Mari, 34 years old, began to notice that her left eyelid drooped more towards the end of the day and that, after reading for a while, her vision became blurred and doubled. At first, she thought it was just accumulated fatigue. Weeks later, she felt her arms weaker when combing her hair and sought out a neurologist. Mari's case helps us understand how myasthenia gravis typically appears in the lives of those diagnosed with it.

What is myasthenia gravis

Myasthenia gravis is an autoimmune disease that affects the neuromuscular junction, the point of contact between the nerve and the muscle through which the command passes for the muscle to contract. When this communication fails, the muscle receives the signal incompletely and becomes fatigued much faster than it should.

What it means to be an autoimmune disease

The immune system exists to recognise and attack what is foreign to the body, such as viruses and bacteria. In an autoimmune disease, this defence system misses its target and begins to produce antibodies against structures of the body itself. In myasthenia gravis, these antibodies mainly attack the acetylcholine receptors, a substance responsible for transmitting the signal from the nerve to the muscle. The practical result is similar: the nerve signal reaches the muscle in a weakened form.

Symptoms and how the clinical presentation occurs

The hallmark of myasthenia gravis is fluctuating weakness: it worsens with repeated muscle use throughout the day and improves with rest. The most common signs include:

  • drooping eyelid (ptosis), which may affect one or both eyes, usually more evident in the afternoon or evening
  • double vision (diplopia)
  • difficulty chewing or swallowing, and more frequent choking during meals
  • speech that becomes slurred or hyponasal after talking for a while
  • weakness in the arms, legs or neck, which makes it difficult to raise the arms above the head, climb stairs or hold the head up
  • in more advanced cases, weakness of the muscles that help with breathing

In about half to two-thirds of people, the first symptoms appear in the eyes (ocular myasthenia). In a good proportion of these cases, the disease progresses to the generalised form, affecting other muscle groups, within one to three years.

Risk factors

Myasthenia gravis can appear at any age, including in childhood, but follows a known pattern: it is more common in young women, between 20 and 40 years of age, and in older men, between 50 and 80 years of age. Other factors associated with increased risk are:

  • presence of thymoma (a tumour, usually benign, in the thymus gland) or thymus enlargement
  • having another autoimmune disease, such as thyroid problems or lupus, which indicates a greater tendency of the immune system to react against the body itself
  • genetic variations linked to the immune system (HLA genes), which increase predisposition without, however, making the disease hereditary in the direct sense

Is the person born with the disease or does it develop over time

Autoimmune myasthenia gravis is not a condition with which a person is born. It develops over time, usually gradually, over weeks or months, when the immune system begins to produce antibodies that attack the neuromuscular junction. The exact reasons that trigger this process are not yet fully known, but involve a combination of genetic predisposition with some environmental trigger, such as infections.

It is important not to confuse this form with congenital myasthenic syndromes, a group of rare diseases of genetic origin, present from birth and which have no relation to the immune system. There is also a temporary form called transient neonatal myasthenia, which can occur in babies of mothers with myasthenia gravis, because maternal antibodies cross the placenta, but usually disappears within a few weeks.

Once established, myasthenia gravis usually follows a fluctuating course, with periods of worsening and improvement, and tends to be a long-term condition, monitored throughout life.

Is it possible to prevent the development of the disease

At present, there is no proven way to prevent myasthenia gravis, as its causes involve a combination of genetic and immunological factors that are still being studied. It is not linked to lifestyle habits, diet or exposures that can be directly avoided. Therefore, the most important thing is to recognise the signs early and seek medical evaluation as soon as symptoms such as drooping eyelid, double vision or fluctuating weakness appear, which allows treatment to be started sooner.

Treatment

Treatment is individualised and monitored by a neurologist, and combines different strategies according to severity:

  • pyridostigmine, a medication that improves signal transmission between nerve and muscle, is usually the first step and relieves symptoms in everyday life
  • corticosteroids and immunosuppressants, such as azathioprine or mycophenolate, work by controlling the exaggerated immune response
  • intravenous immunoglobulin and plasmapheresis are used in crises or in more severe cases, as they rapidly remove or neutralise circulating antibodies
  • thymectomy, surgery to remove the thymus, is indicated when there is a thymoma and is also considered in younger people with the generalised form of the disease, since studies show that it can reduce the need for immunosuppressants in the long term
  • in recent years, new classes of medications have greatly expanded options for those who do not respond well to traditional treatments: FcRn receptor blockers (such as efgartigimod, rozanolixizumab and nipocalimab), which accelerate the elimination of antibodies causing the disease, and complement inhibitors (such as eculizumab, ravulizumab and zilucoplan), which block a step in the immune response that damages the neuromuscular junction. Therapies that reduce antibody-producing defence cells are also increasingly in use.

There is still no definitive cure, but with appropriate treatment most people with myasthenia gravis are able to maintain an active life, with symptoms well controlled.

When to seek immediate medical attention

There is an emergency situation called myasthenic crisis, in which weakness affects the muscles of respiration and swallowing significantly. The warning signs that require immediate emergency room attendance include:

  • shortness of breath or sensation of shallow, short breathing
  • significant difficulty swallowing, with risk of choking
  • very weak, slurred or almost inaudible speech
  • rapid and progressive worsening of weakness within a few hours

In these situations, respiratory support and hospital treatment may be necessary until the condition stabilises. It is also worth remembering that certain infections, situations of physical stress and certain medications (some antibiotics and anaesthetics, for example) can worsen symptoms, so anyone with this diagnosis should always inform any health professional of this condition before starting a new treatment.

This content is educational and informative in nature. It does not replace consultation, diagnosis or treatment with a qualified health professional. Should you experience symptoms suggestive of myasthenia gravis, seek medical evaluation.

Dr Rebeca Soares Andrade CRM - GO 39335