Friday 6 May 2022

Diagnosis of Myalgic Encephalomyelitis (ME) Part 1 - Tools for Diagnosis

Diagnosis Part 1

Myalgic Encephalomyelitis (ME) is a distinct, recognisable disease entity that is not difficult to diagnose and can in fact be diagnosed relatively early in the course of the disease, providing that the doctor has some experience with ME.

As with a wide variety of illnesses; lupus and multiple sclerosis (MS), for example, there is as yet no single test which can diagnose ME.

Therefore, ME must instead be diagnosed by a combination of: taking a detailed medical history to rule out other possible causes of symptoms, noting the type and severity of symptoms and other characteristics of the illness, the type of onset of the symptoms, acute or sudden onset of symptoms is seen in ME though feedback tells us that others experience gradual onset.

ME can be diagnosed within just a few consultations, if the doctor has some experience with ME.

The presence or absence of ‘fatigue’ is largely irrelevant in determining an ME diagnosis.

An accurate diagnosis can be made by a doctor using diagnostic criteria specifically written for and about ME such as the International Consensus Primer (ICP) 2012.

ME isn’t difficult to diagnose, unfortunately we have a healthcare system in Ireland which doesn’t know much about ME so it can take a long time to get a diagnosis.

Getting an accurate ME diagnosis requires proper understanding of ME and is based on a detailed clinical history, physical examination, and some laboratory investigations

Of course the common story is that once a diagnosis happens there are no Irish guidelines/policies to management and treatment which means a GP/Consultant can give you a diagnosis but may not have the information to follow up and advise you re management and treatment.

However, there is advice available re management and treatments, the best information comes from the expert patient community, and more formal information from the ICC and ICP as well as patient organisations and support groups.

Image by MEAI

Essential Steps & Resources for

Making a Diagnosis of

Myalgic Encephalomyelitis - M.E.

Questionnaires & Tools to Assess ME Symptoms & Severity

While symptoms vary from patient to patient there are a few resources available to aid a proper understanding and to confirm a diagnosis, documents that can be used to highlight individual symptoms and disability. There are many general self-report tools available online but we feel that the ones we suggest below are the best available. These include

· The best international criteria documents currently available Myalgic Encephalomyelitis International Consensus Criteria and Primer (ICC & ICP)

· Symptom & Severity, PEM & Paediatric questionnaires based on research (DePaul University)

· Bells Disability Scale

International Criteria

For diagnosis and management use the International Consensus Criteria, ICC-ME 2011 & the International Consensus Primer, ICP-ME 2012, both specifically written about and for ME, designed to assess the unique combination of symptoms found in ME. The Primer is written with doctors and other healthcare providers in mind.
Links to those below: -

The Myalgic Encephalomyelitis (ME) International Consensus Criteria (ICC)

The ICC 2011 is a medical case definition that can accurately diagnose myalgic encephalomyelitis (ME). As per the ICC, for pediatric and adult cases a diagnosis should be made immediately; there is no need to wait up to 6 months.

The International Consensus Criteria identify the unique and distinctive characteristic patterns of symptom clusters of ME. The broad spectrum of symptoms alerts medical practitioners to areas of pathology and may identify critical symptoms more accurately. Operational notes following each criterion provide guidance in symptom expression and contextual interpretation. ICC 2011

Myalgic encephalomyelitis is an acquired neurological disease with complex global dysfunctions. Pathological dysregulation of the nervous, immune and endocrine systems, with impaired cellular energy metabolism and ion transport are prominent features.
Although signs and symptoms are dynamically interactive and causally connected, the criteria are grouped by regions of pathophysiology to provide general focus.

How is ME Diagnosed
The symptoms of ME are numerous and can include but are not limited to the following:

A patient will meet the criteria for postexertional neuroimmune exhaustion (A), at least one symptom from three neurological impairment categories (B), at least one symptom from three immune/gastro-intestinal/genitourinary impairment categories (C), and at least one symptom from energy metabolism/transport impairments (D).

A. Postexertional neuroimmune exhaustion (PENE pen’-e): Compulsory

This cardinal feature is a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions. Characteristics are as follows:

1. Marked, rapid physical and/or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.

2. Postexertional symptom exacerbation:e.g.acute flu-like symptoms, pain and worsening of other symptoms.

3. Postexertional exhaustion may occur immediately after activity or be delayed by hours or days.

4. Recovery period is prolonged, usually taking 24h or longer. A relapse can last days, weeks or longer.

5. Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.

B. Neurological impairments

At least one symptom from three of the following four symptom categories

1. Neurocognitive impairments

a. Difficulty processing information: slowed thought, impaired concentration e.g. confusion, disorientation, cognitive overload, difficulty with making decisions, slowed speech, acquired or exertional dyslexia

b. Short-term memory loss:e.g. difficulty remembering what one wanted to say, what one was saying, retrieving words, recalling information, poor working memory

2. Pain

a. Headaches:e.g. chronic, generalized headaches often involve aching of the eyes, behind the eyes or back of the head that may be associated with cervical muscle tension; migraine; tension headaches

b. Significant pain can be experienced in muscles, muscle-tendon junctions, joints, abdomen or chest. It is noninflammatory in nature and often migrates. e.g. generalized hyperalgesia, widespread pain (may meet fibromyalgia criteria), myofascial or radiating pain

3. Sleep disturbance

a. Disturbed sleep patterns:e.g. insomnia, prolonged sleep including naps, sleeping most of the day and being awake most of the night, frequent awakenings, awaking much earlier than before illness onset, vivid dreams/nightmares

b. Unrefreshed sleep:e.g. awaken feeling exhausted regardless of duration of sleep, day-time sleepiness

4. Neurosensory, perceptual and motor disturbances

a. Neurosensory and perceptual:e.g. inability to focus vision, sensitivity to light, noise, vibration, odour, taste and touch; impaired depth perception

b. Motor:e.g. muscle weakness, twitching, poor coordination, feeling unsteady on feet, ataxia

C. Immune, gastro-intestinal and genitourinary Impairments

At least one symptom from three of the following five symptom categories

1. Flu-like symptoms may be recurrent or chronic and typically activate or worsen with exertion.e.g. sore throat, sinusitis, cervical and/or axillary lymph nodes may enlarge or be tender on palpitation

2. Susceptibility to viral infections with prolonged recovery periods

3. Gastro-intestinal tract:e.g. nausea, abdominal pain, bloating, irritable bowel syndrome

4. Genitourinary: e.g. urinary urgency or frequency, nocturia

5. Sensitivities to food, medications, odours or chemicals

D. Energy production/transportation impairments: At least one symptom

1. Cardiovascular:e.g. inability to tolerate an upright position - orthostatic intolerance, neurally mediated hypotension, postural orthostatic tachycardia syndrome, palpitations with or without cardiac arrhythmias, light-headedness/dizziness

2. Respiratory:e.g. air hunger, laboured breathing, fatigue of chest wall muscles

3. Loss of thermostatic stability:e.g. subnormal body temperature, marked diurnal fluctuations; sweating episodes, recurrent feelings of feverishness with or without low grade fever, cold extremities

4. Intolerance of extremes of temperature

Paediatric considerations

Symptoms may progress more slowly in children than in teenagers or adults. In addition to postexertional neuroimmune exhaustion, the most prominent symptoms tend to be neurological: headaches, cognitive impairments, and sleep disturbances.

1. Headaches: Severe or chronic headaches are often debilitating. Migraine may be accompanied by a rapid drop in temperature, shaking, vomiting, diarrhoea and severe weakness.

2. Neurocognitive impairments: Difficulty focusing eyes and reading are common. Children may become dyslexic, which may only be evident when fatigued. Slow processing of information makes it difficult to follow auditory instructions or take notes. All cognitive impairments worsen with physical or mental exertion. Young people will not be able to maintain a full school programme.

3. Pain may seem erratic and migrate quickly. Joint hypermobility is common.

Notes: Fluctuation and severity hierarchy of numerous prominent symptoms tend to vary more rapidly and dramatically than in adults.

[Severe ME considerations
Severe ME, which includes those with severe, very severe and profound ME, sees patients suffering from a horrendous, disabling form of Myalgic Encephalomyelitis. These patients are isolated/confined to bed due to the severity of their symptoms and disabilities, and are often unable to leave their home even to seek medical care.]

Myalgic Encephalomyelitis: International Consensus Criteria 2011

The Myalgic Encephalomyelitis (ME) International Consensus Primer (ICP)

The ICP 2012 is a physician guide that includes immune dysfunction, neurological issues, and cardiac abnormalities that are often overlooked in other information. The ICC alone is not enough to make an ME diagnosis, the next step is to confirm the ME diagnosis. The International Consensus Primer guides doctors to diagnose, treat and rule out other diseases. It is a booklet prepared by ME experts to guide doctors in treating those who fit the ICC. ICP 2012

Symptom Questionnaire (DePaul Symptom Questionnaire DSQ)

The DePaul Symptom Questionnaire (DSQ-2) is a self-report assessment created by Leonard Jason at DePaul University, Chicago, Illinois, US. With 54 questions in total, the DSQ Symptom Questionnaire assesses key symptoms of ME such as post-exertional malaise, sleep, pain, neurological/cognitive impairments and autonomic, neuroendocrine and immune symptoms. At each item, participants have to rate the frequency and severity of the symptom on a scale from 0 to 4. You can put a score for how frequently you have each symptom and how severe it is. The questionnaire is based on research so useful to print out to complete and shown to your GP/Consultant/other.

As much as anything the questionnaire can teach your GP what ME is and you might realise things you think aren’t ME actually are!

This is the link to the DSQ-2 symptom questionnaire.

PEM Questionnaire (De Paul DSQ PEM Questionnaire - DPEMQ)

Post Exertional Neuroimmune Exhaustion (PENE) is a key symptom of Myalgic Encephalomyelitis (ME). PENE is referred to as PEM by others. The PEM questionnaire by De Paul is a questionnaire on the post exertional response, i.e., PEM (PENE as per the ICC), an essential criterion for an ME diagnosis. See more on PENE (PEM) further on in this guide.

By answering the questions, you get an idea of how ‘activity’, anything you do physically, cognitively, emotionally, affects you and what your individual post exertional response is, i.e., what symptoms occur and increase. Every person with ME is different. The post exertional response for a lot of people might not occur straight away and tends to be delayed 24 hours or 48 hours after activity. The questionnaire includes key indicators that show within answering a set of questions that it sounds like ME.

This is the link to the De Paul Post Exertional Questionnaire.

Paediatric Questionnaires

The DSQ- PED questionnaires from De Paul consists of a parent form and a child form. Parents can fill in a symptom questionnaire to evidence the child's symptoms and severities to present to the child’s medic. Medics can receive data about the child with ME from both child and their parents to obtain a thorough understanding of the child's ME. Children under the age of 12, or those with reading or comprehension difficulties, complete this questionnaire with the assistance of a parent or guardian.

These forms are based on research by De Paul.

DSQ-Ped Parent Form here

DSQ-Ped Child Form here

Full access to all the DePaul questionnaires

All the De Paul adult & paediatric questionnaires in different languages here

Bells Disability Scale

We tend to refer to the different severities of ME as Mild, Moderate, Severe, Very Severe, Profound - we refer to those as general categories which really have ranges within themselves ie Mild has its own range, as does Moderate and so on.
A good scale that could be used along with these categories to determine near exact range is the Bells Disability Scale for example, see below. Different people suffer in different ways but the scale gives an idea of the level of disability.

• It can be used by both Patient and Doctor to monitor progress/relapses of ME over time.

• Tick which descriptor best describes you today.

Bells Disability Scale

% Description

100 No symptoms at rest; no symptoms with exercise; normal overall activity level; able to work fulltime without difficulty.

90 No symptoms at rest; mild symptoms with activity; normal overall activity level; able to work full-time without difficulty.

80 Mild symptoms at rest; symptoms worsened by exertion; minimal activity restriction noted for activities requiring exertion only; able to work full-time with difficulty in jobs requiring exertion.

70 Mild symptoms at rest; some daily activity limitation clearly noted; overall functioning close to 90% of expected except for activities requiring exertion; able to work full-time with difficulty.

60 Mild to moderate symptoms at rest; daily activity limitation clearly noted; overall functioning 70% - 90%; unable to work full-time in jobs requiring physical labour, but able to work full-time in light activities if hours flexible.

50 Moderate symptoms at rest; moderate to severe symptoms with exercise or activity; overall activity level reduced to 70% of expected; unable to perform strenuous duties, but able to perform light duty or desk work 4-5 hours a day, but requires rest periods.

40 Moderate symptoms at rest; moderate to severe symptoms with exercise or activity; overall level reduced to 50% - 70% of expected; not confined to house; unable to perform strenuous duties; able to perform light duty or desk work 3-4 hours a day but requires rest periods.

30 Moderate to severe symptoms at rest; severe symptoms with any exercise; overall activity level reduced to 50% of expected; usually confined to house; unable to perform strenuous tasks; able to perform desk work 2-3 hours a day, but requires rest periods.

20 Moderate to severe symptoms at rest; severe symptoms with any exercise; overall activity level reduced to 30% - 50% of expected; unable to leave house except rarely; confined to bed most of day; unable to concentrate for more than 1 hour a day.

10 Severe symptoms at rest; bedridden the majority of the time; no travel outside of the house; marked cognitive symptoms preventing concentration.

0 Severe symptoms on a continuous basis; bedridden constantly; unable to care for self

Please see more about the Bells Disability Scale and the full Bells Disability scale here

Functional Ability

A functional ability scale is an important tool to help you work out where you are with your ME severity, we include the one from Action for ME (UK) here

Grip Test

Research has shown that grip strength is associated with a number of health indicators, including mobility. While grip strength isn't necessarily used when you're walking, it's associated with mobility. People with physical limitations are more likely to have decreased grip strength. A grip test is used as an objective measure of disease status and severity in ME, and correlates it with fatigue and pain severity and with physical and mental functioning.

'Hand grip strength (HGS) is a reliable measurement of localized muscle strength and reflects the force derived from the combined contraction of extrinsic hand muscles. Originally developed for hand surgery to determine capacity after trauma or surgery, hand grip strength correlates well with other muscle function tests such as knee extension strength. Moreover, reduced HGS has been associated with morbidity and mortality, with low values associated with falls, disability, impaired health-related quality of life and prolonged length of stay in hospital. It has also shown to be strongly correlated with post-operative complications and has been reported as a predictor of loss of functional status and short-term survival in hospitalized patients.' (from Hand Grip Strength as a Clinical Biomarker for ME/CFS and Disease Severity - PMC (nih.gov))

‌How to Measure Grip Strength:
Grip strength is measured using an instrument called a dynamometer. Measure your grip strength with a dynamometer using the following steps:‌

Hold your arm with your elbow bent at a 90-degree angle.
Squeeze the dynamometer as hard as possible.
Apply grip force in a smooth motion. Avoid jerking.
Repeat twice more for a total of three times.
Your grip strength is the average of the three readings.

Overall, patients with ME have significant lower hand grip strength (HGS) values than healthy controls (HC). MS is the most common immune-mediated inflammatory demyelinating disease of the central nervous system. One of the most prominent features of MS is motor weakness. Therefore, it is expected people with MS to display lower HGS.

However, ME patients also have significantly lower HGS values compared to HC, even after controlling for age, sex, and BMI, with even mild cases showing lower HGS. People with ME are not malnourished and have preserved muscle tonus, suggesting that other than local factors related to the integrity of upper limb must be involved.

It has been suggested that these might relate to ongoing inflammation or disruption of signaling mechanisms between central nervous system and periphery, and it may also represent an overall measurement of “physical health and functioning.” More here

NASA Lean Test

An alternative to Tilt Table Testing is the NASA Lean Test

Note! Most people with ME especially those with more severe ME would not be able to do Tilt Table Testing. An alternative test for those who can get out of bed without difficulties, and who are able to sit up for 10 minutes and then also stand for at least 10 minutes is the NASA Lean Test (same as 'poor man's tilt table test). For those with more severe ME, doctors can monitor pulse and blood pressure while the patient is standing, and again while lying down. This may need to be repeated several times, and is known as the ‘poor man’s tilt table test, or more modernly as the NASA Lean Test.

Step By Step Procedure in the NASA Lean Test

Ask the patient to lie down and rest quietly for 15 - 20 minutes.

Then take the first blood pressure and pulse readings and make a note of them.

Ask the patient to sit up for 10 minutes, or as long as they can manage without severe problems, and then take another set of readings and make a note.

Then direct the patient to stand up for 10 minutes, leaning against a wall, but without fidgeting or moving or talking which can affect the result. Then take another set of readings and make a note.

After another 10 minutes of standing and leaning, take the readings again and make a note.

Keep leaning. Do not flex any muscles or talk.

After another ten minutes, take the readings again.

Important Notes for the doctor and patient with regards to the NASA Lean Test!

If at any time the patient starts to feel sweaty or hot or nauseous, the doctor/practitioner needs to take the patient's bp and pulse readings right away and get the patient lying down as soon as possible.

Many patients will not be able to tolerate this much time upright and will need to stop the test partway through. If this happens, take another reading (if possible) and then the patients lies down again.

Failure to stop the tests when the patient becomes severely ill can lead to a loss of consciousness, or severe relapse lasting days, weeks or even months in the very severely affected. Someone should always be standing near the patient to catch them if they fall and serious requests to stop the test must be acted on in a timely manner.

Assessing the readings taken:

For Neurally Mediated Hypotension* (NMH), the patient has to have a 20-25 mm drop in systolic blood pressure (the higher number).

If the patient's pulse suddenly rises at least 30 bpm (beats per minute), then it is likely they have Postural Orthostatic Tachycardia Syndrome* (POTS).

Dr. Rowe believes that they are both really the same thing - with either, if the patient doesn't lie down, they're going to pass out. And the treatment for both is the same.

*Neurally mediated hypotension is also known by the following names: the fainting reflex, neurocardiogenic syncope, vasodepressor syncope, the vaso-vagal reflex, and autonomic dysfunction. Hypotension is the formal medical term for low blood pressure, and syncope is the term for fainting. Neurally mediated hypotension occurs when there is an abnormal reflex interaction between the heart and the brain, both of which usually are structurally normal.

*Postural orthostatic tachycardia syndrome (or POTS) is a condition of orthostatic intolerance in which a change from the supine position to an upright position causes an abnormally large increase in heart rate, often, but not always accompanied by a fall in blood pressure. Patients with POTS also have problems in maintaining homeostasis when changing position ie moving from one chair to another or reaching above their heads.

Symptoms include an abnormally large increase in heart rate upon standing, lightheadedness, extreme fatigue, nausea, headache, chest pain, exercise intolerance and impaired concentration. Patients may exhibit mild hypotension while standing, but most do not experience fainting. POTS patients are usually significantly debilitated by their symptoms.

More Information on the NASA Lean Test

'A Simple Way to Assess Orthostatic Intolerance', an information document by Lucinda Bateman, includes images and pdf copies of instructions for medical providers and patients about how to do the NASA Lean Test, see here.

More Useful Resources for Diagnosis

Patient Doctor Check List Based on the ICC

Patient Doctor Check List Based on ME- International Consensus Criteria (ICC) from GAME - ICC, thanks to Wendy Boutillier here

Simple Tool to determine if the patient meets the ICC Criteria

An online questionnaire was developed by Schweizerische Gesellschaft für ME, a patient association in Switzerland, to help determine whether the diagnosis of ME according to the International Consensus Criteria (ICC) is applicable to a patient. This tool could be used as an easier/shorter alternative to the De Paul symptom and severity questionnaires by the doctor as well as the patient: ICC Questionnaire

Conditions to Rule Out Information Sheet (by ME International US)

Part of the process of confirming an ME diagnosis is to rule out other diseases. Too often patients discover after getting an ME label that a treatable illness had been overlooked. ME International's Conditions to Rule Out handout has useful patient information regarding how to help diagnose ME.

Films about various aspects of ME

Includes films about ME & Severe ME, from Dialogues for ME, by Natalie Bolton & Josh Biggs, produced with a Wellcome Public Engagement Fund Award

Dialogues for ME introduction to ME, link here: Introduction to ME

Reduced function and the range of symptoms in ME: Patients Accounts - Symptoms

Post exertional intolerance and the post exertional response, i.e. PENE, also referred to as PEM, the cardinal feature of ME: Understanding Post Exertional Malaise - a Hallmark Feature

A Brief Guide to Post Exertional Intolerance

About Myalgic Encephalomyelitis (ME)