertional muscle weakness, a hallmark feature of ME, is not required to be qualified as ME-ICC [7] patient. Symptoms indicating autonomic, sensory, and/or cognitive dysfunction, also mandatory for the diagnosis ME [6], are not required to meet the ME-ICC [7] ‘neurological impairments’ criterion. The diagnosis ME [6] requires only two type of symptoms (muscle fatigability/ post-exertional muscle weakness and “neurological disturbance”), but the polythetic definition of ME-ICC [7] requires a patient to have at least 8 symptoms. In essence, the case criteria of ME (Ramsay) and ME-ICC are not interchangeable (Fig. 1) [8]. Finally, it is important to note that, in contrast with Table 2 [1], ME [6] is often but not always triggered by an infection and that ME requires at least four symptoms: muscle fatigability/prolonged post-exertional muscle weakness and three neurological symptoms indicative of cognitive, autonomic and sensory dysfunction. In conclusion, ME (Ramsay) [6], a neuromuscular disease, is not comparable to ME-ICC [7]. ME [6], ME-ICC [7], ME/CFS, CFS [3] and SEID [4] are distinct clinical Open Access Journal of Translational Medicine

The review of the differences and similarities in the different case definitions for myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) by Lim and Son [1] deserves appreciation. Based on their analysis the authors acknowledge the "distinct view of ME and CFS" [2] and recognize four categories of case definitions: ME, ME/CFS, CFS [3] and Systemic Exertion Intolerance Disorder (SEID) [4].
Indeed these labels reflect very different case definitions [5]. According to Lim and Son [1] the first category comprises two 'ME' case definitions: ME (Ramsay) [6] and ME according to the International Case Criteria (ME-ICC) [7]. However as can be deduced from Table 2 [1], ME [6] and ME-ICC [7] are two distinct clinical entities [8]. ME (Ramsay) [6] is a neuromuscular disease. The discriminative symptom of ME is muscle fatiguability/ prolonged muscle weakness following trivial exertion. Ramsay states [9]: "[I]n my opinion a diagnosis should not be made without it". Muscle fatigability is accompanied by "neurological disturbance, especially of cognitive, autonomic and sensory functions" [6]. So, in essence the case definition of ME (Ramsay) [6] is very simple [10] and requires two (types of ) symptoms: muscle fatigability/post-exertional muscle weakness and specific neurological symptoms. "Other characteristics include [..] a prolonged relapsing course and variation in intensity of symptoms within and between episodes, tending to chronicity. " [6].
In contrast, the ME-ICC case definition [7] is much more complex. The diagnosis ME-ICC requires postexertional neuro-immune exhaustion (mandatory symptom), at least three symptoms related to neurological impairments; at least three symptoms related to immune, gastro-intestinal, and genitourinary impairments; and at least one symptom related to energy production or transportation impairments [7].
The case criteria of ME [6] and ME-ICC [7] define two very different patient groups. Muscle fatigability/longlasting post-exertional muscle weakness, a hallmark feature of ME, is not required to be qualified as ME-ICC [7] patient. Symptoms indicating autonomic, sensory, and/or cognitive dysfunction, also mandatory for the diagnosis ME [6], are not required to meet the ME-ICC [7] 'neurological impairments' criterion. The diagnosis ME [6] requires only two type of symptoms (muscle fatigability/ post-exertional muscle weakness and "neurological disturbance"), but the polythetic definition of ME-ICC [7] requires a patient to have at least 8 symptoms. In essence, the case criteria of ME (Ramsay) and ME-ICC are not interchangeable (Fig. 1) [8].
Finally, it is important to note that, in contrast with Table 2 [1], ME [6] is often but not always triggered by an infection and that ME requires at least four symptoms: muscle fatigability/prolonged post-exertional muscle weakness and three neurological symptoms indicative of cognitive, autonomic and sensory dysfunction.
Abbreviations ME: Myalgic encephalomyelitis; CFS: Chronic fatigue syndrome; SEID: Systemic Exertion Intolerance Disorder; ME-ICC: ME as defined by the International Case Criteria.