Proposed Diagnostic Criteria for ME/CFS
In 2015, the Institute of Medicine published diagnostic criteria for ME/CFS
In adults and children. The criteria state that three required symptoms and at least one of two additional symptoms are required for diagnosis.
A substantial reduction or impairment in the ability to engage in pre-illness levels of activity (occupational, educational, social, or personal life) that:
lasts for more than 6 months
is accompanied by fatigue that is:
often profound
of new onset (not life-long)
not the result of ongoing or unusual excessive exertion
not substantially alleviated by rest
Post-exertional malaise (PEM)*—worsening of symptoms after physical, mental, or emotional exertion that would not have caused a problem before the illness.
PEM often puts the patient in relapse which may last days, weeks, or even longer.
For some patients, sensory overload (light and sound) can induce PEM.
The symptoms typically get worse 12 to 48 hours after the activity or exposure and can last for days or even weeks.
Unrefreshing sleep—
Patients with ME/CFS may not feel better or less tired after a full night's sleep.
This may occur despite the absence of specific objective sleep alterations.
To be diagnosed with ME/CFS, patients must have at least one of the symptoms below. These are in addition to the three required symptoms above.
Cognitive impairment*—problems with thinking, memory, executive function, and information processing. They also have attention deficit and impaired psychomotor functions.
All can be exacerbated by exertion, effort, prolonged upright posture, stress, or time pressure.
This may have serious consequences on a patient's ability to maintain a job or attend school full time.
Orthostatic intolerance— a worsening of symptoms upon assuming and maintaining upright posture. This is measured by heart rate and blood pressure abnormalities during standing, bedside orthostatic vital signs, or head-up tilt testing.
Symptoms including lightheadedness, fainting, increased fatigue, cognitive worsening, headaches, or nausea are worsened while upright (either standing or sitting). Symptoms are improved (though not necessarily fully resolved) with lying down.
Orthostatic intolerance is often the most bothersome manifestation of ME/CFS among adolescents.
* The frequency and severity of these symptoms need to be evaluated. The IOM committee specified, for diagnosis, patients should have symptoms least half of the time with moderate, substantial, or severe intensity.
Exposure to infection leads to concomitant and persistent immune dysfunction and changes in the gut microbiome. Immune dysfunction affects both innate and adaptive immune systems that are sex-dependent. It is hypothesized that these changes are driven by antigen persistence of the infectious pathogen, These immune and microbial alterations impact the brain, leading to decreased concentrations of metabolites which impacts brain function. The catecholamine nuclei release lower levels of catechols, which impacts the autonomic nervous system and manifests with decreased heart rate variability and decreased baroreflex cardiovascular function, with downstream effects on cardiopulmonary capacity. Using functional brain imaging, researchers at NINDS also found that the temporoparietal junction was hypoactive during motor tasks in the ME/CFS group, It is not the kind of weakness that you see in patients with strokes—if the person is forced to do so, they can exert full strength. But the hypoactivity of the temporoparietal junction limits the brain from exerting that complete effort because too much effort, either cognitive or motor, wipes them out.
Supine and standing transcranial dopplers to assess for cerebral perfusion; complete autonomic reflex testing, including quantitative sudomotor axon reflex test; and a two-day cardiopulmonary test. These tests have shown significant difference between patients with ME/CFS and healthy controls in prior studies.
On March 12, RECOVER announced the opening of two phase 2 trials under the umbrella of RECOVER-AUTONOMIC, which will involve testing potential treatments in adults who have dysautonomia following COVID-19 infection.
Impairment in function with profound fatigue:
How fatigued are you?
What helps your fatigue the most (resting, lying down, quiet situations, not exercising or avoiding exercise)?
What makes the fatigue worse?
What are you able to do now?
How does it compare with what you were able to do before?
Think back to what you were able to do before you became sick.
How much has this illness affected: (a) your ability to work? (b) your ability to take care of yourself/your family and to do chores?
What happens when you try to push through the fatigue?
Post-exertional malaise:
What happens to you as you engage in normal physical or mental exertion? or after?
How much activity does it take you to feel ill?
What symptoms develop from standing or exertion?
How long does it take to recover from physical or mental effort?
If you go beyond your limits, what are the consequences?
What types of activities do you avoid because of what will happen if you do them
Unfrefreshing sleep:
Do you have any problems getting to sleep or staying asleep?
Do you feel rested in the morning or after you have slept?
Tell me about the quality of your sleep.
Do you need too much sleep?
Do you need to take more naps than other people? (There may be other sleep disruptors as well.)
Cognitive impairments:
Do you have problems doing the following activities: driving, watching a movie, reading a book/magazine, completing complex tasks under time constraints, following/participating in conversation, doing more than 1 thing at a time?
Compared with before your illness, how is your performance at work or school now?
Orthostatic intolerance:
How do you feel when you have been standing still for more than a few minutes?
What happens to you after you get up rapidly after lying down or sitting for a long time?
How long can you stand before feeling ill? For example, can you do the dishes? Can you stand in line for a bus or movie? Are you able to grocery shop or go to a mall?
How does hot weather affect you?
Do you study or work lying down, in bed or a recliner? Why?
Do you prefer to sit with knees to your chest or legs under you?
All questions should explore frequency and severity. To fulfill 2015 National Academy of Medicine diagnostic criteria, symptoms must be of at least moderate severity and present at least 50% of the time.
Clinicians should ask additional questions to understand the nature of fatigue; for instance, “What do you mean by fatigued?” and “On a scale of 0 (no energy) to 10 (full energy), how fatigued are you?”
Adapted from the National Academy of Medicine Report Guide for Clinicians, 97 with permission of the National Academy of Sciences.
CBC with diff, CMP, Rheumatoid factor, Four-point salivary cortisol (eg, wakening, at noon, 4:00 PM, and bedtime), AM cortisol, ANA, ENA, TSH, FT4, CRP, ESR, Vit D, ferritin, HIV, CK, acute hepatitis panel, lyme, TB, giardiasis, WNV, syphilis, EBV, parvovirus B19, coccidiomycosis, Celiac panel, 24-Urine heavy metal screen, mold, mycotoxins, lead, mercury, UA.
Rule out:
Sleep apnea, narcolepsy, periodic limb movement disorder
Systemic lupus erythematosus, rheumatoid arthritis, polymyositis, polymyalgia rheumatica
Cardiomyopathy, coronary artery disease, pulmonary hypertension, valvular heart disease, arrhythmias
Primary and secondary cancers
Multiple sclerosis, Parkinson disease, myasthenia gravis, vitamin B12 deficiency, cerebrospinal fluid leak, Chiari malformation, traumatic brain injury, spinal stenosis, craniocervical instability, seizures
Anxiety, depression,a bipolar affective disorder
Anemia (iron deficiency, other treatable forms), iron overload
Severe obesity (body mass index >40 kg/m2 ), overwork, athletic overtraining syndrome, asthma, chronic obstructive pulmonary disease
Postexertional malaise
Nonpharmacologic approaches to conserve energy and to minimize postexertional malaise
Pacing of physical and cognitive activity
Assistive devices, such as motorized scooters, handicap parking stickers, shower chairs to conserve energy
Home health aides for those who are more severely ill
Ear plugs, eye masks, perfume-free environments to decrease sensory stimulation; may need to maintain low sensory environment for the most severely ill.
School or work accommodations, such as flexible hours, shortened days.
Pharmacologic approaches: No specific recommendations
Orthostatic intolerance
Nonpharmacologic approaches
Salt and fluid loading, electrolyte drinks
Compression stockings
Positional changes; avoid prolonged sitting or standing
Consistent, tailored exercise as long as the patient can perform them without triggering postexertional malaise; may need to exercise lying down, seated, or in water
Treat comorbidities that may contribute to orthostatic intolerance
Pharmacologic approaches
Fludrocortisone, low-dose beta blockers, alpha-adrenergic agonists, pyridostigmine, desmopressin, ivabradine, Intravenous saline.
Sleep issues
Nonpharmacologic approaches
Sleep hygiene practices are a part of treatment but may be marginally effective in most patients; need to be tailored for severely ill and those with orthostatic intolerance
Meditation and relaxation exercises
Ear plugs and eye masks
Light therapy
Blue light filters
Pharmacologic therapies
Trazadone, low-dose tricyclic antidepressants (eg, amitriptyline, doxepin), mirtazapine, antiepileptics (eg, gabapentin, pregabalin), clonazepam, cyclobenzaprine, zolpidem, eszopiclone, tizanidine, suvorexant, topiramate, hydroxyzine, alpha blockers (eg, clonidine, guanfacine, prazosin), diphenhydramine.
Cognitive dysfunction and fatigue
Nonpharmacologic approaches
Cognitive pacing (eg, focus on only 1 task at a time, limit reading time)
Simple memory aids (eg, calendar reminder systems, notes)
Positional changes: perform cognitive functions lying down and stay hydrated if orthostatic intolerance is a problem
Pharmacologic approaches
Methylphenidate, modafinil, armodafinil, amantadine
Caffeine if well tolerated
Immune dysfunction
Nonpharmacologic approaches. No specific recommendations.
Pharmacologic approaches:
Intravenous immunoglobulin, subcutaneous gamma globulin, inosine pranobex, hydroxychloroquine.
Pain
Nonpharmacologic approaches:
Pacing to avoid flare-up of pain
Hot or cold packs as needed to relieve the specific source of pain
Physical therapy, massage, myofascial release, acupuncture, dry needling of trigger points
Chiropractic treatments
Meditation and relaxation
Neurofeedback techniques may be helpful
Pharmacologic approaches
Low-dose naltrexone, serotonin-norepinephrine reuptake inhibitor (eg, duloxetine, milnacipran), antiepileptics (gabapentin, pregabalin), muscle relaxants (eg, cyclobenzaprine, tizanidine, baclofen), medical marijuana, nonsteroidal anti-inflammatory drugs (eg, celecoxib, meloxicam), acetaminophen, amitriptyline, tramadol.
Gastrointestinal issues
Nonpharmacologic approaches
Healthy, varied diet low in processed food. Some patients may be able to minimize gastrointestinal symptoms by eliminating certain foods (eg, 1 or more of caffeine, alcohol, spicy foods, aspartame, sugar, possibly dairy or gluten).
Pharmacologic approaches: If small intestinal bacterial overgrowth: rifaximin, oral vancomycin, metronidazol.
Clinical Template
Chronic complains of dysesthesias with the acute onset and progression to involve whole-body and multi focally. She has symptoms suggestive of small fiber neuropathy; however exam does not correlate with the extent and distribution of her symptoms. She meets criteria for mild check encephalomyelitis/chronic fatigue syndrome. She reports substantial reduction or impairment in her ability to engage in pre illness levels of activity and it has been well over 6 months of symptom onset. It is accompanied by fatigue which is reportedly profound and not alleviated by rest. She has post exertional malaise. She reports exercise intolerance, sleep impairment, whether she has underlying sleep disorders, including sleep apnea, or poor sleep hygiene needs to be investigated further. Overall, her symptoms are out of proportion to findings of the examination. Although she has a risk factor for neuropathy being diabetes mellitus, her clinical exam does not demonstrate sensory dysfunction. She also reports some autonomic symptoms. It was possible that she may have small fiber neuropathy. I explained to her that SFN association with condition such as fibromyalgia, ME/CFS.
You do meet criteria for chronic fatigue syndrome. yalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling and complex illness.
People with ME/CFS are often not able to do their usual activities. At times, ME/CFS may confine them to bed. People with ME/CFS have overwhelming fatigue that is not improved by rest. ME/CFS may get worse after any activity, whether it’s physical or mental. This symptom is known as post-exertional malaise (PEM). Other symptoms can include problems with sleep, thinking and concentrating, pain, and dizziness. People with ME/CFS may not look ill. However,
People with ME/CFS are not able to function the same way they did before they became ill.
ME/CFS changes people’s ability to do daily tasks, like taking a shower or preparing a meal.
ME/CFS often makes it hard to keep a job, go to school, and take part in family and social life.
ME/CFS can last for years and sometimes leads to serious disability.
At least one in four ME/CFS patients is bed- or house-bound for long periods during their illness.
Scientists have not yet identified what causes myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). It is possible that ME/CFS has more than one cause, meaning that patients with ME/CFS could have illness resulting from different causes (see below). In addition, it is possible that two or more triggers might work together to cause the illness.
There is no cure or approved treatment for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, some symptoms can be treated or managed. Treating these symptoms might provide relief for some patients with ME/CFS but not others. Other strategies, like learning new ways to manage activity, can also be helpful.
Patients, their families, and healthcare providers need to work together to decide which symptom causes the most problems. This should be treated first. Patients, families, and healthcare providers should discuss the possible benefits and harms of any treatment plans, including medicines and other therapies.
Healthcare providers need to support their patients’ families as they come to understand how to live with this illness. Providers and families should remember that this process might be hard on people with ME/CFS.
For more information: https://www.cdc.gov/me-cfs
Chronic Fatigue Syndrome versus Systemic Exertion Intolerance Disease - PubMed