Myasthenia gravis

Myasthenia gravis is not a disease of the muscle itself but of the point where the nerve hands over its instruction. The immune system mistakenly blocks the receivers that pick up that signal on the muscle fibre, and part of the instruction never arrives. The fibre is healthy, so the strength is there — it just runs out quickly: the longer the muscle works, the weaker it gets, and rest brings the strength back. Because of that swing, the illness is put down to tiredness, age or nerves for years. It still cannot be cured, but modern treatment returns most people to an ordinary life.

How it starts: eyelids and gaze

In roughly two people out of three the eye muscles give way first. A lid droops, one more than the other, and more by the evening than in the morning. Things appear double: two edges to a doorway, two lines of text, two oncoming cars. The double image disappears if you close one eye and comes back after a few minutes of reading.

This is where the hallmark of the illness already shows: weakness builds with use and eases with rest. A person wakes almost well, speaks through the nose by lunchtime and struggles to lift their arms by evening. No two days are alike, and that is not fussiness — it is how the disease works.

The face loses expression and the smile comes out strained, more of a snarl. Sensation is untouched: numbness, pins and needles or pain as the main complaint are not typical of myasthenia, and the pupils react normally. If only the eyes are involved and nothing has spread in two years, it will most likely stay that way.

When the weakness spreads

In most people the weakness leaves the eyes within the first months or years. The muscles of speech, chewing and swallowing usually go next.

• The voice fades towards the end of a conversation, becoming quiet and nasal, as if it came through the nose, and the words slur.
• Chewing is hard by the middle of a meal and the jaw has to be propped up with a hand; tough meat and crusty bread become a trial.
• The person chokes, liquid goes up the nose and food seems to stick; hence repeated chest infections and weight loss.
• The head grows heavy and falls forward, and you want to support it with your hand.

In the limbs the weakness is greater close to the trunk and more obvious in the arms than the legs: it is hard to comb your hair, hang out washing, reach a shelf or get out of a chair without pushing up. The walk becomes a waddle. Muscles may ache after use, but the leading complaint is not pain — it is that the movement runs out.

Breathing deserves a mention of its own. Breathlessness on the stairs, tightness when lying flat, the need to sleep propped up and a cough that has lost its force are weakness of the breathing muscles, and that is not something to sit on.

Why the signal fails to reach the muscle

Myasthenia gravis is an autoimmune illness. Antibodies settle on the receptors that take the signal from the nerve and stop them working. Most often these are antibodies to the acetylcholine receptor; less often they are directed against a protein called MuSK, and in that form the face, speech and swallowing suffer more.

The illness is closely tied to the thymus, a small organ in the chest where immune cells are trained. In many patients it is still large when by adulthood it should have shrunk, and in about one in ten a tumour called a thymoma is found in it. That is why the chest is always examined.

Some variants must not be mistaken for ordinary myasthenia. In a baby born to a mother with the condition, antibodies can cross the placenta: the newborn feeds feebly and cries weakly for the first weeks, and then it passes by itself. Congenital myasthenic syndromes are not autoimmune but genetic, begin in childhood and do not respond to drugs that damp down the immune system. Most important of all, a similar weakness is produced by Lambert-Eaton syndrome, which in smokers is often the first sign of lung cancer. The details help tell them apart: strength briefly improves after repeating a movement, the mouth is dry, the knee reflexes cannot be obtained and the eyes are barely involved. Such a patient needs the tumour looked for, not just the weakness treated.

How the diagnosis is confirmed

The diagnosis rests on three pieces: weakness that fluctuates, antibodies in the blood, and the failure of transmission that electromyography shows.

• A blood test for antibodies to the acetylcholine receptor is the main investigation. It is positive in about eight in ten people with the generalised form and in only half of the ocular ones. If it is negative, anti-MuSK antibodies are looked for.
• Nerve conduction studies with repetitive stimulation: in myasthenia the muscle response fades over a train of impulses. The most sensitive version is single-fibre electromyography.
• A CT scan of the chest is essential so that a thymoma is not missed.
• The ice pack test for a drooping lid: two minutes of cold and the lid lifts.
• The thyroid is checked at the same time, as it not uncommonly misbehaves in the same people.

It is worth knowing what does not find myasthenia: the routine blood count, the biochemistry, an X-ray and an MRI scan of the brain are all normal in this condition. A normal MRI does not remove the diagnosis; it only rules out other causes. The edrophonium test is now barely used, because it can slow the heart sharply, and it is done only in hospital.

What upsets the balance

Even on well-adjusted treatment things can deteriorate suddenly, and there is nearly always a reason.

• Infection, from flu or covid to a simple sore throat; a fever in myasthenia is not something to sit out at home.
• Heat, a hot bath, a sauna, the fever itself.
• Too little sleep, heavy physical effort, severe stress.
• An operation and anaesthesia, childbirth and the weeks after it.
• Stopping or missing medication on your own, and reducing the steroid dose too fast.

The most underrated cause is medicines. Myasthenia can be worsened by some groups of antibiotics (aminoglycosides, fluoroquinolones, macrolides), by magnesium given by injection or drip, by beta blockers, by some drugs for heart rhythm, by quinine, by botulinum toxin, by certain drugs for rheumatic disease and by cancer immunotherapy. This is not a ban: many of them are given under supervision when they are needed. But the doctor prescribing something new, the dentist and the anaesthetist all need to know the diagnosis before the decision, not after. It is worth carrying a card that states it.

When to call an ambulance

A rapid decline in breathing and swallowing is called a myasthenic crisis, and it is dealt with only in hospital. Do not delay calling an ambulance (in most European countries, 112) if there is:

• breathlessness at rest, fast shallow breathing, an inability to lie flat;
• speech in bursts of two or three words, because the breath does not last a sentence;
• a weak cough, an inability to clear the throat and choking on saliva;
• a head that will not stay up and weakness increasing over hours;
• blue lips, confusion or unusual drowsiness.

See a doctor the same day if a fever develops, if swallowing has become clearly worse than a week ago, if weakness jumped after starting a new medicine, or if tablets can no longer be taken by mouth. A separate situation is too much of the drug that improves transmission: stomach cramps, diarrhoea, heavy saliva and sweating, small pupils and, alongside all that, more weakness. Working out on your own whether there is too little medicine or too much is impossible, and guessing at the dose in that moment is dangerous.

What treatment offers

Treatment runs along two lines: improving transmission here and now, and turning down the immune process itself.

• Pyridostigmine makes the signal at the muscle last longer and lifts the weakness for a few hours, so it is taken several times a day and timed around meals and tasks. In mild disease that is often enough. Side effects are stomach cramps, diarrhoea, muscle twitching and salivation.
• Steroids reduce antibody production and work for most people. The dose is built up gradually: with a fast start the weakness can briefly increase in the first weeks. Long-term use brings weight gain, fragile bones and a rise in blood sugar and blood pressure, so the dose is later brought down to the lowest that holds.
• Drugs that damp the immune system — azathioprine, mycophenolate, methotrexate — allow high steroid doses to be left behind. They take months to work, need regular blood tests and raise the risk of infection.
• In stubborn disease rituximab is used, particularly with anti-MuSK antibodies, along with targeted drugs: complement inhibitors and agents that speed the clearance of the harmful antibodies from the blood.
• Thymectomy is removal of the thymus, usually through small incisions. With a thymoma it is removed in any case, as any tumour would be. In generalised disease with receptor antibodies, and in people who are not elderly, the operation reduces the need for medication, though the benefit unfolds over months.
• In a crisis and before surgery, plasma exchange or intravenous immunoglobulin is used: they strip out the antibodies within days, but not for long.

Arranging the day

Half the result lies not in the tablets but in the timetable. Anything that matters is planned for the morning and for the hours when the medicine is working. Rest is taken before the strength runs out: a short sleep in the day restores more than pushing through does.

For double vision it helps to cover one lens of your glasses or to alternate a patch between the right and left eye; persistent double vision and a drooping lid are corrected with prisms, a lid support or surgery, but only once things have been stable for a year. Nobody should drive while seeing double.

Food is made softer and portions smaller, and meals are placed at the peak of the tablet's effect. It is better to eat sitting upright, without talking and without tipping the head back; where swallowing is badly affected, a speech and language therapist works out a safe consistency.

Flu and pneumococcal vaccination make sense for almost everyone, while live vaccines are discussed in advance if immune-suppressing drugs are being taken. Pregnancy is possible but is planned with the neurologist, since some medicines are changed before conception.

Online consultation

An online appointment is useful while there is still no diagnosis: the doctor can judge whether this shifting weakness fits myasthenia and say which blood tests and which nerve study are worth arranging, so that you are not sent in circles between specialists. Once the diagnosis is made, the doctor explains the hospital letter in plain words, helps spread pyridostigmine across the day, checks that the chest has been imaged and considers whether a recent deterioration is linked to a new medicine.

Have your letters ready for the appointment, along with the antibody and electromyography results, a list of medicines with doses, and a week of notes: what time of day the weakness is worst and what made it worse. An online consultation does not replace a face-to-face neurological examination. If breathlessness is increasing, if there is choking and the cough is weak, that needs urgent care in person rather than a message.

This material is for information only and does not replace medical advice.