Friday, 22 February 2019

Are surgeons missing the major differential diagnosis that is more common than multiple sclerosis and HIV combined?

Royal College Of Surgeons Blog

Are surgeons missing the major differential diagnosis that is more common than multiple sclerosis and HIV combined?

21 Feb 2019

Nina Muirhead

It’s a great feeling when we meet a new outpatient that we know how to manage surgically. Unfortunately, every surgical specialty experiences a subgroup of patients who present with symptoms that cannot be resolved by surgery. These symptoms may span immune, neurological and vascular systems within the body or brain and may manifest themselves in various ways in several organs at the same time. (See list of symptoms below)

Often these patients have been back-and-forth to the GP or passed on by other medical and surgical specialties. They tend to be the cases that are difficult to diagnose, quantify, understand and detect with routine investigations.

My story

In September 2016, I became ill with acute Epstein Barr Virus Glandular Fever. I continued working, exercising and trying to lead a normal family and social life. I developed all the symptoms listed below, as well as post-exertional malaise (PEM). Every time I tried to do anything challenging (mentally, physically or emotionally) I would experience severe symptom exacerbation and flu-like sore throats with head and neck pain. I couldn’t work, read or watch TV. I couldn’t look after myself, let alone my children, and could barely walk and digest food. Eventually I was diagnosed with Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS).

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome

Often triggered by a viral infection, ME/CFS, can be distinguished from medical and psychiatric conditions by the presence of debilitating fatigue for more than six months and/or combinations of cognitive dysfunction, total body pain, unrefreshing sleep that does not restore normal function and PEM.1

I was never taught about ME/CFS at medical school and it certainly wasn’t in the MRCS examinations that I passed a decade ago. I had a vague notion that it was an illness related to deconditioning, but I was wrong. ME/CFS is a serious neurological condition which can be fatal.

Given that my own prior understanding of ME/CFS was so misguided, I was not surprised to read in the BMJ that 90% of cases of ME/CFS are thought to go undiagnosed, suggesting that people with ME/CFS are substantially undercounted, underdiagnosed and undertreated.2 In another study, 41.9% of ME/CFS patients were told by emergency department staff that it was all in their heads.3 Biobank data suggests ME/CFS is a heritable condition estimated to affect over 286,000 people in the UK; this is more common than multiple sclerosis and HIV combined, and many patients are waiting years for a diagnosis.

Parliamentary proceedings

On the 24th January 2019, ME/CFS was debated for the first time in 20 years in the main chamber of the House of Commons. It was unanimously agreed that: the Government should provide increased funding for biomedical research into the diagnosis and treatment of ME; the suspension of Graded Exercise Therapy and Cognitive Behavioural Therapy as means of treatment should be supported; GP’s and medical professional’s training needed updating to ensure they are equipped with clear guidance on diagnosis of ME, as well as appropriate management advice to reflect international consensus on best practice and; the current trends of subjecting ME families to unjustified child protection procedures is concerning.4

Differential diagnosis

When you next see a patient with any of the symptoms listed below, ask them about PEM and consider ME/CFS as a differential diagnosis. While they may not leave your clinic with an operation booked, they may finally get a diagnosis, and the time spent in your clinic will have made a big difference to their lives.

Typical symptoms of ME/CFS

·         Post Exertional Malaise (PEM)
·         Irritable bowel
·         Non-specific abdominal pain
·         Urinary frequency or urgency
·         Tinnitus
·         Facial pain
·         Sore throat
·         Unrefreshing sleep
·         Postural tachycardia and/or orthostatic hypotension
·         Headaches
·         Dizziness
·         Nerve pain and tingling
·         Bone, muscle and joint pain
·         Generalised weakness
·         Poor circulation
·         Atypical chest pain
·         Dysmenorrhea
·         Fatigue
·         Sensitivity to light, temperature, sound and chemicals
·         Difficulty with memory, word finding and multitasking

Further reading



Thursday, 21 February 2019

Altered Erythrocyte Biophysical Properties in Chronic Fatigue Syndrome

Amit K. Saha   Brendan R. Schmidt   Julie Wilhelmy   Vy Nguyen   Justin K. Do   Vineeth C. Suja   Mohsen Nemat-Gorgani   Anand K. Ramasubramanian   Ronald W. Davis

Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a multi-systemic illness of unknown etiology affecting millions of individuals worldwide. In this work, we tested the hypothesis that erythrocyte biophysical properties are adversely affected in ME/CFS. We tested erythrocyte deformability using a high-throughput microfluidic device which mimics microcapillaries. We perfused erythrocytes from ME/CFS patients and from age and sex matched healthy controls (n=14 pairs of donors) through a high-throughput microfluidic platform (5μmx5μm). We recorded cell movement at high speed (4000 fps), followed by image analysis to assess the following parameters: entry time (time required by cells to completely enter the test channels), average transit velocity (velocity of cells inside the test channels) and elongation index (ratio of the major diameter before and after deformation in the test channel). We observed that erythrocytes from ME/CFS patients had higher entry time, lower average transit velocity and lower elongation index as compared to healthy controls. Taken together, this data shows that erythrocytes from ME/CFS patients have reduced deformability. To corroborate our findings, we measured the erythrocyte sedimentation rate for these donors which show that the erythrocytes from ME/CFS patients had lower sedimentation rates. To understand the basis for differences in deformability, we investigated changes in the fluidity of the membrane using pyrenedecanoic acid and observed that erythrocytes from ME/CFS patients have lower membrane fluidity. Zeta potential measurements showed that ME/CFS patients had lower net negative surface charge on the erythrocyte plasma membrane. Higher levels of reactive oxygen species in erythrocytes from ME/CFS patients were also observed. Using scanning electron microscopy, we also observed changes in erythrocyte morphology between ME/CFS patients and healthy controls. Finally, preliminary studies show that erythrocytes from “recovering” ME/CFS patients do not show such differences, suggesting a connection between erythrocyte deformability and disease severity.

Tuesday, 19 February 2019

Though I Have Afflicted Thee, I Will Afflict Thee No More 

C H Spurgeon's Cheque Book Of The Bank Of Faith Daily Devotional for 19th February 

Though I have afflicted thee, I will afflict thee no more.

Nahum 1:12

There is a limit to affliction. God sends it, and God removes it. Do you sigh and say, "When will the end be?" Remember that our griefs will surely and finally end when this poor earthly life is over, Let us quietly wait and patiently endure the will of the Lord till He cometh.

Meanwhile, our Father in heaven takes away the rod when His design in using it is fully served. When He has whipped away our folly, there will be no more strokes. Or, if the affliction is sent for testing us, that our graces may glorify God, it will end when the Lord has made us bear witness to His praise. We would not wish the affliction to depart till God has gotten out of us all the honor which we can possibly yield Him.

There may today be "a great calm." Who knows how soon those raging billows will give place to a sea of glass, and the sea birds sit on the gentle waves? After long tribulation the Rail is hung up, and the wheat rests in the garner. We may, before many hours are past, be just as happy as now we are sorrowful. It is not hard for the Lord to turn night into day. He that sends the clouds can as easily clear the skies. Let us be of good cheer. It is better on before. Let us sing hallelujah by anticipation.

Wednesday, 6 February 2019

No Faith? Our Struggle With Unbelief

By J.P. Thackway

“And He said unto them, why are ye so fearful? How is it that ye have no faith?” Mark 4:40

The first three gospels record the stilling of the storm on the lake of Galilee. It is one of the most powerful and impressive of the Lord’s miracles. This was especially so for Peter, Andrew, James, and John – fishermen – who well knew, when a storm arose, the terrors of those waters.

The freshwater lake of Galilee is 686 feet below sea level and less than 200 feet deep. It is bounded by high hills, from where cold winds can hit the warm surface of the water and whip up sudden squalls. Luke’s account shows this: “there came down a storm of wind on the lake” (Luke 8:23). Shallow water reacts to winds faster than deep water does, and hapless fisherman can be engulfed before they know it.

In Mark’s account we see how desperate their plight was, “And there arose a great storm of wind, and the waves beat into the ship, so that it was now full” (4:37). The next wave may have sunk the boat. The disciples felt completely at the mercy of the storm. We can spiritualise this, and apply it to our experience.

a] Storms of life do come.

Even to obedient disciples. Remember, they were obeying the Master in crossing the lake (Mark 4:35). We can be in the centre of God’s will and yet in the eye of a storm of trouble! Do not conclude that your maelstrom is because you have sinned. Of course, it could be, as in the case of Jonah, and it is right to examine ourselves (Job 34:32). However, it is not necessarily so, and our kind Lord would not add the burden of false guilt to our trouble (Matthew 11:29,30).

b] The Lord is with us in the storm.

“And he was in the hinder part of the ship” (4:38). In every storm, He is in the same boat with us. John Newton, who knew storms at sea as well as in life, could say,

With Christ in the vessel I smile at the storm.

And so can we because, “The LORD hath his way in the whirlwind and in the storm” (Nahum 1:3). He deals with us like this to subdue sin, draw us closer to Him, make us better Christians, and fashion us for the work of His kingdom.

c] He has power over every storm and can easily deliver us.

“And he arose, and rebuked the wind, and said unto the sea, Peace, be still. And … there was a great calm” (4:39). With His mere word our Lord stilled the storm: “Peace” spoken to the howling wind, silencing it; “Be still” to the tossing waves, calming them to a smooth surface. “The Lord of peace” is with us (2 Thessalonians 3:16). For the One who made heaven and earth no tempest is too fierce to quell (cf Psalm 107:23-31). We can be sure that, real though the storm may be, it will not be allowed to overwhelm us (Isaiah 43:1,2).

Be still, my soul: the waves and winds still know
His voice who ruled them while He dwelt below.

Now let us consider the Lord’s searching question, “Why are ye so fearful? how is it that ye have no faith?” (Mark 4:40). He means that the disciples’ reaction showed a failure of faith. If they had believed, they would not have acted the way they did; neither would they have uttered those hurtful words, “Master, carest thou not that we perish?” (verse 38).

Have we passed through stormy waters this past year? If so, how consistent has our faith been? The New Year of 2019 may bring deep and turbulent trials. One thing is sure, faith is the overcoming grace (1 John 5:4) and is always the difference between victory or defeat. According to our faith we will be brought down, or be wonderfully upheld and brought through. To help us in this, let us consider,


“How is it that ye have no faith?” Does the Lord mean they are unbelievers?

1] Not in the absolute sense.

These are disciples who have left all to follow the Master. They certainly are believers: the gift of faith is theirs (Ephesians 2:8,9; Philippians 1:29). As one of them was to write to Christians years afterwards, this indestructible grace was their treasure: “like precious faith with us” (2 Peter 1:1).

2] However, it was true in a comparative sense.

“No faith.” Our Lord means their faith was not in exercise. Matthew and Luke have, “O ye of little faith” and “Where is your faith?” These good men failed to believe what they knew to be true: that the Son of God was there with them and that all was well. They allowed the storm, and their feelings, to take them over so that they forgot Whose they were and Whom they served!

3] This can easily happen to us.

“No faith.” We fret, we panic, we go down under our circumstances. They control us, and we seem little better than unbelievers. Let us guard our reactions: the Lord has not forgotten nor abandoned us. Let us remember what we know, and reach out to Him Whom we know. Faith must not be dormant but exercised toward Him. As Thomas Watson had it: “Faith … has an eye to see Christ, as well as a wing to fly to Christ” … “Faith, though it hath sometimes a trembling hand, it must not have a withered hand, but must stretch.”

4] This was a test of faith.

It was what they saw versus what they knew was true. And, sadly, what they saw won! (2 Corinthians 5:7). It might seem that the Lord is asleep to our predicament – unaware, indifferent. But it was not so, as the sequel proved! The Lord did not need the terrified, reproachful disciples to waken Him to still the storm! He would certainly have done it.

5] Nothing troubled the Lord.

We are flummoxed and perplexed, but the Lord is not. Although asleep as Man – as God would He have allowed the boat, and them, to sink? Did He really care for these men less than they cared for themselves? Far from it. Mark tells us He was “in the hinder part of the ship” (verse 38) – this is where the helmsman steers the boat! Faith in exercise will say with George Herbert,

When winds and waves assault my keel,
He doth preserve it, He doth steer,
Ev’n when the boat seems most to reel.
Storms are the triumph of His art;
Though He may close his eyes, yet not His heart.


“How is it that ye have no faith?” What do we say to this? Why do we tend not to exercise faith when we need to most? Here are some reasons which may help us avoid this for the future.

1] Because of fear.

verse 40 “Why are ye so fearful?” The emotion of fear and the exercise of faith are opposites; and mutually exclusive. Where one is, the other cannot be. In this instance, fear pushed out faith. Therefore, before fear takes hold, remember the Lord, and do what the prophet says, “I will trust, and not be afraid” (Isaiah 12:2; cf Psalm 56:3). If you go from fear to faith, you go from fear to Him.

2] Unbelief remains in us.

It is part of the “sin that dwelleth in me” (Romans 7:17). Being our old nature, it will always make exercising faith a struggle. Every grace has its opposite corruption to oppose it. And faith has to contend against unbelief. This is why the father of the demon-possessed boy “cried out, and said with tears, Lord, I believe; help thou mine unbelief” (Mark 9:24). The encouragement, though, is that the Lord heard this man’s struggling prayer OF faith! The Lord is greater and kinder than our faltering faith.

3] We forget past deliverances.

These disciples had already seen instances of the Lord’s power. For example, the deliverance of the demoniac in the synagogue (Mark 1:23-28); Peter’s mother-in-law healed (1:30,31); many people healed, and delivered from demons (1:32-34); a leper cleansed (1;40-45); the sick of the palsy made whole (2:2-12); the man with the withered hand cured (3:1-5). For our part, we have seen His grace and goodness many times. Do we think our current storm of trouble is unique and beyond the Lord’s ability to come in for us? Having proved Him in the past, let us rise to the opportunity of proving Him in the present. Let faith go back to its Ebenezers and on to its henceforths!

4] Because faith looks beyond what is seen and temporal.

The Puritans called faith “our spiritual optic.” It enables us to see “him who is invisible” (Hebrews 11:27). Thomas Adams said, “It is the office of faith to believe what we do not see, and it shall be the reward of faith to see what we … believe.”

In this instance, however, what the disciples saw with their eyes took them over. They did not use the eye of faith that looks beyond to Him. David, too, was aware of this, “I had fainted, unless I had believed to see the goodness of the LORD in the land of the living” (Psalm 27:13). Let us look beyond and above our present distress, and believingly look to the Lord!

5] We are not enough in the Bible.

We should not underestimate our great enemy in this. Satan stirs up our carnal sense to undermine confidence in the Lord. Only God’s word can answer and silence him. As David Dickson said, “When Satan borrows sense to speak one thing, let faith borrow Scripture to speak the contrary.”

God’s word is the greatest faith-building means of grace: “faith cometh by hearing, and hearing by the word of God” (Romans 10:17). The Scriptures bring us into heart-acquaintance with Him Who is the great Object of our faith (Acts 20:32). The word of God leads us to the God of the word; it makes Him real to the soul.

Yet, when all is said, the disciples’ reaction was prayer, “they awake him and say unto him, Master, etc.” (verse 38). If at least our fear drives us to Jesus, is not all wrong. The cry to Him, even of half-believing panic, brings us His help. Their faith was weak, but their prayer was strong. The comfort is that despite His gentle question, He did not rebuke them, but the storm.

Let us humble ourselves and confess our unbelieving fears and sinful distrust. Let us pray to the Lord to increase our trust, that we might be strong in faith, and give credit and glory to God.

They never forgot this lesson. Peter especially, years afterwards wrote, correcting the unworthy reflection on the Lord, and knowing better now, “Casting all your care upon him; for he careth for you” (1 Peter 5:7).

Dear reader, believe that it will be so for you as well. We do not minimise the deep and dark trial that waves and billows can be. But as those in Psalm 107:27-30 found, they were “at their wits end,” but not at their faith’s end. Believe it is so for you as well,

… and he bringeth them out of their distresses. He maketh the storm a calm, so that the waves thereof are still. Then are they glad because they be quiet; so he bringeth them unto their desired haven.

And that haven is into His arms, upon His bosom – to be safer in the storm with Him than in the calm without Him.

The storm may roar without me,
My heart may low be laid;
But God is round about me,
And can I be dismayed?

by Rev. John Thackway, Pastor of Holywell Evangelical Church

Used with kind permission of the author

Friday, 1 February 2019

Myalgic Encephalomyelitis: A Baffling Syndrome With A Tragic Aftermath

[This article by Dr Melvin Ramsay (1901 – 1990) was first published in 1986. I thought that it would be helpful, with all the current confusion about ME and mixing it up with various fatigue syndromes and states, to reproduce it here.]

Myalgic Encephalomyelitis: A Baffling Syndrome With A Tragic Aftermath


Melvin Ramsay, M.A., M.D. Hon Consultant Physician,

Infectious diseases Department, Royal Free Hospital

Myalgic Encephalomyelitis leaves a chronic aftermath of debility in a large number of cases. The degree of physical incapacity varies greatly, but the dominant clinical feature of profound [paralytic muscle] fatigue is directly related to the length of time the patient persists in physical effort after its onset; put in another way, those patients who are given a period of enforced rest from the onset have the best prognosis.

Although the onset of the disease may be sudden and without apparent cause, as in those whose first intimation of illness is an alarming attack of acute vertigo, there is practically always a history of recent virus infection associated with upper respiratory tract symptoms though occasionally there is gastro-intestinal upset with nausea and vomiting. Instead of making a normal recovery, the patient is dogged by persistent profound fatigue accompanied by a medley of symptoms such as headache, attacks of giddiness, neck pain, muscle weakness, parasthesiae, frequency of micturition or retention, blurred vision and/or diplopia and a general sense of 'feeling awful'. Many patients report the occurrence of fainting attacks which abate after a small meal or even a biscuit, and in an outbreak in Finchley, London, in 1964 three patients were admitted to hospital in an unconscious state presumably as a result of acute hypoglycaemia. There is usually a low-grade pyrexia [fever] which quickly subsides. Respiratory symptoms such as sore throat tend to persist or recur at intervals. Routine physical examination and the ordinary run of laboratory investigations usually prove negative and the patient is then often referred for psychiatric opinion. In my experience this seldom proves helpful is often harmful; it is a fact that a few psychiatrists have referred the patient back with a note saying 'this patient's problem does not come within my field'. Nevertheless, by this time the unfortunate patient has acquired the label of 'neurosis' or 'personality disorder' and may be regarded by both doctor and relatives as a chronic nuisance. We have records of three patients in whom the disbelief of their doctors and relatives led to suicide; one of these was a young man of 22 years of age.

The too facile assumption that such an entity - despite a long series of cases extending over several decades - can be attributed to psychological stress is simply untenable. Although the aetiological factor or factors have yet to be established, there are good grounds for postulating that persistent virus infection could be responsible. It is fully accepted that viruses such as herpes simplex and varicella-zoster remain in the tissues from the time of the initial invasion and can be isolated from nerve ganglia post-mortem; to these may be added measles virus, the persistence of which is responsible for subacute sclerosing panencephalitis that may appear several years after the attack and there is a considerable body of circumstantial evidence associating the virus with multiple sclerosis. There should surely be no difficulty in considering the possibility that other viruses may also persist in the tissues. In recent years routine antibody tests on patients suffering from myalgic encephalomyelitis have shown raised titres to Cocksackie B Group viruses. It is fully established that these viruses are the aetiological agents of 'Epidemic Myalgia' or 'Bornholm's Disease' and that, together with ECHO viruses, they comprise the commonest known virus invaders of the central nervous system. This must not be taken to imply that Cocksackie viruses are the sole agents of myalgic encephalomyelitis since any generalised virus infection may be followed by a period of post-viral debility. Indeed, the particular invading microbial agent is probably not the most important factor. Recent work suggests that the key to the problem is likely to be found in the abnormal immunological response of the patient to the organism.

A second group of clinical features found in patients suffering from myalgic encephalomyelitis would seem to indicate circulatory disorder. Practically without exception they complain of coldness in the extremities and many are found to have abnormally low temperatures of 94 or 95 degrees F. In a few, these are accompanied by bouts of severe sweating even to the extent of waking during the night lying in a pool of water. A ghostly facial pallor is a well known phenomenom and this has often been detected by relatives some 30 minutes before the patient complains of being ill.

The third component of the diagnostic triad of myalgic encephalomyelitis relates to cerebral activity. Impairment of memory and inability to concentrate are features in every case. Many report difficulty in saying the right word and are conscious of the fact that they continue to say the wrong one, for example 'cold' when they mean 'hot'. Others find that they start a sentence but cannot complete it, while some others have difficulty comprehending the written or spoken word. A complaint of acute hyperacusis is not infrequent; this can be quite intolerable but alternates with periods of normal hearing or actual deafness. Vivid dreams generally in colour are reported by persons with no previous experience of such a phenomenon. Emotional lability is often a feature in a person of previous stable personality, while sudden bouts of uncontrollable weeping may occur. Impairment of judgement and insight in severe cases completes the 'encephalitic' component of the syndrome.

I would like to suggest that in all patients suffering from chronic debility for which a satisfactory explanation is not forthcoming a renewed and much closer appraisal of their symptoms should be made. This applies particularly to the dominant clinical feature of profound fatigue. While it is true that there is considerable variation in degree from one day to the next or from one time of the day to another, nevertheless in those patients whose dynamic or conscientious temperaments urge them to continue effort despite profound malaise or in those who, on the false assumption of 'neurosis', have been exhorted to 'snap out of it' and 'take plenty of exercise' the condition finally results in a state of constant exhaustion. This has been amply borne out by a series of painstaking and meticulous studies carried out by a consultant in physical medicine, himself an ME sufferer for 25 years. These show clearly that recovery of muscle power after exertion is unduly prolonged. After moderate exercise, from which a normal person would recover with nothing more than a good night's rest, an ME patient will require at least 2 to 3 days while after more strenuous exercise the period can be prolonged to 2 or 3 weeks or more. Moreover, if during this recovery phase, there is a further expenditure of energy the effect is cumulative and this is responsible for the unrelieved sense of exhaustion and depression which characterises the chronic case. The greatest degree of muscle weakness is likely to be found in those muscles which are most in use; thus in right- handed persons the muscles of the left hand and arm are found to be stronger than those on the right. Muscle weakness is almost certainly responsible for the delay in accommodation which gives rise to blurred vision and for the characteristic feature of all chronic cases, namely a proneness to drop articles altogether with clumsiness in performing quite simple manoeuvres; the constant dribbling of saliva which is also a feature of chronic cases is due to weakness of the masseter muscles. In some cases, the myalgic element is obvious but in others a careful palpitation of all muscles will often reveal unsuspected minute foci of acute tenderness; these are to be found particularly in the trapezii, gastrocnemii and abdominal rectii muscles.

The clinical picture of myalgic encephalomyelitis has much in common with that of multiple sclerosis but, unlike the latter, the disease is not progressive and the prognosis should therefore be relatively good. However, this is largely dependent on the management of the patient in the early stages of the illness. Those who are given complete rest from the onset do well and this was illustrated by the aforementioned three patients admitted to hospital in an unconscious state; all three recovered completely. Those whose circumstances make adequate rest periods impossible are at a distinct disadvantage, but no effort should be spared to give them the all-essential basis for successful treatment. Since the limitations which the disease imposes vary considerably from case to case, the responsibility for determining these rests upon the patient. Once these are ascertained the patient is advised to fashion a pattern of living that comes well within them. Any excessive physical or mental stress is likely to precipitate a relapse.

It can be said that a long-term research project into the cause of the disease has been launched and there are good grounds for believing that this will demonstrate beyond doubt that the condition is organically determined.