Finding sub-groups in ME/CFS
Prof Leonard Jason worked with Dutch researchers to identify sub-groups of ME/CFS patients by symptom clusters. They used Leonard’s DePaul Symptom Questionnaire and data analysis software SOM. 45 subgroups were identified, some small. The researchers admit there are limitations with the study but have shown that sub-typing is possible.
“Classification of ME/CFS patients according to severity and symptoms patterns might be useful to develop tailored treatment options. Future studies are needed to investigate the relation between the identified symptom clusters and clinically relevant outcomes in patients with ME/CFS, including health-related quality of life and daily functioning.”
Table 2
DSQ-2 symptoms
| Dutch database (n = 337) | US database (n = 252) | |||
|---|---|---|---|---|
| Composite score Mean (SD) | Participants at 2/2 threshold (%) | Composite score Mean (SD) | Participants at 2/2 threshold (%) | |
| Fatigue/extreme tiredness | 75.4 (17.5) | 90.7 | 81.4 (15.1) | 98.4 |
| Post-exertional malaise | ||||
| Dead, heavy feeling after starting exercise | 50.1 (26.9) | 58.3 | 76.2 (24.7) | 87.7 |
| Next-day soreness or fatigue after everyday activities | 66.6 (20.8) | 80.7 | 75.3 (21.6) | 90.9 |
| Mentally tired after the slightest effort | 61.7 (23.7) | 72.8 | 68.2 (23.0) | 86.1 |
| Physically tired after minimum exercise | 67.0 (21.7) | 81.2 | 77.8 (20.6) | 92.9 |
| Physically drained or sick after mild activity | 59.8 (22.8) | 70.3 | 73.2 (22.5) | 88.9 |
| Muscle fatigue after mild physical activity | 63.1 (25.7) | 74.4 | 72.2 (26.1) | 86.1 |
| Worsening of symptoms after mild physical activity | 67.7 (23.7) | 78.5 | 78.8 (21.9) | 92.9 |
| Worsening of symptoms after mild mental activity | 59.1 (25.9) | 66.5 | 63.4 (27.0) | 76.6 |
| Difficulty reading (dyslexia) after mild physical or mental activity | 41.2 (30.8) | 40.6 | 44.6 (33.4) | 49.2 |
| Sleep | ||||
| Unrefreshing sleep | 73.9 (22.3) | 88.0 | 81.7 (19.1) | 94.8 |
| Need to nap daily | 56.2 (32.3) | 56.4 | 58.1 (30.0) | 66.7 |
| Problems falling asleep | 47.4 (28.0) | 49.9 | 55.9 (29.3) | 63.9 |
| Problems staying asleep | 52.7 (28.6) | 56.4 | 58.4 (30.5) | 65.1 |
| Waking up early in the morning (e.g. 3 AM) | 43.2 (28.3) | 43.1 | 48.9 (30.2) | 49.6 |
| Sleeping all day and staying awake all night | 18.4 (22.8) | 9.5 | 17.7 (27.2) | 16.3 |
| Daytime drowsiness | 52.6 (26.9) | 55.3 | 63.2 (26.9) | 77.0 |
| Pain | ||||
| Pain or aching in muscles | 59.6 (24.8) | 70.0 | 67.8 (26.0) | 80.2 |
| Joint pain | 51.1 (29.9) | 59.4 | 57.2 (32.9) | 64.7 |
| Eye pain | 31.2 (24.6) | 24.8 | 31.8 (28.8) | 31.0 |
| Chest pain | 23.1 (21.8) | 11.7 | 25.8 (25.7) | 19.0 |
| Bloating | 38.2 (25.8) | 37.6 | 47.1 (28.1) | 50.4 |
| Abdomen/stomach pain | 36.4 (23.2) | 30.8 | 42.1 (27.7) | 43.7 |
| Headaches | 24.8 (23.8) | 42.8 | 50.5 (26.3) | 55.2 |
| Aching of the eyes or behind the eyes | 29.0 (24.6) | 17.4 | 36.8 (29.8) | 36.9 |
| Sensitivity to pain | 27.0 (30.0) | 24.0 | 51.3 (32.9) | 59.5 |
| Myofascial pain | 15.7 (25.7) | 12.5 | 26.3 (34.0) | 30.2 |
| Neurocognitive | ||||
| Muscle twitches | 26.9 (22.3) | 16.6 | 34.4 (25.5) | 29.8 |
| Muscle weakness | 44.7 (27.4) | 45.2 | 63.5 (27.2) | 74.6 |
| Sensitivity to noise | 54.7 (26.8) | 57.8 | 61.0 (26.8) | 69.8 |
| Sensitivity to bright lights | 47.3 (28.4) | 46.0 | 53.2 (29.0) | 55.6 |
| Problems remembering things | 52.2 (22.5) | 58.0 | 67.9 (24.1) | 84.5 |
| Difficulty paying attention for a long period of time | 60.8 (24.0) | 73.3 | 70.4 (24.3) | 86.1 |
| Difficulty finding the right word to say, or expressing thoughts | 48.5 (22.4) | 50.7 | 61.1 (24.7) | 75.4 |
| Difficulty understanding things | 33.3 (21.5) | 23.2 | 48.5 (25.1) | 55.2 |
| Only able to focus on one thing at a time | 57.1 (25.2) | 67.6 | 64.9 (25.1) | 78.6 |
| Unable to focus vision | 21.5 (23.6) | 13.6 | 35.1 (27.4) | 31.7 |
| Unable to focus attention | 34.6 (22.9) | 27.2 | 50.9 (25.1) | 63.1 |
| Loss of depth perception | 18.5 (25.6) | 11.7 | 24.0 (29.5) | 21.4 |
| Slowness of thought | 47.3 (26.4) | 50.7 | 56.9 (25.5) | 71.4 |
| Absent-mindedness or forgetfulness | 44.0 (22.6) | 43.3 | 60.7 (24.5) | 78.6 |
| Feeling disoriented | 20.2 (22.7) | 11.2 | 35.9 (25.3) | 29.4 |
| Slowed speech | 21.3 (22.7) | 12.0 | 32.6 (27.1) | 31.3 |
| Poor coordination | 30.0 (25.1) | 21.3 | 46.2 (28.6) | 52.8 |
| Autonomic | ||||
| Bladder problems | 22.1 (28.0) | 18.3 | 35.6 (32.5) | 34.5 |
| Urinary urgency | 34.5 (27.6) | 31.3 | 39.7 (31.2) | 42.9 |
| Waking up at night to urinate | 51.2 (29.2) | 49.6 | 45.7 (32.0) | 46.4 |
| Irritable bowel problems | 39.8 (29.7) | 42.2 | 49.1 (32.7) | 55.6 |
| Nausea | 28.4 (21.5) | 16.6 | 33.8 (26.9) | 30.6 |
| Feeling unsteady on feet | 34.2 (24.1) | 23.7 | 44.0 (28.8) | 46.4 |
| Shortness of breath or trouble catching breath | 27.9 (22.2) | 17.7 | 39.8 (28.0) | 37.7 |
| Dizziness or fainting | 31.3 (22.2) | 19.6 | 42.1 (27.6) | 43.7 |
| Irregular heart beats | 27.8 (23.0) | 16.1 | 30.4 (26.8) | 28.6 |
| Heart beats quickly after standing | 31.3 (28.9) | 27.0 | 43.8 (32.6) | 46.0 |
| Blurred or tunnel vision after standing | 21.9 (26.4) | 16.6 | 30.5 (31.2) | 29.0 |
| Graying or blacking out after standing | 32.5 (24.2) | 23.2 | 22.7 (28.1) | 17.5 |
| Inability to tolerate an upright position | 27.3 (27.9) | 18.3 | 46.7 (34.3) | 52.0 |
| Neuroendocrine | ||||
| Losing weight without trying | 7.1 (16.7) | 4.1 | 13.2 (21.9) | 7.5 |
| Gaining weight without trying | 18.3 (25.8) | 13.9 | 36.3 (36.6) | 41.3 |
| Lack of appetite | 19.3 (21.4) | 11.4 | 30.3 (25.8) | 25.4 |
| Sweating hands | 12.9 (21.2) | 8.2 | 16.6 (25.7) | 13.1 |
| Night sweats | 33.0 (27.3) | 29.2 | 36.1 (30.5) | 31.3 |
| Cold limbs | 51.9 (26.4) | 58.3 | 46.9 (29.9) | 48.4 |
| Feeling chills or shivers | 31.7 (23.1) | 21.5 | 34.0 (26.3) | 32.9 |
| Feeling hot or cold for no reason | 42.4 (24.8) | 38.7 | 51.7 (26.9) | 61.1 |
| Felling like you have a high temperature | 29.6 (22.6) | 19.3 | 33.0 (27.2) | 29.4 |
| Feeling like you have a low temperature | 20.7 (25.5) | 15.8 | 24.7 (26.7) | 21.8 |
| Alcohol intolerance | 15.1 (30.8) | 14.2 | 40.1 (36.9) | 34.1 |
| Intolerance to extremes of temperature | 42.3 (35.0) | 41.7 | 64.9 (31.1) | 72.2 |
| Fluctuations in temperature throughout the day | 30.3 (28.5) | 26.4 | 45.2 (31.8) | 48.0 |
| Immune | ||||
| Sore throat | 30.1 (20.4) | 17.4 | 37.3 (25.7) | 32.9 |
| Tender/sore lymph nodes | 23.4 (22.9) | 14.4 | 37.5 (30.5) | 36.5 |
| Fever | 9.2 (16.9) | 1.6 | 16.1 (22.1) | 9.9 |
| Flu-like symptoms | 36.1 (23.7) | 28.3 | 51.8 (27.3) | 57.1 |
| Sensitivity to smells, food, medications, or chemicals | 25.6 (27.1) | 19.1 | 45.0 (32.7) | 46.8 |
| Viral infections with prolonged recovery periods | 16.9 (24.7) | 9.5 | 35.0 (32.7) | 32.5 |
| Sinus infections | 15.2 (24.0) | 10.4 | 21.9 (26.2) | 19.4 |
| Others | ||||
| Sensitivity to mold | 18.3 (28.9) | 16.6 | 27.2 (36.3) | 30.6 |
| Sensitivity to vibration | 22.9 (29.9) | 18.3 | 30.6 (35.0) | 32.9 |
Symptom-based clusters in people with ME/CFS: an illustration of clinical variety in a cross-sectional cohort, by Anouk W Vaes, Maarten Van Herck, Qichen Deng, Jeannet M Delbressine, Leonard A Jason, Martijn A Spruit in J Transl Med. 2023 Feb 10;21(1):112 [doi: 10.1186/s12967-023-03946-6]
Research abstract
Background:
Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a complex, heterogenous disease. It has been suggested that subgroups of people with ME/CFS exist, displaying a specific cluster of symptoms. Investigating symptom-based clusters may provide a better understanding of ME/CFS. Therefore, this study aimed to identify clusters in people with ME/CFS based on the frequency and severity of symptoms.
Methods:
Members of the Dutch ME/CFS Foundation completed an online version of the DePaul Symptom Questionnaire version 2. Self-organizing maps (SOM) were used to generate symptom-based clusters using severity and frequency scores of the 79 measured symptoms. An extra dataset (n = 252) was used to assess the reproducibility of the symptom-based clusters.
Results:
Data of 337 participants were analyzed (82% female; median (IQR) age: 55 (44-63) years). 45 clusters were identified, of which 13 clusters included ≥ 10 patients. Fatigue and PEM were reported across all of the symptom-based clusters, but the clusters were defined by a distinct pattern of symptom severity and frequency, as well as differences in clinical characteristics. 11% of the patients could not be classified into one of the 13 largest clusters. Applying the trained SOM to validation sample, resulted in a similar symptom pattern compared the Dutch dataset.
Conclusion:
This study demonstrated that in ME/CFS there are subgroups of patients displaying a similar pattern of symptoms. These symptom-based clusters were confirmed in an independent ME/CFS sample. Classification of ME/CFS patients according to severity and symptom patterns might be useful to develop tailored treatment options.